67 results on '"Aspasia Stamatoullas"'
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2. Complete hematologic response after belinostat treatment and allogeneic stem cell transplantation for multiple relapsed/refractory angioimmunoblastic T‐cell lymphoma: A case report
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Vincent Camus, Pascaline Etancelin, Fanny Drieux, Elena‐Liana Veresezan, Jean‐Michel Picquenot, Dominique Penther, Mathieu Viennot, Philippe Ruminy, Nathalie Contentin, Emilie Lemasle, Stéphane Leprêtre, Sydney Dubois, Juliette Penichoux, Aspasia Stamatoullas, Alexandra Zduniak, Hélène Lanic, and Fabrice Jardin
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allogenic stem cell transplantation ,belinostat ,complete response ,HDAC inhibitor ,nTFHL‐AI ,PTCL ,Medicine ,Medicine (General) ,R5-920 - Abstract
Key Clinical Message This case report highlights the potential of belinostat for the treatment of relapsed/refractory peripheral T‐cell lymphomas, for which effective therapies are still scarce. Abstract Peripheral T‐cell lymphomas have an aggressive disease course associated with poor outcomes. We report a young patient with highly pretreated relapsed/refractory nodal follicular helper T‐cell lymphoma (angioimmunoblastic‐type [nTFHL‐AI]), who successfully received an allogeneic stem cell transplantation following belinostat therapy. The complete hematologic response achieved has lasted more than 2 years.
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- 2023
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3. Prognostic value of baseline metabolic tumour volume in advanced-stage Hodgkin’s lymphoma
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Pierre Pinochet, Edgar Texte, Aspasia Stamatoullas-Bastard, Pierre Vera, Sorina-Dana Mihailescu, and Stéphanie Becker
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Medicine ,Science - Abstract
Abstract Our aim was to evaluate the prognostic value of initial total metabolic tumour volume (TMTV) in a population of patients with advanced-stage Hodgkin’s lymphoma (HL). We retrospectively included 179 patients with stage IIb-III-IV Hodgkin’s disease who received BEACOPP or ABVD as the first-line treatment. The initial TMTV was determined using a semi-automatic method for each patient. We analysed its prognostic value in terms of 5-year progression-free survival (PFS), overall survival, and positron emission tomography (PET) response after two courses of chemotherapy. Considering all the treatments and using a threshold of 217 cm3, TMTV was predictive of 5-year PFS and PET response after two courses of chemotherapy. In multivariable analysis involving TMTV, IPI score, and the first treatment received, TMTV remained a baseline prognostic factor for 5-year PFS. In the subgroup of patients treated with BEACOPP with a threshold of 331 cm3, TMTV was predictive of PET response, but not 5-year PFS (p = 0.087). The combined analysis of TMTV and PET response enabled the individualisation of a subgroup of patients (low TMTV and complete response on PET) with a very low risk of recurrence. Baseline TMTV appears to be a useful independent prognostic factor for predicting relapse in advanced-stage HL in ABVD subgroup, with a tendency of survival curves separation in BEACOPP subgroup.
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- 2021
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4. Relapsed and refractory classical Hodgkin lymphoma: could virotherapy help solve the equation?
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Selma Addou, Clémentine Sarkozy, Julien Lazarovici, Stéphane Champiat, Aspasia Stamatoullas, Fabrice Jardin, Vincent Ribrag, Aurélien Marabelle, and Jean-Marie Michot
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hodgkin lymphoma ,virotherapy ,oncolytic viruses ,epstein-barr virus ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Classical Hodgkin lymphoma is a neoplastic hematological disease. Standard first-line therapy, including chemotherapy and radiotherapy, is curative in >85% of early-stage patients, with a 5-year survival rate of >95%. However, approximately 15% of patients have hard-to-treat lymphoma with poor outcomes, and new treatment strategies are needed for these young adults. There are several well-documented cases in the medical literature on hematologic cancer remission following natural human viral infections. Therefore, hoping to reproduce these spontaneous tumor regressions, researchers have been investigating various viruses with oncolytic properties. There is a high rationale for using virotherapy in the treatment of Hodgkin lymphoma, in which tumor cells are often infected with the Epstein-Barr virus. Modern viral technologies and current knowledge about the relationship between viruses and cancer could accelerate the discovery of effective viral oncolytic therapies. This article reviews the use of oncolytic viruses as innovative therapies for treating Hodgkin lymphoma.
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- 2021
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5. Successful treatment of severe post hematopoietic stem cell transplantation bronchiolitis obliterans syndrome with lung transplantation in a patient with multi‐organ chronic graft‐versus‐host disease
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Juliette Pénichoux, Florian Bouclet, Mustafa Alani, Nathalie Contentin, Anne‐Lise Ménard, Stéphane Leprêtre, Pascal Lenain, Aspasia Stamatoullas, Elodie Lhuillier, Hélène Lanic, Emilie Lemasle, Sydney Dubois, Jean‐Henri Bourhis, Hervé Mal, Fabrice Jardin, and Vincent Camus
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allogeneic hematopoietic stem cell transplantation ,bronchiolitis obliterans syndrome ,graft‐versus‐host disease ,Medicine ,Medicine (General) ,R5-920 - Abstract
Abstract Allogeneic stem cell transplant and chronic graft‐versus‐host disease may lead to severe non‐infectious pulmonary disease in 6% of patients at 5 years. We report the case of a young patient with acute myeloid leukemia who successfully received bilateral lung transplantation for severe bronchiolitis obliterans syndrome.
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- 2022
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6. High-risk stage IIB Hodgkin lymphoma treated in the H10 and AHL2011 trials: total metabolic tumor volume is a useful risk factor to stratify patients at baseline
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Cédric Rossi, Marc André, Jehan Dupuis, Franck Morschhauser, Bertrand Joly, Julien Lazarovici, Hervé Ghesquières, Aspasia Stamatoullas, Emmanuelle Nicolas-Virelizier, Pierre Feugier, Anne-Claire Gac, Hannah Moatti, Luc-Matthieu Fornecker, Bénédicte Deau, Clémentine Joubert, Catherine Fortpied, John Raemaekers, Massimo Federico, Salim Kanoun, Michel Meignan, Alexandra Traverse-Glehen, Anne-Ségolène Cottereau, and René-Olivier Casasnova
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Stage IIB Hodgkin lymphoma (HL) patients, with a mediastinum-to-thorax (M/T) ratio of ≥0.33 or extranodal localization have a poor prognosis and are treated either as limited or advanced stage. We compared these two approaches in patients included in two randomized phase III trials enrolling previously untreated early (H10) or advanced stage HL (AHL2011). We included HL patients with Ann-Arbor stage IIB with M/T ≥0.33 or extranodal involvement enrolled in the H10 or AHL2011 trials with available positron emission tomography at baseline (PET0) and after two cycles of chemotherapy (PET2). Baseline total metabolic tumor volume (TMTV) was calculated using the 41% SUVmax method. PET2 response assessment used the Deauville score. One hundred and fourty-eight patients were eligible, including 83 enrolled in the AHL2011 trial and 65 in the H10 trial. The median TMTV value was 155.5 mL (range, 8.3-782.9 mL), 165.6 mL in AHL2011 and 147 mL in H10. PET2 positivity rates were 16.9% (n=14) and 9.2% (n=6) in AHL2011 and H10 patients, respectively. With a median follow-up of 4.1 years (95% confidence interval [CI]: 3.9-4.4), overall 4-year PFS was 88.0%, 87.0% in AHL2011 and 89.2% in H10. In univariate and mutivariate analyses, baseline TMTV and PET2 response influenced significantly progression-free survival (hazard ratio [HR]=4.94, HR=3.49 respectively). Notably, among the 16 patients who relapsed, 13 (81%) had a baseline TMTV baseline ≥155 mL. Upfront ABVD plus radiation therapy or upfront escBEACOPP without radiotherapy provide similar patient’s outcome in high-risk stage IIB HL. TMTV is useful to stratify these patients at baseline.
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- 2022
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7. Multiple cutaneous ulcers revealing a primary cutaneous Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma
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Billal Tedbirt, Sydney Dubois, Lucie Cellier, Priscille Carvalho, Aspasia Stamatoullas, Philippe Courville, Aurélie Deschamps‐Huvier, Pascaline Etancelin, Anne Deniel, Hervé Tilly, Fabrice Jardin, Pascal Joly, and Vincent Camus
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cutaneous lymphoma ,cutaneous ulcers ,Epstein‐Barr virus ,Medicine ,Medicine (General) ,R5-920 - Abstract
Abstract Primary cutaneous EBV‐positive diffuse large B‐cell lymphoma is an exceptional and aggressive neoplasia with a poorer prognosis than other cutaneous lymphoma. Our observation points out the rarity of the presentation and the dismal clinical course.
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- 2020
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8. Outcomes of refractory or relapsed Hodgkin lymphoma patients with post-autologous stem cell transplantation brentuximab vedotin maintenance: a French multicenter observational cohort study
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Amira Marouf, Anne Segolene Cottereau, Salim Kanoun, Paul Deschamps, Michel Meignan, Patricia Franchi, David Sibon, Clara Antoine, Thomas Gastinne, Cecile Borel, Mohammad Hammoud, Guillaume Sicard, Romane Gille, Doriane Cavalieri, Aspasia Stamatoullas, Lauriane Filliatre-Clement, Julien Lazarovici, Adrien Chauchet, Luc-Matthieu Fornecker, Sandy Amorin, Mathieu Rocquet, Nicole Raus, Barbara Burroni, Marie Therese Rubio, Didier Bouscary, Philippe Quittet, Rene Olivier Casasnovas, Pauline Brice, Herve Ghesquieres, Jérôme Tamburini, and Benedicte Deau
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2021
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9. Dissociated humoral and cellular immune responses after a three-dose schema of BNT162b2 vaccine in patients receiving anti-CD20 monoclonal antibody maintenance treatment for B-cell lymphomas
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Sophie Candon, Veronique Lemee, Emilie Leveque, Pascaline Etancelin, Cedric Paquin, Marion Carette, Nathalie Contentin, Victor Bobee, Mustafa Alani, Nathalie Cardinael, Stephane Lepretre, Vincent Camus, Florian Bouclet, Edwige Boulet, Anne-Lise Menard, Helene Lanic, Aspasia Stamatoullas, Emilie Lemasle, Louis-Ferdinand Pepin, Doriane Richard, Sydney Dubois, Herve Tilly, Alain Dalleac, Jean-Christophe Plantier, Manuel Etienne, and Fabrice Jardin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2021
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10. Fatigue level changes with time in long-term Hodgkin and non-Hodgkin lymphoma survivors: a joint EORTC-LYSA cross-sectional study
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Raphaël Busson, Marleen van der Kaaij, Nicolas Mounier, Berthe M. P. Aleman, Catherine Thiéblemont, Aspasia Stamatoullas, Vincent Ribrag, Hervé Tilly, Corinne Haioun, René-Olivier Casasnovas, Hanneke C. Kluin-Nelemans, and Michel Henry-Amar
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Hodgkin lymphoma ,Non-Hodgkin lymphomas ,Long-term survivors ,Fatigue ,Cross-sectional study ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background Long-term lymphoma survivors often complain of persistent fatigue that remains unexplained. While largely reported in Hodgkin lymphoma (HL), long-term fatigue is poorly documented in non-Hodgkin lymphomas (NHL). Data collected in two cohort studies were used to illustrate the fatigue level changes with time in the two populations. Methods Two cross-sectional studies were conducted in 2009–2010 (HL) and in 2015 (NHL) in survivors enrolled in European Organisation for Research and Treatment of Cancer (EORTC) Lymphoma Group and Lymphoma Study Association (LYSA) trials. The same protocol and questionnaires were used in both studies including the Multidimensional Fatigue Inventory (MFI) tool to assess fatigue and a checklist of health disorders. Multivariate linear regression models were used in the two populations separately to assess the influence of time since diagnosis and primary treatment, age, gender, education level, cohabitation status, obesity and health disorders on fatigue level changes. Fatigue level changes were compared to general population data. Results Overall, data of 2023 HL and 1619 NHL survivors with fatigue assessment available (99 and 97% of cases, respectively) were analyzed. Crude levels of fatigue were similar in the two populations. Individuals who reported health disorders (61% of HL and 64% of NHL) displayed higher levels of fatigue than those who did not (P
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- 2019
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11. Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study
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Vincent Camus, Mathieu Viennot, Justine Lequesne, Pierre-Julien Viailly, Elodie Bohers, Lucile Bessi, Bénédicte Marcq, Pascaline Etancelin, Sydney Dubois, Jean-Michel Picquenot, Elena-Liana Veresezan, Marie Cornic, Lucie Burel, Justine Loret, Stéphanie Becker, Pierre Decazes, Pascal Lenain, Stéphane Lepretre, Emilie Lemasle, Hélène Lanic, Anne-Lise Ménard, Nathalie Contentin, Hervé Tilly, Aspasia Stamatoullas, and Fabrice Jardin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients] were assessed in this non-interventional study. Median age of the patients was 33.5 years (range 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype are correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, NA=6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). Mean of DeltaSUVmax after C2 was -78.8%. We analyzed ctDNA after C2 for 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.
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- 2020
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12. A phase II study of guadecitabine in higher-risk myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure
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Marie Sébert, Aline Renneville, Cécile Bally, Pierre Peterlin, Odile Beyne-Rauzy, Laurence Legros, Marie-Pierre Gourin, Laurence Sanhes, Eric Wattel, Emmanuel Gyan, Sophie Park, Aspasia Stamatoullas, Anne Banos, Kamel Laribi, Simone Jueliger, Luke Bevan, Fatiha Chermat, Rosa Sapena, Olivier Nibourel, Cendrine Chaffaut, Sylvie Chevret, Claude Preudhomme, Lionel Adès, and Pierre Fenaux
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years [Interquartile Range (IQR) 69-76]. Fifty-five patients received at least one cycle of guadecitabine (60 mg/m2/d subcutaneously days 1-5 per 28-day treatment cycles), with a median of 3 cycles (range, 0-27). Eight (14.3%) patients responded, including two complete responses; median response duration was 11.5 months. Having no or few identified somatic mutations was the only factor predicting response (P=0.035). None of the 11 patients with TP53 mutation responded. Median overall survival was 7.1 months, and 17.9 months in responders (3 of whom had overall survival >2 years). In multivariate analysis, IPSS-R (revised International Prognostic Scoring System) score other than very high (P=0.03) primary versus secondary azacitidine failure (P=0.01) and a high rate of demethylation in blood during the first cycle of treatment (P=0.03) were associated with longer survival. Thus, guadecitabine can be effective, sometimes yielding relatively prolonged survival, in a small proportion of high-risk myelodysplastic syndrome/low blast count acute myeloid leukemia patients who failed azacitidine. (Trial registered at clinicaltrials.gov identifier: 02197676)
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- 2019
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13. A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma
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Eric Van Den Neste, Marc André, Thomas Gastinne, Aspasia Stamatoullas, Corinne Haioun, Amine Belhabri, Oumedaly Reman, Olivier Casasnovas, Hervé Ghesquieres, Gregor Verhoef, Marie-José Claessen, Hélène A. Poirel, Marie-Christine Copin, Romain Dubois, Peter Vandenberghe, Ioanna-Andrea Stoian, Anne S. Cottereau, Sarah Bailly, Laurent Knoops, and Franck Morschhauser
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in patients with relapsed/refractory Hodgkin lymphoma. The primary objective was overall response rate according to the International Harmonization Project 2007 criteria. Thirty-three patients with advanced disease (median number of prior lines of treatment: 5; refractory: 82%) were included; nine (27.3%) received at least six cycles of ruxolitinib and six (18.2%) received more than six cycles. The overall response rate after six cycles was 9.4% (3/32 patients). All three responders had partial responses; another 11 patients had transient stable disease. Best overall response rate was 18.8% (6/32 patients). Rapid alleviation of B-symptoms was common. The median duration of response was 7.7 months, median progression-free survival 3.5 months (95% CI: 1.9–4.6), and the median overall survival 27.1 months (95% CI: 14.4–27.1). Forty adverse events were reported in 14/33 patients (42.4%). One event led to treatment discontinuation, while 87.5% of patients recovered without sequelae. Twenty-five adverse events were grade 3 or higher. These events were mostly anemia (n=11), all considered related to ruxolitinib. Other main causes of grade 3 or higher adverse events included lymphopenia and infections. Of note, no cases of grade 4 neutropenia or thrombocytopenia were observed. Ruxolitinib shows signs of activity, albeit short-lived, beyond a simple anti-inflammatory effect. Its limited toxicity suggests that it has the potential to be combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005
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- 2018
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14. Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by the Groupe Francophone Des Myélodysplasies
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Lionel Ades, Thomas Prebet, Aspasia Stamatoullas, Christian Recher, Romain Guieze, Emmanuel Raffoux, Krimo Bouabdallah, Mathilde Hunault, Eric Wattel, Laure Stalnikiewicz, Andrea Toma, Hervé Dombret, Norbert Vey, Marie Sebert, Claude Gardin, Cendrine Chaffaut, Sylvie Chevret, and Pierre Fenaux
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within a complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with intensive chemotherapy in a phase II study. Treatment consisted of daunorubicin (45 mg/m2/day, days 1–3 in cohort 1, escalated to 60 mg/m2/day, days 1–3 in cohorts 2 and 3) combined with cytosine arabinoside (200 mg/m2/day, days 1–7) and lenalidomide (10 mg/day, days 1–21 in cohorts 1 and 2, escalated to 25 mg/day, days 1–21 in cohort 3). Eighty-two patients with 5q deletion were enrolled, including 62 with acute myeloblastic leukemia, 62/79 (78%) of whom had a complex karyotype (median 7 cytogenetic abnormalities, all but 2 of them monosomal) and three had unknown karyotypes. Thirty-eight patients (46%) achieved complete remission and the overall response rate was 58.5%. Among the 62 patients with a complex karyotype, 27 achieved complete remission (44%) and 21 had cytogenetic responses. A lower response rate was observed in patients with acute myeloblastic leukemia but other pretreatment factors, including cytogenetic complexity and treatment cohort, did not significantly influence response. Fifteen patients underwent allogeneic stem cell transplantation, including 11 patients in first remission. The 1-year cumulative incidence of relapse was 64.6% and the median overall survival was 8.2 months. By comparison with conventional intensive chemotherapy, the treatment protocol we used appeared to produce higher hematologic and cytogenetic complete remission rates in patients with very poor cytogenetics, but response duration was short in this very poor risk population, highlighting the need for better post-induction strategies. Clinical trial registry number: NCT00885508
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- 2017
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15. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association
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Clémentine Sarkozy, Thierry Molina, Hervé Ghesquières, Anne-Sophie Michallet, Jehan Dupuis, Diane Damotte, Franck Morsschauser, Marie Parrens, Laurent Martin, Peggy Dartigues, Aspasia Stamatoullas, Pierre Hirsch, Bettina Fabiani, Krimo Bouabdallah, Maria Gomes da Silva, Marie Maerevoet, Camille Laurent, Bertrand Coiffier, Gilles Salles, and Alexandra Traverse-Glehen
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma). The median age was 32 years (13–83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalated BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.
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- 2017
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16. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.
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Mariane de Montalembert, Jean-Antoine Ribeil, Valentine Brousse, Agnes Guerci-Bresler, Aspasia Stamatoullas, Jean-Pierre Vannier, Cécile Dumesnil, Agnès Lahary, Mohamed Touati, Krimo Bouabdallah, Marina Cavazzana, Emmanuelle Chauzit, Amandine Baptiste, Thibaud Lefebvre, Hervé Puy, Caroline Elie, Zoubida Karim, Olivier Ernst, and Christian Rose
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Medicine ,Science - Abstract
The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P
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- 2017
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17. Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma
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Vincent Camus, Aspasia Stamatoullas, Sylvain Mareschal, Pierre-Julien Viailly, Nasrin Sarafan-Vasseur, Elodie Bohers, Sydney Dubois, Jean Michel Picquenot, Philippe Ruminy, Catherine Maingonnat, Philippe Bertrand, Marie Cornic, Valérie Tallon-Simon, Stéphanie Becker, Liana Veresezan, Thierry Frebourg, Pierre Vera, Christian Bastard, Hervé Tilly, and Fabrice Jardin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma, in biopsies and plasma circulating cell-free DNA from patients with classical Hodgkin lymphoma using a highly sensitive digital PCR technique. A total of 94 patients were included in the present study. This widely expressed XPO1 E571K mutation is present in one quarter of classical Hodgkin lymphoma patients (24.2%). Mutated and wild-type classical Hodgkin lymphomas were similar regarding the main clinical features. Patients with a detectable XPO1 mutation at the end of treatment displayed a tendency toward shorter progression-free survival, as compared to patients with undetectable mutation in plasma cell-free DNA (2-year progression-free survival: 57.1%, 95% confidence interval: 30.1–100% versus 2-year progression-free survival: 90.5%, 95% confidence interval: 78.8–100%, respectively, P=0.0601). To conclude, the detection of the XPO1 E571K mutation in biopsy and plasma cell-free DNA by digital PCR may be used as a novel biomarker in classical Hodgkin lymphoma for both diagnosis and minimal residual disease, and pinpoints a crucial role of XPO1 in classical Hodgkin lymphoma pathogenesis. The detection of somatic mutation in the plasma cell-free DNA of patients represents a major technological advance in the context of liquid biopsies and noninvasive management of classical Hodgkin lymphoma.
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- 2016
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18. A randomized phase II trial of azacitidine +/− epoetin-β in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents
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Sylvain Thépot, Raouf Ben Abdelali, Sylvie Chevret, Aline Renneville, Odile Beyne-Rauzy, Thomas Prébet, Sophie Park, Aspasia Stamatoullas, Agnes Guerci-Bresler, Stéphane Cheze, Gérard Tertian, Bachra Choufi, Laurence Legros, Jean Noel Bastié, Jacques Delaunay, Marie Pierre Chaury, Laurence Sanhes, Eric Wattel, Francois Dreyfus, Norbert Vey, Fatiha Chermat, Claude Preudhomme, Pierre Fenaux, and Claude Gardin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The efficacy of azacitidine in patients with anemia and with lower-risk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-β. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one “epigenetic mutation” and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352).
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- 2016
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19. Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program
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Aurore Perrot, Hélène Monjanel, Réda Bouabdallah, Philippe Quittet, Clémentine Sarkozy, Marc Bernard, Aspasia Stamatoullas, Cécile Borel, Krimo Bouabdallah, Emmanuelle Nicolas-Virelizier, Marion Fournier, Franck Morschhauser, and Pauline Brice
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Brentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of between 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 lines of chemotherapy, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed as decreased (39.3%) in the 28 patients >60 years. The median response duration was 8.4 months. With median follow-up at 16.1 months, median progression-free survival was 6.8 months and this was significantly longer for patients transplanted after brentuximab vedotin (a median of 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because of the short-term responses in most patients, a high-dose therapy with stem cell transplantation for responders should be considered as quickly as possible.
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- 2016
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20. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study
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Julien Lazarovici, Peggy Dartigues, Pauline Brice, Lucie Obéric, Isabelle Gaillard, Mathilde Hunault-Berger, Florence Broussais-Guillaumot, Emmanuel Gyan, Serge Bologna, Emmanuelle Nicolas-Virelizier, Mohamed Touati, Olivier Casasnovas, Richard Delarue, Frédérique Orsini-Piocelle, Aspasia Stamatoullas, Jean Gabarre, Luc-Matthieu Fornecker, Thomas Gastinne, Fréderic Peyrade, Virginie Roland, Emmanuel Bachy, Marc André, Nicolas Mounier, and Christophe Fermé
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.
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- 2015
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21. Classical Hodgkin’s lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant
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Eric Van Den Neste, Olivier Casasnovas, Marc André, Mohamed Touati, Delphine Senecal, Véronique Edeline, Aspasia Stamatoullas, Luc Fornecker, Bénédicte Deau, Thomas Gastinne, Oumédaly Reman, Isabelle Gaillard, Cécile Borel, Pauline Brice, and Christophe Fermé
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The Hodgkin’s Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin’s lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin’s lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including 18fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin’s lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.
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- 2013
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22. Daily practice management of myelodysplastic syndromes in France: data from 907 patients in a one-week cross-sectional study by the Groupe Francophone des Myélodysplasies
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Charikleia Kelaidi, Aspasia Stamatoullas, Odile Beyne-Rauzy, Emmanuel Raffoux, Bruno Quesnel, Agnes Guerci, François Dreyfus, Sabine Brechignac, Christian Berthou, Thomas Prebet, Yosr Hicheri, Maya Hacini, Jacques Delaunay, Marie-Pierre Gourin, Jean-Marie Camo, Hacene Zerazhi, Anne-Laure Taksin, Laurence Legros, Bachra Choufi, and Pierre Fenaux
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background There is little published information on the everyday clinical management of myelodysplastic syndromes in real world practice.Design and Methods We conducted a cross-sectional study of all patients with myelodysplastic syndromes attending 74 French centers in a 1-week period for inpatient admission, day-hospital care or outpatient visits.Results Nine hundred and seven patients were included; 67.3% had lower-risk myelodysplastic syndromes (International Prognostic Scoring System: low or intermediate-1). Karyotype had been analyzed in 82.5% of the cases and was more often of intermediate or poor risk in patients under 65 years old compared with those who were older. Red blood cell transfusions accounted for as many as 31.4% of the admissions. Endogenous erythropoietin level was less than 500 IU/L in 88% of the patients tested. Erythroid stimulating agents had been or were being used in 36.8% of the lower risk patients, iron chelation in 31% of lower risk patients requiring red blood cell transfusions and lenalidomide in 41% of lower risk patients with del 5q. High-dose chemotherapy, hypomethylating agents, low dose cytarabine and allogeneic stem cell transplantation had been or were being used in 14.8%, 31.1%, 8.8% and 5.1%, respectively, of higher-risk patients.Conclusions Karyotype is now assessed in most patients with myelodysplastic syndromes, and patients under 65 years old may have more aggressive disease. Apart from erythroid-stimulating agents and, in higher-risk myelodysplastic syndromes, hypomethylating agents, specific treatments are used in a minority of patients with myelodysplastic syndromes and red blood cell transfusions still represent the major reason for hospital admission.
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- 2010
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23. Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome unclassifiable – a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT
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Joanna Drozd-Sokolowska, Luuk Gras, Nienke Zinger, Mohsen Al Zahrani, Jakob Passweg, Jenny Byrne, Aloysius Ho, Xiao-jun Huang, Nicolaus Kröger, Jiri Mayer, Domenico Russo, Ann De Becker, Abdelghani Tbakhi, Aspasia Stamatoullas, Thomas Valerius, Patrick Hayden, Donal P. McLornan, Francesco Onida, Christof Scheid, Marie Robin, Ibrahim Yakoub-Agha, Hematology, and Faculty of Medicine and Pharmacy
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Transplantation ,myelodysplastic syndrome unclassifiable ,Hematology ,Allogeneic hematopoietic cell transplantation - Published
- 2023
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24. Work and education interruption in long-term Hodgkin lymphoma survivors : an analysis among patients from nine EORTC-LYSA trials
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Sidsel J. Juul, Sára Rossetti, Michal Kicinski, Marleen A. E. van der Kaaij, Francesco Giusti, Paul Meijnders, Berthe M. P. Aleman, John M. M. Raemaekers, Hanneke C. Kluin-Nelemans, Michele Spina, Christophe Fermé, Loïc Renaud, Olivier Casasnovas, Aspasia Stamatoullas, Marc André, Fabien Le Bras, Wouter J. Plattel, Michel Henry-Amar, Martin Hutchings, Maja V. Maraldo, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie
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education ,work ,Oncology ,employment ,Radiology, Nuclear Medicine and imaging ,Hematology ,General Medicine ,Human medicine ,survivorship ,Hodgkin lymphoma - Abstract
Background: Disease-specific studies on the impact of Hodgkin lymphoma (HL) on education or work interruption and resumption are lacking. Material and methods: In a cross-sectional study conducted among long-term HL survivors enrolled from 1964 to 2004 in nine randomised EORTC-LYSA trials, the interruption and resumption of education/work was investigated. Survivors alive 5-44 years after diagnosis who were studying or working at time of diagnosis were included (n = 1646). Patient and treatment characteristics were obtained from trial records. Education and work outcomes were collected using the Life Situation Questionnaire. Logistic regression was used to model education or work interruption; Cox regression was used to study resumption rates. Results: Among survivors studying at time of diagnosis (n = 323), 52% (95% CI: 46-57%) interrupted their education; however, it was resumed within 24 months by 92% (95% CI: 87-96%). The probability of interruption decreased with time: the more recent the treatment era, the lower the risk (OR 0.70 per 10 years, 95% CI: 0.49-1.01). Treatment with radiotherapy (yes vs. no) was associated with a higher education resumption rate (HR 2.01, 95% CI 1.07-3.78) whereas age, sex, stage, radiotherapy field and chemotherapy were not.Among survivors working at time of diagnosis (n = 1323), 77% (95% CI: 75-79%) interrupted their work. However, it was resumed within 24 months by 86% (95% CI: 84%-88%). Women were more likely to interrupt their work as compared to men (OR 1.90, 95% CI: 1.44-2.51) and, when interrupted, less likely to resume work (HR 0.70, 95% CI: 0.61-0.80). Survivors with a higher educational level were less likely to interrupt their work (OR 0.68 for university vs. no high school, 95% CI: 0.46-1.03); and when interrupted, more likely to resume work (HR 1.50 for university vs. no high school, 95% CI: 1.21-1.86). Increasing age was also associated with lower resumption rates (HR 0.62 for age ≥50 vs. 18-29 years, 95% CI: 0.41-0.94). Conclusion: An interruption in education/work was common among long-term HL survivors. However, most of the survivors who interrupted their studies or work had resumed their activities within 24 months. In this study, no associations between survivors' characteristics and failure to resume education were observed. Female sex, age ≥50 years, and a lower level of education were found to be associated with not resuming work after treatment for HL.
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- 2023
25. Prognostic value of baseline metabolic tumour volume in advanced-stage Hodgkin’s lymphoma
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Stéphanie Becker, Pierre Vera, Pierre Pinochet, Edgar Texte, Aspasia Stamatoullas-Bastard, and Sorina-Dana Mihailescu
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Adult ,Male ,Oncology ,BEACOPP ,medicine.medical_specialty ,medicine.medical_treatment ,Science ,Population ,Article ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Stage (cooking) ,education ,Survival analysis ,Retrospective Studies ,education.field_of_study ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Hodgkin's lymphoma ,Hodgkin Disease ,Progression-Free Survival ,Tumor Burden ,Lymphoma ,ABVD ,Positron emission tomography ,Positron-Emission Tomography ,Medicine ,Female ,business ,Hodgkin lymphoma ,medicine.drug - Abstract
Our aim was to evaluate the prognostic value of initial total metabolic tumour volume (TMTV) in a population of patients with advanced-stage Hodgkin’s lymphoma (HL). We retrospectively included 179 patients with stage IIb-III-IV Hodgkin’s disease who received BEACOPP or ABVD as the first-line treatment. The initial TMTV was determined using a semi-automatic method for each patient. We analysed its prognostic value in terms of 5-year progression-free survival (PFS), overall survival, and positron emission tomography (PET) response after two courses of chemotherapy. Considering all the treatments and using a threshold of 217 cm3, TMTV was predictive of 5-year PFS and PET response after two courses of chemotherapy. In multivariable analysis involving TMTV, IPI score, and the first treatment received, TMTV remained a baseline prognostic factor for 5-year PFS. In the subgroup of patients treated with BEACOPP with a threshold of 331 cm3, TMTV was predictive of PET response, but not 5-year PFS (p = 0.087). The combined analysis of TMTV and PET response enabled the individualisation of a subgroup of patients (low TMTV and complete response on PET) with a very low risk of recurrence. Baseline TMTV appears to be a useful independent prognostic factor for predicting relapse in advanced-stage HL in ABVD subgroup, with a tendency of survival curves separation in BEACOPP subgroup.
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- 2021
26. Prognostic relevance of sarcopenia, geriatric, and nutritional assessments in older patients with diffuse large B-cell lymphoma: results of a multicentric prospective cohort study.
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Juliette, Pénichoux, Hélène, Lanic, Caroline, Thill, Anne-Lise, Ménard, Vincent, Camus, Aspasia, Stamatoullas, Emilie, Lemasle, Stéphane, Leprêtre, Pascal, Lenain, Nathalie, Contentin, Jerôme, Kraut-Tauzia, Christophe, Fruchart, Leila, Kammoun, Gandhi, Damaj, Agathe, Farge, Caroline, Delette, Romain, Modzelewski, Sandrine, Vaudaux, Louis-Ferdinand, Pépin, and Hervé, Tilly
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OLDER patients ,NUTRITIONAL assessment ,DIFFUSE large B-cell lymphomas ,SARCOPENIA ,ACTIVITIES of daily living ,COHORT analysis - Abstract
This prospective study aimed to investigate the prognostic effect of sarcopenia, geriatric, and nutritional status in older patients with diffuse large B-cell lymphoma (DLBCL). Ninety-five patients with DLBCL older than 70 years who were treated with immunochemotherapy were included. The lumbar L3 skeletal muscle index (L3-SMI) was measured by computed tomography at baseline, and sarcopenia was defined as low L3-SMI. Geriatric assessment included G8 score, CIRS-G scale, Timed Up and Go test, and instrumental activity of daily living. Nutritional status was assessed using the Mini Nutritional Assessment and the body mass index, and several scores used in the literature incorporating nutritional and inflammatory biomarkers, namely the Nutritional and inflammatory status (NIS), Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Glasgow Prognostic Score. Fifty-three patients were considered sarcopenic. Sarcopenic patients displayed higher levels of inflammation markers and lower levels of prealbumin than non-sarcopenic patients. Sarcopenia was associated with NIS, but was not associated with severe adverse events and treatment disruptions. They were, however, more frequent among patients with elevated NIS. Sarcopenia did not appear in this study as a prognostic factor for progression-free survival (PFS) or overall survival (OS). However, NIS emerged as predictive of the outcome with a 2-year PFS rate of 88% in the NIS ≤ 1 group and 49% in the NIS > 1 group and a significant effect in a multivariate analysis for both PFS (p = 0.049) and OS (HR = 9.61, CI 95% = [1.03–89.66], p = 0.04). Sarcopenia was not associated with adverse outcomes, but was related to NIS, which appeared to be an independent prognostic factor. [ABSTRACT FROM AUTHOR]
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- 2023
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27. A phase II study of guadecitabine in higher-risk myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure
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Sophie Park, Anne Banos, Cendrine Chaffaut, Cecile Bally, Kamel Laribi, Laurence Legros, Aline Renneville, Pierre Fenaux, Emmanuel Gyan, Eric Wattel, Marie Sebert, Marie-Pierre Gourin, Sylvie Chevret, Claude Preudhomme, Simone Jueliger, Fatiha Chermat, Pierre Peterlin, Olivier Nibourel, Odile Beyne-Rauzy, Lionel Ades, Rosa Sapena, Aspasia Stamatoullas, Luke Bevan, and Laurence Sanhes
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Male ,Risk ,medicine.medical_specialty ,Azacitidine ,Decitabine ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,medicine ,Humans ,Survival analysis ,Aged ,business.industry ,Myeloid leukemia ,Hematology ,medicine.disease ,Survival Analysis ,Leukemia ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Hypomethylating agent ,International Prognostic Scoring System ,Myelodysplastic Syndromes ,Female ,business ,030215 immunology ,medicine.drug - Abstract
High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years [Interquartile Range (IQR) 69-76]. Fifty-five patients received at least one cycle of guadecitabine (60 mg/m2/d subcutaneously days 1-5 per 28-day treatment cycles), with a median of 3 cycles (range, 0-27). Eight (14.3%) patients responded, including two complete responses; median response duration was 11.5 months. Having no or few identified somatic mutations was the only factor predicting response (P=0.035). None of the 11 patients with TP53 mutation responded. Median overall survival was 7.1 months, and 17.9 months in responders (3 of whom had overall survival >2 years). In multivariate analysis, IPSS-R (revised International Prognostic Scoring System) score other than very high (P=0.03) primary versus secondary azacitidine failure (P=0.01) and a high rate of demethylation in blood during the first cycle of treatment (P=0.03) were associated with longer survival. Thus, guadecitabine can be effective, sometimes yielding relatively prolonged survival, in a small proportion of high-risk myelodysplastic syndrome/low blast count acute myeloid leukemia patients who failed azacitidine. (Trial registered at clinicaltrials.gov identifier: 02197676).
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- 2019
28. Relapsed and refractory classical Hodgkin lymphoma: could virotherapy help solve the equation?
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Julien Lazarovici, Clémentine Sarkozy, Vincent Ribrag, Stéphane Champiat, Aspasia Stamatoullas, Jean-Marie Michot, Fabrice Jardin, Aurélien Marabelle, and Selma Addou
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Oncology ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,medicine.medical_treatment ,030231 tropical medicine ,Immunology ,Review ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Classical Hodgkin lymphoma ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Virotherapy ,Pharmacology ,Oncolytic Virotherapy ,Chemotherapy ,business.industry ,Epstein–Barr virus ,Hodgkin Disease ,Oncolytic virus ,Radiation therapy ,Oncolytic Viruses ,Hodgkin lymphoma ,business - Abstract
Classical Hodgkin lymphoma is a neoplastic hematological disease. Standard first-line therapy, including chemotherapy and radiotherapy, is curative in >85% of early-stage patients, with a 5-year survival rate of >95%. However, approximately 15% of patients have hard-to-treat lymphoma with poor outcomes, and new treatment strategies are needed for these young adults. There are several well-documented cases in the medical literature on hematologic cancer remission following natural human viral infections. Therefore, hoping to reproduce these spontaneous tumor regressions, researchers have been investigating various viruses with oncolytic properties. There is a high rationale for using virotherapy in the treatment of Hodgkin lymphoma, in which tumor cells are often infected with the Epstein-Barr virus. Modern viral technologies and current knowledge about the relationship between viruses and cancer could accelerate the discovery of effective viral oncolytic therapies. This article reviews the use of oncolytic viruses as innovative therapies for treating Hodgkin lymphoma.
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- 2021
29. SUV max -based assessment of PET response shows a superior specificity to Deauville criteria for predicting recurrence in Hodgkin’s lymphoma
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Stéphanie Becker, Edgar Texte, Aspasia Stamatoullas, Hervé Tilly, J. Lequesne, Fabrice Jardin, Pierre Vera, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), and Normandie Université (NU)
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Oncology ,Cancer Research ,medicine.medical_specialty ,Optimal cutoff ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Hodgkin’s Lymphoma ,Deauville score ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,tumor/liver ratio ,18fdg pet ,deltaSUVmax ,High rate ,Chemotherapy ,business.industry ,Hematology ,Therapeutic evaluation ,Hodgkin's lymphoma ,medicine.disease ,3. Good health ,Lymphoma ,PET ,030220 oncology & carcinogenesis ,Cohort ,business ,030215 immunology - Abstract
International audience; One of the limitations of 18FDG PET/CT for therapeutic evaluation in Hodgkin's Lymphoma is the relatively high rate of false positive uptake. SUVmax reduction (ΔSUVmax) and tumor/liver ratio (TLr) are promising tools for response assessment in lymphoma. We determined the optimal cutoff values for ΔSUVmax and TLr and compared them to Deauville score (DS) after two and four cycles chemotherapy (PET2 and PET4 respectively) and at the end of treatment PET (PETeot) on a cohort of 362 patients. TLr showed better diagnostic performances than DS for predicting 5-year progression-free survival (PFS), especially on early PET/CT assessments. Positive predictive values at PET2 for TLr, ΔSUVmax and DS were 51%, 34% and 31% respectively. On the multivariable analysis, significant predictive factors of PFS were TLr (at PET2, PET4 and PETeot) and ΔSUVmax (at PET4 and PETeot). DS was not significantly associated with PFS at any PET timing.
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- 2021
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30. Vasculitis associated with myelodysplastic syndrome and chronic myelomonocytic leukemia: French multicenter case-control study
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Jean-Sébastien Allain, Laure Swiader, Pierre Peterlin, Emmanuel Dao, Carole Philipponnet, Pierre Fenaux, Alexis Régent, Sylvain Thepot, Eric Solary, Philippe Guilpain, Benjamin Terrier, Noemie Jourde Chiche, Rolande Cohen-Valensi, Ygal Benhamou, On behalf Minhemon, Anne Laure Roupie, Jonathan Broner, Amadou Konate, Matthieu Wemeau, Guillaume Bussone, Matthieu Ponsoye, J. Galland, Aline Tanguy-Schmidt, Marielle Roux-Sauvat, Guilhem Cavaille, Xavier Puéchal, Olivier Fain, Azeddine Dellal, Nadia Baati, Hubert de Boysson, Maud D'Aveni, Vincent Jachiet, Aspasia Stamatoullas-Bastard, Constance Lahuna, Lionel Ades, Lenaig Le Clech, Arsène Mekinian, Alexis Guédon, Marc Lambert, Achille Aouba, Anne Parcelier, Sélim Corm, J. Seguier, Snfmi., Mathilde Versini, Emmanuel Ledoult, Matthieu Groh, Marc Ruivard, Fabrice Carrat, Benoit de Renzis, Julien Rossignol, Lise Willems, François Maurier, Anne Marfaing Koka, Nicolas Schleinitz, Viviane Queyrel, Cristina Belizna, Valérie Noc, Andrei Tchirkov, Louis Terriou, Grégoire Martin de Frémont, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
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Adult ,Male ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Giant Cell Arteritis ,Chronic myelomonocytic leukemia ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Rheumatology ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,ComputingMilieux_MISCELLANEOUS ,Aged ,Retrospective Studies ,030203 arthritis & rheumatology ,Aged, 80 and over ,Acute leukemia ,business.industry ,Polyarteritis nodosa ,Case-control study ,Leukemia, Myelomonocytic, Chronic ,Odds ratio ,Middle Aged ,medicine.disease ,3. Good health ,Giant cell arteritis ,Anesthesiology and Pain Medicine ,International Prognostic Scoring System ,Case-Control Studies ,Myelodysplastic Syndromes ,Female ,business ,Vasculitis - Abstract
Introduction Our objective was to evaluate characteristics, treatment and outcome of vasculitis associated with myelodysplastic syndrome (MDS) and chronic myelomonicytic leukemia (CMML) Patients and Methods Retrospective descriptive analysis of MDS/CMML-related vasculitis and comparison with MDS/CMML patients without dysimmune features. Results Seventy patients with vasculitis and MDS/CMML were included, with median age of 71.5 [21–90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/CMML in 31 patients (44%), and after in 20 patients. In comparison with MDS/CMML without autoimmune/inflammatory features, vasculitis with MDS/MPN showed no difference in MDS/CMML subtypes distribution nor International Prognostic Scoring System and CMML-specific prognostic (IPSS/CPSS) scores. Vasculitis subtypes included Giant cell arteritis in 24 patients (34%), Behcet's-like syndrome in 11 patients (20%) and polyarteritis nodosa in 6 patients (9%). Glucocorticoids (GCs) were used as first-line therapy for MDS/CMML vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After a median follow-up of 33.2 months [1–162], 31 patients (44%) achieved sustained remission. At least one relapse occurred in 43 patients (61%). Relapse rates were higher in patients treated with conventional Disease Modifying Anti-Rheumatic Drug (DMARDs) (odds ratio 4.86 [95% CI 1.38 - 17.10]), but did not differ for biologics (odds ratio 0.59 [95% CI 0.11–3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21–9.76]) than under glucocorticoids. Overall survival in MDS/CMML vasculitis was not significantly different from MDS/CMML patients without autoimmune/inflammatory features (p = 0.5), but acute leukemia progression rates were decreased (log rank Conclusion This study shows no correlation of vasculitis diagnoses with subtypes and severity of MDS/CMML, and no significant impact of vasculitis on overall survival. Whereas conventional DMARDs seem to be less effective, biologics or azacytidine therapy could be considered for even low-risk MDS/CMML vasculitis.
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- 2020
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31. Patient and physician preferences for first‐line treatment of classical Hodgkin lymphoma in Germany, France and the United Kingdom
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Paul J Bröckelmann, Mehul Dalal, Timothy M Illidge, Dirk Huebner, Kerstin Mueller, Suzanne McMullen, Ashish Gautam, Erin Zagadailov, J Ben Wilson, Aspasia Stamatoullas, and Sarah Goring
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Oncology ,BEACOPP ,Male ,medicine.medical_treatment ,Procarbazine ,0302 clinical medicine ,Prednisone ,Germany ,Antineoplastic Combined Chemotherapy Protocols ,Practice Patterns, Physicians' ,Brentuximab vedotin ,Manchester Cancer Research Centre ,Haematological Malignancy ,Patient Preference ,Hematology ,Middle Aged ,Hodgkin Disease ,Vinblastine ,Survival Rate ,Vincristine ,030220 oncology & carcinogenesis ,Female ,France ,medicine.drug ,Research Paper ,Adult ,medicine.medical_specialty ,Dacarbazine ,Disease-Free Survival ,03 medical and health sciences ,patient and physician preferences ,Bleomycin ,Internal medicine ,medicine ,Humans ,Adverse effect ,Cyclophosphamide ,Aged ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,discrete choice experiment ,ABVD ,United Kingdom ,Cross-Sectional Studies ,Doxorubicin ,business ,Hodgkin lymphoma ,030215 immunology - Abstract
Summary First‐line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPP escalated (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography‐driven strategies and ABVD or BEACOPP variants incorporating the antibody‐drug conjugate brentuximab vedotin (BV) or anti‐PD1 antibodies are under investigation in advanced‐stage patients. The present study aimed to elicit preferences for attributes associated with ABVD, BEACOPP escalated and BV‐AVD (BV, adriamycin, vinblastine and dacarbazine) among patients and physicians. Cross‐sectional online discrete choice experiments were administered to HL patients (n = 381) and haematologists/oncologists (n = 357) in France, Germany and the United Kingdom. Included attributes were progression‐free survival (PFS), overall survival (OS), and the risk of neuropathy, lung damage, infertility and hospitalisation due to adverse events. Whereas 5‐year PFS and OS were the most important treatment attributes to patients, the relative importance of each attribute and preference weights for each level varied among physicians according to the description of the hypothetical patient for whom treatment was recommended. PFS and OS most strongly influenced physicians’ recommendations when considering young female patients who did not want children or young male patients. Infertility was more important to physicians’ treatment decision than PFS when considering young women with unknown fertility preferences, whereas hospitalisations due to adverse events played the largest role in treatment decisions for older patients.
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- 2018
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32. Non-invasive monitoring of diffuse large B-cell lymphoma by cell-free DNA high-throughput targeted sequencing: analysis of a prospective cohort
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Hélène Lanic, Pierre-Julien Viailly, Philippe Bertrand, Philippe Ruminy, Stéphanie Becker, Louis-Ferdinand Pepin, Vincent Camus, Emilie Lemasle, Julie Libraire, Elodie Bohers, Stéphane Leprêtre, Vinciane Marchand, Sandrine Vaudaux, Catherine Maingonnat, Pascaline Etancelin, Pascal Lenain, Jean-Michel Picquenot, Anne-Lise Menard, Fabrice Jardin, Pierre Vera, Aspasia Stamatoullas, Nathalie Contentin, Hervé Tilly, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-CRLCC Henri Becquerel, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'Hématologie, CRLCC Henri Becquerel, Service d'hématologie, Unité de recherche clinique, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Unité de recherche clinique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), This research was supported by grants from the Cancéropole Nord-Ouest, the Ligue Contre le Cancer, and Henri Becquerel Center., and Breton, Céline
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Male ,0301 basic medicine ,Oncology ,0302 clinical medicine ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,Prospective cohort study ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,medicine.diagnostic_test ,High-Throughput Nucleotide Sequencing ,DNA, Neoplasm ,Hematology ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell-free fetal DNA ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,Cell-Free Nucleic Acids ,Adult ,medicine.medical_specialty ,DNA Copy Number Variations ,Genotype ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Context (language use) ,lcsh:RC254-282 ,Article ,Young Adult ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,Biopsy ,Biomarkers, Tumor ,medicine ,Humans ,Clinical significance ,Liquid biopsy ,Alleles ,Aged ,business.industry ,Liquid Biopsy ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,medicine.disease ,Lymphoma ,030104 developmental biology ,business ,Diffuse large B-cell lymphoma - Abstract
From a liquid biopsy, cell-free DNA (cfDNA) can provide information regarding basal tumoral genetic patterns and changes upon treatment. In a prospective cohort of 30 diffuse large B-cell lymphomas (DLBCL), we determined the clinical relevance of cfDNA using targeted next-generation sequencing and its correlation with PET scan imaging at the time of diagnosis and during treatment. Using a dedicated DLBCL panel, mutations were identified at baseline for 19 cfDNAs and profiles were consistent with expected DLBCL patterns. Tumor burden-related clinical and PET scan features (LDH, IPI, and metabolic tumor volume) were significantly correlated with the quantity of tumoral cfDNA. Among the four patients presenting additional mutations in their cfDNAs, three had high metabolic tumor volumes, suggesting that cfDNA more accurately reflects tumor heterogeneity than tissues biopsy itself. Mid-treatment, four patients still had basal mutations in their cfDNAs, including three in partial response according to their Deauville scores. Our study highlights the major interests in liquid biopsy, in particular in the context of bulky tumors where cfDNA allows capturing the entire tumoral mutation profile. Therefore, cfDNA analysis in DLBCL represents a complementary approach to PET scan imaging.
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- 2018
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33. Outcome of Patients with Hodgkin Lymphoma Treated with Brentuximab Vedotin for Relapse after Autologous Stem Cell Transplant: A Retrospective Analysis of the LWP-EBMT
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Matthew Collin, Zübeyde Nur Özkurt, Pauline Brice, Herve Ghesquieres, Luca Castagna, Ariane Boumendil, Andrei Colita, Björn E. Wahlin, Didier Blaise, Radovan Vrhovac, Irma Khvedelidze, Maurizio Musso, Rocco Pastano, Silvia Montoto, M S Rauf, Tadeusz Robak, Ali Bazarbachi, Eleonora Alma, Nikesh Dhiraj Chavda, Stephen D. Robinson, Saad Akhtar, Joanna Romejko-Jarosinska, Keith Wilson, Herve Finel, Aspasia Stamatoullas, Mutlu Arat, and Nadira Duraković
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Melphalan ,Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Transplantation ,Graft-versus-host disease ,Internal medicine ,Cytarabine ,medicine ,Stem cell ,business ,Brentuximab vedotin ,Etoposide ,medicine.drug - Abstract
Around half of patients with Hodgkin Lymphoma (HL) who progress or relapse through first line therapy can be cured with salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, this leaves approximately 50% of patients that will relapse after ASCT. The pivotal phase II SG035-00303 trial demonstrated that these patients can be successfully treated with Brentuximab Vedotin (BV), and a proportion of them can be long term free of disease without any further intervention. The objective of the current study was to investigate whether these findings were borne out in the real world via interrogation of the EBMT registry. We retrospectively analysed data for 101 patients with HL who had BV as their first treatment for relapse after ASCT from 2012 to 2019. The median age at ASCT was 34 years (range: 19-65), 60% being male and with 62% being in complete response (CR) at the time of ASCT. Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) was the most common conditioning regimen, having been employed in 72% of the cases. The median time from ASCT to relapse was 10.1 months (interquartile range (IQR): 6.1-25.1). The median time on BV was 3.4 months (IQR: 2.1-5.24). BV treatment resulted in a best overall response rate (ORR) of 59% with a CR rate of 37%. At last follow-up only 2 patients remain on treatment with BV. The main reason for discontinuation of BV was progression which occurred in 37% of the patients. In 32 cases (33%) the treatment was stopped electively to proceed to a second transplant, and overall nearly a quarter (22%) completed the full treatment course. Only 5% of patients stopped due to toxicity (peripheral neuropathy 2 and neutropenia, infusion reaction and other, 1 each). Further therapy was given after BV in over half of evaluable patients (58%), with check point inhibitors (CPIs) being the most common agents used (24% of these). Nearly two thirds (64/101) of the patients received a second transplant, which were nearly all allogeneic stem cell transplant (alloSCT, 59/64), and most of these (49/59) with reduced intensity conditioning (RIC). 26% of the alloSCT recipients experienced grade II-IV acute graft versus host disease (GvHD) and 25% developed chronic GvHD. At last follow up, 62% of all patients were alive with a median follow-up of 25 months after starting BV. Of these, 27 had received a second transplant, who were mostly in CR at last follow up (26/27) and a further 22 had relapsed. There were 11 patients of the 63 still alive who continued to be responding to BV without further therapy with a median duration of response of 30 months. In conclusion BV use for relapse after ASCT was well tolerated generally, with only a minority of patients stopping treatment due to toxicity. However, although almost two thirds of the patients achieved a response, further treatment was often needed after BV, notably with CPIs and most patients were consolidated with a RIC alloSCT. These results confirm that only a minority of patients can achieve a durable remission with BV alone. Disclosures Brice: Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Blaise:Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria. Stamatoullas:Celgene: Honoraria; Takeda: Consultancy. Robak:Takeda: Consultancy, Research Funding; UCB: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grant, Research Funding; Amgen: Consultancy, Other: Travel grant; Roche: Consultancy, Other: Travel grant, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grant, Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Acerta: Research Funding; Morphosys AG: Research Funding. Wahlin:Roche and Gilead: Consultancy.
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- 2019
34. Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation
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Diane Damotte, Remy Dulery, Olivier Casasnovas, Caroline Regny, Lysa, Guillaume Manson, Adrien Chauchet, Georges Garnier, Emmanuelle Nicolas-Virelizier, Aspasia Stamatoullas, Jean-Marc Schiano, Krimo Bouabdallah, Hervé Ghesquières, Charles Herbaux, Jean-Baptiste Mear, Roch Houot, Marie-Pierre Moles-Moreau, Pauline Brice, Adrian Tempescul, Alain Delmer, Bénédicte Deau, Anna Schmitt, Laurent Dercle, Cécile Borel, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Princesse Grace [Monaco], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département Hématologie (FNCLCC), Centre Léon Bérard [Lyon], CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d’Hématologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Columbia University Medical Center (CUMC), Columbia University [New York], Hopital Saint-Louis [AP-HP] (AP-HP), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Bristol-Myers SquibbBristol-Myers Squibb, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CCSD, Accord Elsevier, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Time Factors ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Programmed Cell Death 1 Receptor ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Risk Factors ,Anti pd1 ,ComputingMilieux_MISCELLANEOUS ,Allogenic haematopoietic stem cell transplantation ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Hodgkin Disease ,Progression-Free Survival ,3. Good health ,[SDV] Life Sciences [q-bio] ,Haematopoiesis ,Nivolumab ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,France ,Immunotherapy ,Stem cell ,Checkpoint inhibitors ,Adult ,medicine.medical_specialty ,Adolescent ,Risk Assessment ,03 medical and health sciences ,Young Adult ,Refractory ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Aged ,Retrospective Studies ,Anti-PD1 ,business.industry ,Transplantation ,030104 developmental biology ,Hodgkin lymphoma ,business - Abstract
Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL).We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT.After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT.Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy.
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- 2019
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35. TARGETED GENOTYPING OF CIRCULATING TUMOR DNA FOR CLASSICAL HODGKIN LYMPHOMA MONITORING: A PROSPECTIVE STUDY
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Vincent Camus, Hélène Lanic, Emilie Lemasle, Fabrice Jardin, Jean-Michel Picquenot, Hervé Tilly, Pascaline Etancelin, Elodie Bohers, Stéphanie Becker, Aspasia Stamatoullas, B. Marcq, Mathieu Viennot, L. Burel, Stéphane Leprêtre, Anne-Lise Menard, Pascal Lenain, Marie Cornic, L. Bessi, Nathalie Contentin, Pierre-Julien Viailly, J. Loret, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)
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0303 health sciences ,Cancer Research ,business.industry ,[SDV]Life Sciences [q-bio] ,Hematology ,General Medicine ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Circulating tumor DNA ,030220 oncology & carcinogenesis ,Cancer research ,Classical Hodgkin lymphoma ,Medicine ,business ,Prospective cohort study ,Genotyping ,030304 developmental biology - Abstract
International audience; About Related Information ePDFPDF Request permission Export citation Add to favorites Track citationShare a linkShare on Email Facebook Twitter LinkedIn RedditIntroduction: The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed.Methods: We developed a targeted Next‐Generation sequencing (NGS) panel for fast analysis (AmpliSeq® technology) of nine commonly mutated genes in biopsy and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). A dedicated bioinformatics pipeline to optimize detections of variants with low rates and minimize artefactual misinterpretations was built. Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD‐like [73.5%] and other regimens [5.2%, for elderly patients] were included in this non‐interventional study (NCT02815137).Results: Median age of the patients was 33.5 years (range 20‐86) with a predominance of male patients, scleronodular subtype and ECOG 0‐1 (53.3%, 70% and 88.3%, respectively). Variants were identified in 33 (55%) patients, precisely in 16/30 (53.3%) and 30/60 (50%) of available biopsy and ctDNA samples respectively. Concordance between genetic profiles of biopsy and ctDNA was accurate for 22/30 patients (73.3%). Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1were found in 11.7% (mean number of variants by sample [range]: 1 [0‐1]), 25% (1.1 [0‐2]), 21.7% (1.4 [0‐2]), 1.7% (1 [0‐1]), 25% (1.3 [0‐3]), 6.7% (1 [0‐1]), 15% (1.4 [0‐3]), 5% (1.3 [0‐2]) and 31.7% (1.8 [0‐7]) of all patients, respectively. Unsupervised hierarchical clustering was performed among the 9 genes to represent the association of alterations (See Figure 1).Higher level of [ctDNA] at diagnosis was associated with adverse characteristics: age ≥45 years, presence of anemia (hemoglobin
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36. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study
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Richard Delarue, Emmanuelle Nicolas-Virelizier, Reda Bouabdallah, Veronique Edeline, Bertrand Joly, Adrian Tempescul, Hassan Farhat, Luc-Matthieu Fornecker, Peggy Dartigues, René-Olivier Casasnovas, Laurent Martin, Franck Morschhauser, Aspasia Stamatoullas, Pauline Brice, Marc André, Alain Delmer, Michel Meignan, Nicolas Mounier, Hervé Ghesquières, Jehan Dupuis, Philippe Quittet, Krimo Bouabdallah, Julien Lazarovici, Alina Berriolo-Riedinger, Anne-Claire Gac, Alexandra Traverse-Glehen, Pierre Feugier, Thierry Lamy, Thomas Gastinne, Hervé Maisonneuve, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Henri Mondor, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Sud Francilien, CHU Bordeaux [Bordeaux], Centre Léon Bérard [Lyon], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Département de biologie et pathologie médicales [Gustave Roussy], Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Nice (CHU Nice), LYSA Imaging (Créteil) (LYSA-IM), CHU Henri Mondor, CHU Dijon, Département d'Hematologie, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CRLCC Henri Becquerel, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie [Nantes], Hôpital Sud-Fancilien, CH Sud-Fancilien, Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie Hôpital Mignot, Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CH La Roche-sur-Yon, Service d’Hématologie Clinique [CHU Pontchaillou, Rennes], Service d'hématologie et immunologie pédiatrique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dinant-Godinne UCL Namur, Service de cancérologie, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [Créteil], Université Grenoble Alpes (UGA), Département Hématologie (FNCLCC), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe Régional d'Etudes sur le CANcer (GRECAN), IFR146-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse )-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département d'Hématologie Clinique [CHU Nantes], Université Mohamed Boudiaf de M'sila, Service d’Hématologie Clinique [CHRU Nancy], Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut d'Electronique et de Télécommunications de Rennes (IETR), Université de Nantes (UN)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre hospitalier La Roche-Sur-Yon, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologie morphologique, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Pathologie [CHU de Dijon], Service de Médecine Interne Clermont Ferrand (MéDECINE INTERNE - CLERMONT-FERRAND), Hopital, Hôpital Archet 2 [Nice] (CHU), Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, CH Evry-Corbeil, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CCSD, Accord Elsevier, Service d'Hématologie Clinique (CHU de Dijon), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d’Hématologie [Rouen], CHU Rouen, Service hématologie Créteil, CHU, Laboratoire d'Hématologie Biologique [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Département de médecine nucléaire (Institut Curie, Saint-Cloud), Institut Curie [Paris], Hématologie clinique [CH La Roche-sur-Yon], service hématologie Strasbourg, CHU Strasbourg, Service d’Hématologie Clinique [Rennes], Service hématologie Nice, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, CHU Henri Mondor [Créteil], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
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Adult ,Male ,medicine.medical_specialty ,Vincristine ,Dacarbazine ,[SDV]Life Sciences [q-bio] ,Salvage therapy ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Procarbazine ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,ComputingMilieux_MISCELLANEOUS ,Neoplasm Staging ,business.industry ,Standard treatment ,medicine.disease ,Hodgkin Disease ,3. Good health ,Vinblastine ,Drug Therapy, Computer-Assisted ,[SDV] Life Sciences [q-bio] ,Oncology ,ABVD ,030220 oncology & carcinogenesis ,Positron-Emission Tomography ,Female ,business ,Febrile neutropenia ,030215 immunology ,medicine.drug - Abstract
International audience; Background: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.Methods: AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated). BEACOPPescalated consisted of bleomycin 10 mg/m2 and vincristine 1·4 mg/m2 intravenously on day 8, etoposide 200 mg/m2 intravenously on days 1-3, doxorubicin 35 mg/m2 and cyclophosphamide 1250 mg/m2 intravenously on day 1, 100 mg/m2 oral procarbazine on days 1-7, and 40 mg/m2 oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2, bleomycin 10 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.Findings: From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (
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- 2019
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37. Superiority of Allogenic Stem Cell Transplantation after Anti-PD1 Therapy over Anti-PD1 Monotherapy Alone in Relapse/Refractory Hodgkin Lymphoma Real World Evidence from the French Early Access Program
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Emmanuelle Nicolas-Virelizier, Remy Dulery, Adrien Chauchet, Roch Houot, Jean Marc Schiano de Collela, Herv Ghesquieres, Guillaume Manson, Anna Schmitt, Alain Delmer, Aspasia Stamatoullas, Jean-Baptiste Mear, Cécile Borel, Charles Herbaux, Georges Garnier, Rene-Olivier Casasnovas, Marie-Pierre Moles, Krimo Bouabdallah, Adrian Tempescul, Pauline Brice, Laurent Dercle, Lysiane Molina, Bénédicte Deau-Fisher, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CRLCC Centre Paoli - Calmettes [Marseille], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Princesse Grace [Monaco], CHU Grenoble, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hopital Saint-Louis [AP-HP] (AP-HP), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Cell Biology ,Hematology ,Real world evidence ,Biochemistry ,3. Good health ,Transplantation ,03 medical and health sciences ,030104 developmental biology ,Internal medicine ,medicine ,Refractory Hodgkin Lymphoma ,Stem cell ,Anti pd1 ,business ,ComputingMilieux_MISCELLANEOUS - Abstract
Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Figure 1). At the time of transplantation, 8 patients were in CR, 5 in partial response (PR) and 4 had progressed of whom 3 received a salvage therapy before alloHSCT. Interestingly, 6 out of 7 patients who were not in CR at the time of transplantation (5 PR and 1 progressive disease) converted into a CR after alloHSCT. At the time of analysis, 14 patients were alive and 13 remained disease-free after a median follow-up of 30.4 months. One-year OS and PFS from alloHSCT were 82% and 76%, respectively. Among responding patients (i.e. in CR or PR) after nivolumab monotherapy, those who underwent subsequent alloHSCT (N=13) had a better outcome than those who were not consolidated with alloHSCT (N=35) (Figure 2). In the transplanted group, none of the patients relapsed whereas in the non-transplanted group 60% of the patients relapsed (p Conclusions: Although patients who achieve a CR upon anti-PD1 therapy may experience prolonged remissions, most R/R HL patients treated with anti-PD1 antibody eventually progress or relapse. Our study demonstrates unprecedented disease-free survival in patients undergoing consolidation with alloHSCT after anti-PD1 therapy. Interestingly, alloHSCT post anti-PD1 can convert incomplete responses into CR in most cases. Despite expected toxicities, alloHSCT after anti-PD1 therapy appears manageable and safe in most patients. Our results suggest that consolidation with alloHSCT may represent a good option in patients treated with anti-PD1, notably in patients who are unable to achieve a CR. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Stamatoullas:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Consultancy. Brice:bristol myers squibb: Consultancy, Honoraria. Houot:bristol myers squibb: Consultancy, Honoraria.
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- 2018
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38. Efficacy of chemotherapy or chemo-anti-PD-1 combination after failed anti-PD-1 therapy for relapsed and refractory hodgkin lymphoma: A series from lysa centers
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Cécile Borel, Bénédicte Deau, Alexandra Traverse-Glehen, Pauline Brice, Thomas Filleron, Julien Lazarovici, Charles Herbaux, Salim Kanoun, Julia Gilhodes, Camille Golfier, Cédric Rossi, Sylvain Garciaz, Loic Ysebaert, Adrien Chauchet, Jehan Dupuis, Hervé Ghesquières, Lucie Oberic, Fontanet Bijou, Jean Valère Malfuson, Sarah Péricart, Camille Laurent, Julie Abraham, René-Olivier Casasnovas, Franck Morschhauser, Aspasia Stamatoullas-Bastard, Marie Maerevoet, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Institut Bergonié [Bordeaux], UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre de Transfusion Sanguine des Armées (CTSA), Service de Santé des Armées, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jules Bordet, CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, and Institut Bergonié - CRLCC Bordeaux
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0301 basic medicine ,re-sensitization ,medicine.medical_specialty ,medicine.medical_treatment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,chemotherapy ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Refractory ,Internal medicine ,medicine ,Refractory Hodgkin Lymphoma ,Progression-free survival ,Brentuximab vedotin ,Chemotherapy ,business.industry ,Hematology ,Immunotherapy ,medicine.disease ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,anti-PD-1 ,immunotherapy ,business ,Progressive disease ,Hodgkin lymphoma ,medicine.drug - Abstract
IF 5.303; International audience; Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti-PD-1 therapy, assessed by PET-CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pre-treated before anti-PD-1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti-PD1 therapy were progressive disease (PD) (n=24) and partial response (PR) (n=6). For the 24 PD patients, median anti-PD-1 related PFS was 7.5 months (95%CI, 5.7-11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti-PD-1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow-up of 12.1 months (7-14.7), the median PFS following the initiation of CT was 11 months (95%CI, 6.3; not reached) and the median of overall survival was not reached. These observations in highly pre-treated HL patients suggest that anti-PD-1 therapy might re-sensitize tumor cells to CT. This article is protected by copyright. All rights reserved.
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- 2018
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39. Somatic mutations of cell-free circulating DNA detected by targeted next-generation sequencing and digital droplet PCR in classical Hodgkin lymphoma
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Marie Cornic, Catherine Maingonnat, Lucile Bessi, Pascaline Etancelin, Pierre-Julien Viailly, Philippe Bertrand, Ludivine Beaussire, Philippe Ruminy, Aspasia Stamatoullas, Vincent Camus, NasrinSarafan Vasseur, Elodie Bohers, Jean-Michel Picquenot, Hervé Tilly, Fabrice Jardin, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), service d'anatomo-pathologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), and Service d'hématologie
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Cancer Research ,Somatic cell ,[SDV]Life Sciences [q-bio] ,macromolecular substances ,Cell free ,Biology ,Polymerase Chain Reaction ,DNA sequencing ,Circulating Tumor DNA ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,immune system diseases ,hemic and lymphatic diseases ,polycyclic compounds ,Classical Hodgkin lymphoma ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Digital droplet pcr ,Genetic Association Studies ,ComputingMilieux_MISCELLANEOUS ,food and beverages ,High-Throughput Nucleotide Sequencing ,Hematology ,DNA, Neoplasm ,Hodgkin Disease ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Circulating DNA ,030215 immunology - Abstract
Classical Hodgkin lymphoma (cHL) accounts for 30% of all lymphomas [1]. Currently, 20–25% of cHL cases relapse or are refractory after first-line standard treatments, leading to the need to better ...
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40. Prolonged remissions after anti-PD1 discontinuation in patients with Hodgkin lymphoma
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Guillaume Manson, Krimo Bouabdallah, Aspasia Stamatoullas, Pauline Brice, Laurent Dercle, Hervé Ghesquières, Charles Herbaux, Roch Houot, Jean-Marc Schiano, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP), Institut Paoli Calmettes, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Programmed Cell Death 1 Receptor ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biochemistry ,Gastroenterology ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,Cohort Studies ,Young Adult ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Refractory ,Internal medicine ,medicine ,Humans ,Young adult ,Prospective cohort study ,ComputingMilieux_MISCELLANEOUS ,Aged ,biology ,business.industry ,Remission Induction ,Cell Biology ,Hematology ,Middle Aged ,Hodgkin Disease ,3. Good health ,Discontinuation ,Nivolumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Hodgkin lymphoma ,Female ,Antibody ,business ,Cohort study - Abstract
To the editor: Anti-programmed cell death protein 1 (anti-PD-1) antibodies demonstrated remarkable efficacy in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). In the 2 largest prospective studies that evaluated the anti-PD-1 antibodies nivolumab (CHECKMATE-205)[1][1] and
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41. Cyberlindnera jadinii (teleomorph Candida utilis) candidaemia in a patient with aplastic anaemia: a case report
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Hélène Lanic, Vincent Camus, Stéphane Leprêtre, Gilles Gargala, Emilie Lemasle, Aspasia Stamatoullas, Marion David, Nathalie Contentin, Pascal Lenain, Hervé Tilly, Pauline Treguier, Anne-Lise Menard, Fabrice Jardin, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Rouen, Normandie Université (NU), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), VILLIER, Venceslas, Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Microbiology (medical) ,Antifungal ,medicine.medical_specialty ,medicine.drug_class ,Case Report ,Case presentation ,Microbiology ,Cyberlindnera ,03 medical and health sciences ,0302 clinical medicine ,medullary aplasia ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Internal medicine ,Medicine ,candidaemia ,Cyberlindnera jadinii ,Pichia ,Torulopsis utilis ,biology ,Adult patients ,business.industry ,Septic shock ,Blood/heart and Lymphatics ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,medicine.disease ,biology.organism_classification ,3. Good health ,Transplantation ,030220 oncology & carcinogenesis ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,business ,030215 immunology - Abstract
International audience; Introduction. We present what is believed to be the first report of candidaemia caused by Cyberlindnera (Pichia) jadinii (teleomorph of Candida utilis) in a patient with an aplastic anaemia.Case presentation. The patient, a 21-year-old male, presented with hepatic cytolysis, cutaneous and pulmonary involvement, and septic shock. Cyberlindnera jadinii was identified by aerobic blood culture and MS. The patient initially received multiple and combined antifungal therapy, but continued to have persistent skin lesions and fever. He was successfully treated by emergency haploidentical haematopoietic stem cell transplantation, combined with triple antifungal therapy and supportive care.Conclusion. Cyberlindnera jadinii, teleomorph of Candida utilis, which is not usually invasive, can lead to an opportunistic invasive infection in unhealthy adult patients. For treatment of the invasive candida infection, it is necessary to combine antifungal therapy and supportive care.
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- 2018
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42. Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by the Groupe Francophone Des Myélodysplasies
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Marie Sebert, Hervé Dombret, Norbert Vey, Sylvie Chevret, Mathilde Hunault, Lionel Ades, Pierre Fenaux, Aspasia Stamatoullas, Emmanuel Raffoux, Andrea Toma, Romain Guieze, Laure Stalnikiewicz, Christian Recher, Eric Wattel, Cendrine Chaffaut, Claude Gardin, Thomas Prebet, Krimo Bouabdallah, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Mohamed Boudiaf de M'sila, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematology (IPC-Marseille), Hôpital Avicenne [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, CRLCC Henri Becquerel, Service d'hématologie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital avicenne, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer [Boulogne] (INCA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)
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Acute Myeloid Leukemia ,Adult ,Male ,medicine.medical_specialty ,Acute myeloblastic leukemia ,Population ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,education ,Lenalidomide ,ComputingMilieux_MISCELLANEOUS ,Aged ,education.field_of_study ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Articles ,Middle Aged ,medicine.disease ,Prognosis ,3. Good health ,Thalidomide ,Transplantation ,Leukemia ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Myelodysplastic Syndromes ,Immunology ,Chromosomes, Human, Pair 5 ,Female ,Chromosome Deletion ,business ,030215 immunology ,medicine.drug - Abstract
Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within a complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with intensive chemotherapy in a phase II study. Treatment consisted of daunorubicin (45 mg/m2/day, days 1-3 in cohort 1, escalated to 60 mg/m2/day, days 1-3 in cohorts 2 and 3) combined with cytosine arabinoside (200 mg/m2/day, days 1-7) and lenalidomide (10 mg/day, days 1-21 in cohorts 1 and 2, escalated to 25 mg/day, days 1-21 in cohort 3). Eighty-two patients with 5q deletion were enrolled, including 62 with acute myeloblastic leukemia, 62/79 (78%) of whom had a complex karyotype (median 7 cytogenetic abnormalities, all but 2 of them monosomal) and three had unknown karyotypes. Thirty-eight patients (46%) achieved complete remission and the overall response rate was 58.5%. Among the 62 patients with a complex karyotype, 27 achieved complete remission (44%) and 21 had cytogenetic responses. A lower response rate was observed in patients with acute myeloblastic leukemia but other pretreatment factors, including cytogenetic complexity and treatment cohort, did not significantly influence response. Fifteen patients underwent allogeneic stem cell transplantation, including 11 patients in first remission. The 1-year cumulative incidence of relapse was 64.6% and the median overall survival was 8.2 months. By comparison with conventional intensive chemotherapy, the treatment protocol we used appeared to produce higher hematologic and cytogenetic complete remission rates in patients with very poor cytogenetics, but response duration was short in this very poor risk population, highlighting the need for better post-induction strategies. Clinical trial registry number: NCT00885508.
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- 2017
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43. Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma
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Marie J Chammas, Emily Pesek, Robert J. Soiffer, Veronika Bachanova, Abraham Avigdor, Joseph H. Antin, Armando Santoro, Philippe Armand, Willy Lescaut, Anne Thiebaut-Bertrand, Stephen M. Ansell, Jerome Ritz, Pier Luigi Zinzani, Reid W. Merryman, Ahmad Halwani, Miguel-Angel Perales, Scott C. Bresler, Harim Kim, L. Castagna, Amitabh Srivastava, Vincent T. Ho, Haesook T. Kim, Roch Houot, Aspasia Stamatoullas-Bastard, Carol Reynolds, Pierre-Simon Rohrlich, Carmelo Carlo-Stella, Nathalie Dhedin, Hélène Labussière Wallet, Tony Marchand, Sylvie François, Merryman, Reid W., Kim, Haesook T., Zinzani, Pier Luigi, Carlo-Stella, Carmelo, Ansell, Stephen M., Perales, Miguel-Angel, Avigdor, Abraham, Halwani, Ahmad S., Houot, Roch, Marchand, Tony, Dhedin, Nathalie, Lescaut, Willy, Thiebaut-Bertrand, Anne, François, Sylvie, Stamatoullas-Bastard, Aspasia, Rohrlich, Pierre-Simon, Wallet, Hélène Labussière, Castagna, Luca, Santoro, Armando, Bachanova, Veronika, Bresler, Scott C., Srivastava, Amitabh, Kim, Harim, Pesek, Emily, Chammas, Marie, Reynolds, Carol, Ho, Vincent T., Antin, Joseph H., Ritz, Jerome, Soiffer, Robert J., Armand, Philippe, Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital l'Archet, Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Department of Oncology and Hematology, Humanitas Cancer Center, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Harvard Medical School [Boston] (HMS), Seoul National University College of Medicine, Dana-Farber Cancer Institute [Boston], L. and A. Seràgnoli Hospital, University of Bologna, University of Milan, Mayo Clinic [Rochester], Memorial Sloane Kettering Cancer Center [New York], Chaim Sheba Medical Center, Huntsman Cancer Institute [Salt Lake City], University of Utah, Université de Rennes (UR)-Hôpital Pontchaillou, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Università degli Studi di Milano = University of Milan (UNIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and University of Minnesota [Twin Cities]
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Adult ,Male ,medicine.medical_specialty ,Lymphoma ,medicine.medical_treatment ,Immunology ,Programmed Cell Death 1 Receptor ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,Hematopoietic stem cell transplantation ,Kaplan-Meier Estimate ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Biochemistry ,Disease-Free Survival ,Statistics, Nonparametric ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Cytotoxic T cell ,Humans ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Hematology ,Cell Biology ,Middle Aged ,medicine.disease ,Allografts ,Combined Modality Therapy ,3. Good health ,Blockade ,Nivolumab ,030220 oncology & carcinogenesis ,Monoclonal ,Female ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
International audience; Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1(+) T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade.
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44. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome
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Amandine Baptiste, Thibaud Lefebvre, Olivier Ernst, Emmanuelle Chauzit, Jean-Pierre Vannier, Agnès Guerci-Bresler, Christian Rose, Zoubida Karim, Hervé Puy, Aspasia Stamatoullas, Mariane De Montalembert, Valentine Brousse, Krimo Bouabdallah, Mohamed Touati, C. Dumesnil, Agnès Lahary, Marina Cavazzana, Caroline Elie, Jean-Antoine Ribeil, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre de Référence de la Drépanocytose-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Département de Biothérapie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'informatique médicale et biostatistiques [CHU Necker], Radiologie interventionnelle, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie, Hôpital Saint-Vincent-de-Paul, TAN, Yossan-Var, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence de la Drépanocytose, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Male ,Blood transfusion ,Physiology ,Thalassemia ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Gastroenterology ,Physical Chemistry ,Biochemistry ,Diagnostic Radiology ,0302 clinical medicine ,hemic and lymphatic diseases ,Medicine and Health Sciences ,Erythropoiesis ,10. No inequality ,Child ,lcsh:Science ,Multidisciplinary ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,biology ,Chelation ,Radiology and Imaging ,Heart ,Hematology ,Middle Aged ,Magnetic Resonance Imaging ,Sickle cell anemia ,Clinical Laboratory Sciences ,3. Good health ,[SDV] Life Sciences [q-bio] ,Chemistry ,Genetic Diseases ,030220 oncology & carcinogenesis ,Physical Sciences ,Female ,Anatomy ,Research Article ,Adult ,medicine.medical_specialty ,Iron Overload ,Adolescent ,Anemia ,Imaging Techniques ,Iron ,Anemia, Sickle Cell ,Research and Analysis Methods ,Iron Chelating Agents ,03 medical and health sciences ,Autosomal Recessive Diseases ,Hepcidin ,Diagnostic Medicine ,Internal medicine ,medicine ,Humans ,Blood Transfusion ,Clinical Genetics ,Ferritin ,Sickle Cell Disease ,Chemical Bonding ,business.industry ,Transfusion Medicine ,Myelodysplastic syndromes ,Myocardium ,lcsh:R ,Biology and Life Sciences ,Proteins ,Protein Complexes ,medicine.disease ,Hematopoiesis ,Hemoglobinopathies ,Myelodysplastic Syndromes ,biology.protein ,Cardiovascular Anatomy ,lcsh:Q ,business ,Physiological Processes ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P
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45. Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial
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Richard W.M. van der Maazen, Monica Bellei, Veronique Edeline, Marc André, Annibale Versari, Valeria Fiaccadori, Catherine Sebban, Alessandro Re, Massimo Federico, Pauline Brice, Richard Delarue, Catherine Fortpied, Christophe Fermé, Martin Hutchings, Olivier Casasnovas, Oumedaly Reman, Tiana Raveloarivahy, Michel Meignan, Aspasia Stamatoullas, Reda Bouabdallah, Manuel Gotti, Gustaaf W. van Imhoff, Francesco Merli, Theodore Girinsky, Lena Specht, John M. M. Raemaekers, Institut Gustave Roussy ( IGR ), Institut d'Hématologie de Basse-Normandie ( IHBN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen-Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), European Organisation for Research and Treatment of Cancer [Bruxelles] ( EORTC ), European Cancer Organisation [Bruxelles] ( ECCO ), Equipe SAPHIHR (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire de Psychologie et NeuroCognition ( LPNC ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Grenoble Alpes ( UGA ), Haematology, University Medical Center Groningen, Département d'Hematologie, Institut Paoli Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CRLCC Henri Becquerel, Service d'hématologie biologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Rigshospitalet [Copenhagen], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Department of Haematology, Radboud University Medical Center [Nijmegen], Institut Paoli-Calmettes, Service d'immuno-hématologie pédiatrique [CHU Necker], Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)
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Male ,Cancer Research ,Procarbazine ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Disease ,Survivors ,Etoposide ,Radiation ,Chemoradiotherapy ,Middle Aged ,Hodgkin Disease ,Vinblastine ,Dacarbazine ,Survival Rate ,Oncology ,Vincristine ,Interim-Pet ,030220 oncology & carcinogenesis ,Female ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,medicine.drug ,Adult ,Adolescent ,Guidelines ,Increased Risk ,Disease-Free Survival ,Bleomycin ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,Chemotherapy ,Cyclophosphamide ,Survival rate ,Aged ,Neoplasm Staging ,Radiotherapy ,business.industry ,ABVD ,Group Hd14 Trial ,Doxorubicin ,Positron-Emission Tomography ,Prednisone ,Therapy ,business ,Nuclear medicine ,030215 immunology - Abstract
Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated—according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)—stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET—361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.
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46. Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents
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Jennifer Kaivers, Ulrich Germing, Rosa Sapena, Giovanni Cametti, Mikkael A. Sekeres, Katharina Götze, Maria Diez Campelo, Agnès Guerci-Bresler, Fabrizio Pane, Stéphane Cheze, François Dreyfus, Teresa Bernal, Enrico Balleari, David P. Steensma, Rami S. Komrokji, Pierre Fenaux, Christian Rose, Guillermo Sanz, Valeria Santini, Catharina Müller-Thomas, Marisa Calabuig, Aspasia Stamatoullas, Norbert Vey, Dario Ferrero, Alessandro Sanna, Jean Francois Hamel, Jaime Fensterl, Dominique Bordessoule, Ioannis Kotsianidis, Sophie Park, Andrea Toma, Charikleia Kelaidi, Gail J. Roboz, Fernando Ramos, Gianluca Gaidano, Sylvain Thepot, Odile Beyne-Rauzy, Pascale Cony-Makhoul, Eric Wattel, Daniela Gioia, Park, Sophie, Hamel, Jean Françoi, Toma, Andrea, Kelaidi, Charikleia, Thépot, Sylvain, Campelo, Maria Diez, Santini, Valeria, Sekeres, Mikkael A, Balleari, Enrico, Kaivers, Jennifer, Sapena, Rosa, Götze, Katharina, Müller Thomas, Catharina, Beyne Rauzy, Odile, Stamatoullas, Aspasia, Kotsianidis, Ioanni, Komrokji, Rami, Steensma, David P, Fensterl, Jaime, Roboz, Gail J, Bernal, Teresa, Ramos, Fernando, Calabuig, Marisa, Guerci Bresler, Agnè, Bordessoule, Dominique, Cony Makhoul, Pascale, Cheze, Stéphane, Wattel, Eric, Rose, Christian, Vey, Norbert, Gioia, Daniela, Ferrero, Dario, Gaidano, Gianluca, Cametti, Giovanni, Pane, Fabrizio, Sanna, Alessandro, Germing, Ulrich, Sanz, Guillermo F, Dreyfus, Françoi, and Fenaux, Pierre
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Male ,Cancer Research ,0302 clinical medicine ,Recurrence ,Risk Factors ,hemic and lymphatic diseases ,Hydroxyurea ,Cumulative incidence ,Treatment Failure ,Enzyme Inhibitors ,Lenalidomide ,Aged, 80 and over ,Cytarabine ,Anemia ,Middle Aged ,Thalidomide ,Melodysplastic syndrome ,Survival Rate ,Leukemia, Myeloid, Acute ,Oncology ,International Prognostic Scoring System ,030220 oncology & carcinogenesis ,Retreatment ,Azacitidine ,Cyclosporine ,Disease Progression ,Chromosomes, Human, Pair 5 ,Female ,Chromosome Deletion ,Erythrocyte Transfusion ,medicine.drug ,medicine.medical_specialty ,Melodysplastic syndrome, erytropoiesis stimulating agents, 5q ,erytropoiesis stimulating agents ,Decitabine ,Antineoplastic Agents ,Tretinoin ,Lower risk ,5q ,Arsenic ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Survival rate ,Aged ,Antilymphocyte Serum ,Retrospective Studies ,business.industry ,Valproic Acid ,Myelodysplastic syndromes ,Retrospective cohort study ,medicine.disease ,Myelodysplastic Syndromes ,Hematinics ,Physical therapy ,business ,030215 immunology - Abstract
Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.
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47. Infradiaphragmatic Hodgkin lymphoma: a large series of patients staged with PET-CT
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Sylvain Garciaz, Hervé Ghesquières, Lauriane Filliatre, Morgane Mounier, Cédric Rossi, Emmanuelle Nicolas-Virelizier, Gilles Salles, Rene-Olivier Casasnovas, Adrien Chauchet, Pauline Brice, Violaine Safar, Philippe Rey, Marion Alcantara, Bertrand Coiffier, Aspasia Stamatoullas-Bastard, Aurore Perrot, Emilie Reboursiere, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Institut National Polytechnique [Toulouse] ( INP ) -Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire de Psychologie et NeuroCognition ( LPNC ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Grenoble Alpes ( UGA ), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Léon Bérard [Lyon], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Benemérita Universidad Autónoma de Puebla ( BUAP ), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, CHU Caen, Laboratoire Bordelais de Recherche en Informatique ( LaBRI ), Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique [Toulouse] (INP), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Laboratoire de Psychologie et NeuroCognition (LPNC), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Benemérita Universidad Autónoma de Puebla (BUAP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
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medicine.medical_specialty ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Computed tomography ,Stage ii ,infradiaphragmatic ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,0302 clinical medicine ,medicine ,In patient ,Stage (cooking) ,radiotherapy ,ComputingMilieux_MISCELLANEOUS ,Gynecology ,PET-CT ,medicine.diagnostic_test ,business.industry ,Large series ,Oncology ,ABVD ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,business ,030217 neurology & neurosurgery ,Research Paper ,medicine.drug - Abstract
// Cedric Rossi 1, 2 , Morgane Mounier 3 , Pauline Brice 4 , Violaine Safar 5 , Emmanuelle Nicolas-Virelizier 6 , Philippe Rey 6 , Aspasia Stamatoullas-Bastard 7 , Marion Alcantara 7 , Adrien Chauchet 8 , Emilie Reboursiere 9 , Lauriane Filliatre 10 , Aurore Perrot 10 , Sylvain Garciaz 11 , Gilles Salles 6 , Bertrand Coiffier 6 , Herve Ghesquieres 5, 6 and Rene-Olivier Casasnovas 1, 12 1 Hematologie Clinique, CHU Le Bocage, Dijon, France 2 INSERM UMR 1037 - Cancer Research Center of Toulouse, Toulouse, France 3 Registre des Hemopathies Malignes de Cote d’Or, EA4184, Universite de Bourgogne, Dijon, France 4 Hematologie Clinique, CHU Paris-GH St-Louis Lariboisiere F-Widal - Hopital Saint-Louis, Paris, France 5 Hematologie Clinique, Centre Hospitalier Lyon Sud, Pierre-Benite, France 6 Hematologie Clinique, Centre Regional de Lutte Contre le Cancer Leon Berard, Lyon, France 7 Hematologie Clinique, Centre Henri Becquerel, Rouen, France 8 Hematologie Clinique, CHU Besancon, Besancon, France 9 Hematologie Clinique, CHU Caen, Caen, France 10 Hematologie Clinique, CHRU Nancy, Nancy, France 11 Hematologie Clinique, Institut Paoli-Calmettes, Marseille, France 12 INSERM UMR 1231, Universite Bourgogne Franche-Comte, Dijon, France Correspondence to: Cedric Rossi, email: cedric.rossi66@gmail.com Keywords: Hodgkin lymphoma, infradiaphragmatic, radiotherapy Received: March 21, 2017 Accepted: June 19, 2017 Published: July 19, 2017 ABSTRACT Introduction: Infradiaphragmatic Hodgkin Lymphoma (IDHL) accounts for 3-11% of adult cases of stage I-II Hodgkin Lymphoma and the treatment strategy in IDHL is still heterogeneous. All previous published studies were conducted before the PET-CT era. PET may provide a more accurate evaluation of IDHL stage. The aim of this study was to analyze the clinical and biological characteristics of IDHL patients staged by CT scan or PET-CT in eight French hematology departments and their impact on outcomes in these patients. Methods: Baseline clinical and biological data and outcomes in patients with a first diagnosis of stage I-II IDHL treated with ABVD +/- radiotherapy were retrospectively collected. Results: Among the 99 patients included, 65 (66%) were staged with PET-CT. These patients were older (53 years vs 46 years, p=0.043), had lower ESR (27 vs 58mm, p=0.022), higher hemoglobin level (13.6 vs 12.8g/dL, p=0.015), less frequent Ann Arbor stage II (74% vs 91%) and less central adenopathy involvement (60% vs 82%, p=0.024). Treatment was chemotherapy alone in 55% of patients and the remaining patients received chemo-radiotherapy (CRT). Five-year PFS and OS rates in PET-CT-staged patients were 78% (95% CI 64-87) and 88% (95% CI 73-95), respectively, compared with 65% (p=0.225) and 82% (p=0.352) in CT-staged patients. The CRT strategy was associated with fewer relapses (p=0.027). Conclusion: This study showed that the characteristics of CT-staged IDHL patients were less favorable than those of PET-CT-staged patients and indicated that CRT provided better PFS than did chemotherapy alone.
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48. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association
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Diane Damotte, Aspasia Stamatoullas, Herve Ghesquieres, Laurent Martin, Camille Laurent, Peggy Dartigues, Pierre Hirsch, Thierry Jo Molina, Clémentine Sarkozy, Anne-Sophie Michallet, Jehan Dupuis, Bettina Fabiani, Alexandra Traverse-Glehen, Gilles Salles, Franck Morsschauser, Marie Maerevoet, M. Parrens, Maria Gomes da Silva, Krimo Bouabdallah, Bertrand Coiffier, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Léon Bérard [Lyon], CHU Henri Mondor, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy ( IGR ), CRLCC Henri Becquerel, Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Instituto Português de Oncologia de Lisboa Francisco Gentil, Institut Jules Bordet, Departement de Pathologie, Institut Claudius Regaud,Toulouse, Fédération Nationale des Centres de Lutte contre le Cancer, Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, Hospices Civils de Lyon ( HCL ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor [Créteil], Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Gustave Roussy (IGR), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)
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Male ,BEACOPP ,Biopsy ,medicine.medical_treatment ,Gastroenterology ,0302 clinical medicine ,Bone Marrow ,Recurrence ,immune system diseases ,hemic and lymphatic diseases ,Aged, 80 and over ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Articles ,Hematology ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Immunohistochemistry ,3. Good health ,Treatment Outcome ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Rituximab ,medicine.drug ,Adult ,medicine.medical_specialty ,Lymphoma, B-Cell ,Adolescent ,Mediastinal Neoplasms ,Gray zone lymphoma ,Immunophenotyping ,Young Adult ,03 medical and health sciences ,Internal medicine ,[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology ,Biomarkers, Tumor ,medicine ,Humans ,Survival analysis ,Aged ,Neoplasm Staging ,Retrospective Studies ,business.industry ,medicine.disease ,Survival Analysis ,Surgery ,Lymphoma ,Radiation therapy ,Regimen ,ABVD ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Follow-Up Studies ,030215 immunology - Abstract
International audience; Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lym-phoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalat-ed BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.
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- 2016
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49. Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma
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Sydney Dubois, Vincent Camus, Philippe Bertrand, Elodie Bohers, Jean Michel Picquenot, Pierre-Julien Viailly, Fabrice Jardin, Marie Cornic, Philippe Ruminy, Thierry Frebourg, Aspasia Stamatoullas, Christian Bastard, Liana Veresezan, Nasrin Sarafan-Vasseur, Sylvain Mareschal, Catherine Maingonnat, Pierre Vera, Hervé Tilly, Valérie Tallon-Simon, Stéphanie Becker, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), service d'anatomo-pathologie, Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), and Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques
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0301 basic medicine ,Male ,Receptors, Cytoplasmic and Nuclear ,medicine.disease_cause ,0302 clinical medicine ,Recurrence ,immune system diseases ,Neoplasms ,Positron Emission Tomography Computed Tomography ,hemic and lymphatic diseases ,Mutation ,medicine.diagnostic_test ,High-Throughput Nucleotide Sequencing ,Hematology ,DNA, Neoplasm ,Articles ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Hodgkin Disease ,3. Good health ,Tumor Burden ,Treatment Outcome ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,Adult ,Context (language use) ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Karyopherins ,03 medical and health sciences ,Young Adult ,Germline mutation ,Cell Line, Tumor ,Biopsy ,medicine ,Biomarkers, Tumor ,Humans ,Codon ,Survival analysis ,Neoplasm Staging ,Retrospective Studies ,medicine.disease ,Minimal residual disease ,Survival Analysis ,Lymphoma ,030104 developmental biology ,Amino Acid Substitution ,Cancer research - Abstract
International audience; Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma, in biopsies and plasma circulating cell-free DNA from patients with classical Hodgkin lymphoma using a highly sensitive digital PCR technique. A total of 94 patients were included in the present study. This widely expressed XPO1 E571K mutation is present in one quarter of classical Hodgkin lymphoma patients (24.2%). Mutated and wild-type classical Hodgkin lymphomas were similar regarding the main clinical features. Patients with a detectable XPO1 mutation at the end of treatment displayed a tendency toward shorter progression-free survival, as compared to patients with undetectable mutation in plasma cell-free DNA (2-year progression-free survival: 57.1%, 95% confidence interval: 30.1-100% versus 2-year progression-free survival: 90.5%, 95% confidence interval: 78.8-100%, respectively, P=0.0601). To conclude, the detection of the XPO1 E571K mutation in biopsy and plasma cell-free DNA by digital PCR may be used as a novel biomarker in classical Hodgkin lymphoma for both diagnosis and minimal residual disease, and pinpoints a crucial role of XPO1 in classical Hodgkin lymphoma pathogenesis. The detection of somatic mutation in the plasma cell-free DNA of patients represents a major technological advance in the context of liquid biopsies and noninvasive management of classical Hodgkin lymphoma.
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- 2016
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50. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion
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Anne Banos, Celia Salanoubat, Odile Beyne-Rauzy, Aline Renneville, Claude Preudhomme, Pascale Cony-Makhoul, Stefan Wickenhauser, Christian Rose, Eric Wattel, Denis Caillot, Julie Lejeune, Francois Dreyfus, François Guilhot, G. Tertian, Agnès Guerci-Bresler, S. Nimuboma, Françoise Isnard, Laurence Sanhes, Kamel Laribi, Stéphane Cheze, Michaela Fontenay, R. Benramdane, B. de Renzis, Dominique Bordessoule, Borhane Slama, Kamal Bouabdallah, Veronique Sardnal, B. Chouffi, Berengere Gruson, Anne-Laure Taksin, Andrea Toma, Sylvie Chevret, Laurence Legros, Karim Maloum, Emmanuel Gyan, R. Petit, C. Gardin, Olivier Kosmider, Carole Soussain, Aspasia Stamatoullas, Jacques Delaunay, Pierre Fenaux, Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Laboratoire d'Hématologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Strasbourg, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Le Mans (CH Le Mans), CHU Amiens-Picardie, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hôpital Avicenne [AP-HP], Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, Centre hospitalier de Boulogne sur mer, Hôpital de Corbeil-ESsonnes, Centre Hospitalier René Dubos [Pontoise], Centre Hospitalier Universitaire de Nice (CHU de Nice), Virologie et pathogenèse virale (VPV), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Bordeaux [Bordeaux], INSERM CIC 0802 (INSERM - CHU de Poitiers), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Centre Hospitalier de Versailles André Mignot (CHV), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], CRLCC René Huguenin, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), [Institut Cochin] Departement Infection, immunité, inflammation, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), CRLCC Henri Becquerel, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Le MAns, Hôpital Universitaire d'Amiens, Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), Centre Hospitalier d'Avignon ( CHA ), Hôpital Avignon, Centre Hospitalier Universitaire de Nice ( CHU de Nice ), Virologie et pathogenèse virale ( VPV ), Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Centre Hospitalier Universitaire de Bordeaux, INSERM CIC 0802 ( INSERM CIC 0802, CHU de Poitiers ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de Versailles (CHV), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Département d’Immunologie Biologique [AP-HP - Hôpital Saint-Antoine, Paris], Unité d’autoimmunité, AP-HP - Hôpital Saint-Antoine -AP-HP - Hôpital Saint-Antoine, Centre Hospitalier Régional Universitaire de Tours, CHRU Tours, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Cochin [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Centre Hospitalier d'Avignon (CHA), INSERM CIC 0802 (INSERM CIC 0802, CHU de Poitiers), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), and Jonchère, Laurent
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Male ,Cancer Research ,[SDV]Life Sciences [q-bio] ,Angiogenesis Inhibitors ,Gastroenterology ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology ,Prospective Studies ,Lenalidomide ,Hematology ,Anemia ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Middle Aged ,Prognosis ,3. Good health ,Thalidomide ,[SDV] Life Sciences [q-bio] ,Leukemia ,Oncology ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 5 ,Drug Therapy, Combination ,Female ,Chromosome Deletion ,medicine.drug ,medicine.medical_specialty ,medicine.drug_class ,Lower risk ,03 medical and health sciences ,Refractory ,Internal medicine ,medicine ,Humans ,Blood Transfusion ,Erythropoietin ,Aged ,Neoplasm Staging ,[ SDV ] Life Sciences [q-bio] ,business.industry ,Erythropoiesis-stimulating agent ,medicine.disease ,Surgery ,Myelodysplastic Syndromes ,business ,030215 immunology ,Follow-Up Studies - Abstract
International audience; After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA
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- 2016
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