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1. PD-1 blockade and allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma, a matter of time: a national study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire

Author: Eleonore Kaphan, Francois Bettega, Nicolas Vallet, Nathalie Fegueux, Marie Robin, Ali Bazarbachi, Stephanie Nguyen, David Beauvais, Edouard Forcade, Maria Carolina Montes De Oca, Raynier Devillier, Patrice Chevallier, Michael Loschi, Anne Huynh, Jacques-Olivier Bay, Marie-Therese Rubio, Felipe Suarez, Sylvie Francois, Xavier Poire, Nathalie Contentin, Deborah Desmier, Amandine Charbonnier, Jerome Cornillon, Sylvain Chantepie, Pascal Turlure, Claude-Eric Bulabois, David Michonneau, Alban Villate, and SFGM-TC
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Not available.
Published: 2024
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2. Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry

Author: Claire Lacan, Jérôme Lambert, Edouard Forcade, Marie Robin, Patrice Chevallier, Sandrine Loron, Claude-Éric Bulabois, Corentin Orvain, Patrice Ceballos, Etienne Daguindau, Amandine Charbonnier, Yves Chalandon, Marc Bernard, Célestine Simand, Marie-Thérèse Rubio, Pascal Turlure, Johan Maertens, Anne Huynh, Michael Loschi, Jacques-Olivier Bay, Gaëlle Guillerm, Mustafa Alani, Cristina Castilla-Llorente, Xavier Poiré, Sylvain Chantepie, Natacha Maillard, Yves Beguin, Ambroise Marçais, Jérôme Cornillon, Jean-Valère Malfuson, Sébastien Maury, Nathalie Meuleman, Alban Villate, Mohammed-Amine Bekadja, Anouk Walter-Petrich, Nathalie Jacque, Micha Srour, Raynier Devillier, and Stéphanie Nguyen
Subjects: Haploidentical hematopoietic stem cell transplantation, Graft source, Bone marrow, Peripheral stem cell, Anti-thymoglobulin, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II–IV and III–IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III–IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II–IV; 16% for aGVHD III–IV) than with BM (28% for aGVHD II–IV; 8% for aGVHD III–IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III–IV remained higher with PB than with BM graft (HR = 2.0; range [1.17–3.43], p = 0.012).
Published: 2024
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3. PB1819: KMT2A::ARHGEF12 RARE FUSION ASSOCIATED WITH A NOVEL GERMLINE DDX41 VARIANT IN ACUTE MYELOID LEUKEMIA

Author: Maxime Roubinet, David Rizzo, Jasmine Chauzeix, Pascal Turlure, Marie-Pierre Laforet, Paco Derouault, Jean Feuillard, Catherine Yardin, Marie-Mathilde Auboiroux, Léa Veyrune, Alexandre Perani, Sylvie Bourthoumieu, Benjamin Dauriat, and Nathalie Gachard
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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4. Hereditary predisposition to malignant myeloid hemopathies: Caution in use of saliva and guideline based on our experience

Author: Alexandre Perani, Sylvie Bourthoumieu, David Rizzo, Jasmine Chauzeix, Benjamin Dauriat, Pascal Turlure, Stéphane Girault, Léa Veyrune, Maxime Roubinet, Jean Feuillard, Catherine Yardin, and Nathalie Gachard
Subjects: myeloid hemopathies, predisposition, saliva, DDX41, genetic counseling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: BackgroundPredisposition to myeloid malignancies is a field at the border of hematology and genetics. Knowledge in this domain has so rapidly increased that WHO defined in 2016 the new “Myeloid Neoplasms with Germline Predisposition” category of tumors. High throughput sequencing is frequently performed in tumors either for diagnosis or prognosis, but this approach may identify potential germline variants that have to be confirmed on non-infiltrated tissues.MethodIn this study, we systematically compared NGS data from genetic analysis performed on all sample types (bone marrow, blood, saliva, skin fibroblasts and hair follicles) in 29 patients, and 44 of their relatives (blood and saliva).ResultsWe showed that saliva was usable for relatives, but only for 24% (7/29) of our patients. Most of patients’ saliva were either “non-contributive” (14/29 i.e., 48% because clearly or probably infiltrated) or “inconclusive” (8/29 corresponding to 28%).ConclusionThe recommendations for the use of saliva we present here focus on the importance of collecting saliva during remission when possible. Moreover, we propose hair follicles as an alternative to skin biopsy, that remains the gold standard especially in case of allogenic hematopoietic stem cells transplantation. Technological progresses have revolutionized the diagnosis of predisposition to solid or hematological malignancies, and it is very likely that new techniques will help to manage the familial predisposition in the future.
Published: 2023
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5. Kinetics of early and late molecular recurrences after first-line imatinib cessation in chronic myeloid leukemia: updated results from the STIM2 trial

Author: Stéphanie Dulucq, Franck E. Nicolini, Delphine Rea, Pascale Cony-Makhoul, Aude Charbonnier, Martine Escoffre-Barbe, Valérie Coiteux, Pascal Lenain, Françoise Rigal-Huguet, Jixing Liu, Agnès Guerci-Bresler, Laurence Legros, Jean-Christophe Ianotto, Martine Gardembas, Pascal Turlure, Viviane Dubruille, Philippe Rousselot, Juliana Martiniuc, Henry Jardel, Hyacinthe Johnson-Ansah, Bertrand Joly, Tawfiq Henni, Emilie Cayssials, Patricia Zunic, Marc G. Berger, Bruno Villemagne, Fanny Robbesyn, Stephane Morisset, François-Xavier Mahon, and Gabriel Etienne
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia is feasible in clinical practice based on recently published international recommendations. Nevertheless, factors predictive of molecular recurrence have not been fully elucidated and long-term follow-up of patients enrolled in clinical studies are required in order to update knowledge on discontinuation attempts particularly in terms of the safety and durability of treatment-free remission (TFR). In the current study, we updated results from the STIM2 study in the light of the consensual criterion of molecular recurrence reported in different international recommendations. Among the 199 patients included in the perprotocol study, 108 patients lost a major molecular response. With a median follow-up of 40.8 months (5.5-111 months), the probability of treatment-free remission was 43.4% [36.3-50.4] at 5 years, 40.9% [32.8-47.3] at 7 years and 34.5% [25.6- 43.3] at 9 years. Molecular recurrence occurred between 0 to 6 months, 6 to 24 months and after 24 months in 75 patients (69%), 15 patients (14%) and 18 patients (17%), respectively. Notably, the kinetics of molecular recurrence differed significantly between these three subgroups with a median time from loss of MR4 (BCR::ABL1 IS≤0.01%) to loss of major molecular response of 1, 7 and 22 months, respectively. Predictive factors of molecular recurrence differed according to the time of occurrence of the molecular recurrence. Durations of imatinib treatment and deep molecular response as well as BCR::ABL1/ABL1 levels at cessation of tyrosine kinase inhibitor treatment, as quantified by reverse transcriptase droplet digital polymerase chain reaction, are involved in molecular recurrence occurring up to 24 months but not beyond. (ClinicalTrial. gov Identifier NCT#0134373).
Published: 2022
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6. Minimal residual disease monitoring in acute myeloid leukemia with non-A/B/D-NPM1 mutations by digital polymerase chain reaction: feasibility and clinical use

Author: Auriane Lesieur, Xavier Thomas, Olivier Nibourel, Nicolas Boissel, Laurène Fenwarth, Stéphane De Botton, Elise Fournier, Karine Celli-Lebras, Emmanuel Raffoux, Christian Recher, Juliette Lambert, Céline Berthon, Arnaud Pigneux, Raphael Itzykson, Pascal Turlure, Cécile Pautas, Jacques Vargaftig, Claude Preudhomme, Hervé Dombret, and Nicolas Duployez
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2020
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7. Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation – a prospective, non-interventional study of the EBMT Transplant Complication Working Party

Author: Olaf Penack, Christophe Peczynski, Steffie van der Werf, Jürgen Finke, Arnold Ganser, Helene Schoemans, Jiri Pavlu, Riitta Niittyvuopio, Wilfried Schroyens, Leylagül Kaynar, Igor W. Blau, Walter van der Velden, Jorge Sierra, Agostino Cortelezzi, Gerald Wulf, Pascal Turlure, Montserat Rovira, Zubeydenur Ozkurt, Maria J. Pascual-Cascon, Maria C. Moreira, Johannes Clausen, Hildegard Greinix, Rafael F. Duarte, and Grzegorz W. Basak
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease (GvHD). In a clinical pilot trial, peri-transplant uric acid depletion reduced acute GvHD incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline comorbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence interval [CI]: 1.0–2.4, P=0.08). However, they had significantly shorter overall survival (HR 2.8, 95% CI: 1.7–4.7, P
Published: 2020
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8. Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial

Author: Olivier Tournilhac, Magali Le Garff-Tavernier, Stéphanie Nguyen Quoc, Edouard Forcade, Patrice Chevallier, Faezeh Legrand-Izadifar, Gandhi Laurent Damaj, David Michonneau, Cécile Tomowiak, Cécile Borel, Corentin Orvain, Pascal Turlure, Rabah Redjou, Gaëlle Guillerm, Laure Vincent, Celestine Simand, Richard Lemal, Claire Quiney, Patricia Combes, Bruno Pereira, Laure Calvet, Aurélie Cabrespine, Jacques-Olivier Bay, Véronique Leblond, Nathalie Dhédin, French Innovative Leukemia Organization (FILO), and Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing CLL. Minimal Residual Disease (MRD) assessment at 12 months post-HSCT is predictive of relapse. This phase 2 study aimed to achieve M12 MRD negativity (MRDneg) using MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed if failure by donor lymphocytes infusions. Patients had high-risk CLL according to 2006 EBMT consensus, in complete or partial response with lymphadenopathy < 5 cm and comorbidity score ≤ 2. Donors were HLA-matched sibling or matched unrelated (10/10). Forty-two enrolled patients with either 17p deletion (front-line, n=11; relapse n=16) or other high-risk relapse (n=15) received reduced intensity-conditioning regimen before HSCT and were submitted to Md-PII. M12-MRDneg status was achieved in 64% versus 14.2% before HSCT. With a median follow-up of 36 months (range, 19-53), 3-year overall survival, non-relapse mortality and cumulative incidence of relapse are 86.9% (95%CI, 70.8-94.4), 9.5% (95%CI, 3.7-23.4) and 29.6% (95%CI, 17.3-47.7). Incidence of 2-year limited and extensive chronic graft versus host disease (cGVHD) is 38% (95%CI, 23-53) and 23% (95%CI, 10-36) including 2 cases post Md-PII. Fifteen patients converted to MRDneg either after CsA withdrawal (n=12) or after cGVHD (n=3). As a time-dependent variable, MRDneg achievement at any time-point correlates with reduced relapse (HR=0.14 [0.04-0.53], p=0.004) and improvement of both progression free (HR=0.18 [0.06-0.6], p
Published: 2020
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9. Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT – A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

Author: Olaf Penack, Christophe Peczynski, Steffie van der Werf, Jürgen Finke, Arnold Ganser, Helene Schoemans, Jiri Pavlu, Riitta Niittyvuopio, Wilfried Schroyens, Leylagül Kaynar, Igor W. Blau, Walter J. F. M. van der Velden, Jorge Sierra, Agostino Cortelezzi, Gerald Wulf, Pascal Turlure, Montserrat Rovira, Zubeydenur Ozkurt, Maria J. Pascual-Cascon, Maria C. Moreira, Johannes Clausen, Hildegard Greinix, Rafael F. Duarte, and Grzegorz W. Basak
Subjects: transplantation, stem cell, immunology, biomarker, iron metabolism, ferritin, Immunologic diseases. Allergy, RC581-607
Abstract: Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 μg/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5–4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6–3.8, p < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2–3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5–6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6–9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.
Published: 2020
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10. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial

Author: Juliette Lambert, Cécile Pautas, Christine Terré, Emmanuel Raffoux, Pascal Turlure, Denis Caillot, Ollivier Legrand, Xavier Thomas, Claude Gardin, Karïn Gogat-Marchant, Stephen D. Rubin, Rebecca J. Benner, Pierre Bousset, Claude Preudhomme, Sylvie Chevret, Herve Dombret, and Sylvie Castaigne
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The randomized, phase III ALFA-0701 trial showed that a reduced and fractionated dose of gemtuzumab ozogamicin added to standard front-line chemotherapy significantly improves event-free survival (EFS) in adults with de novo acute myeloid leukemia (AML). Here we report an independent review of EFS, final overall survival (OS), and additional safety results from ALFA-0701. Patients (n=271) aged 50-70 years with de novo AML were randomized to receive conventional front-line induction chemotherapy (3+7daunorubicin+cytarabine) with/without gemtuzumab ozogamicin 3 mg/m2 on days 1, 4, and 7 during induction. Patients in remission following induction therapy received 2 courses of consolidation therapy (daunorubicin+cytarabine) with/without gemtuzumab ozogamicin (3 mg/m2/day on day 1) according to their initial randomization. The primary end point was investigator-assessed EFS. Secondary end points included OS and safety. A blinded independent review confirmed the investigator-assessed EFS results [August 1, 2011; hazard ratio (HR) 0.66; 95% Confidence Interval (CI): 0.49–0.89; 2-sided P=0.006], corresponding to a 34% reduction in risk of events in the gemtuzumab ozogamicin versus control arm. Final OS at April 30, 2013 favored gemtuzumab ozogamicin but was not significant. No differences in early death rate were observed between arms. The main toxicity associated with gemtuzumab ozogamicin was prolonged thrombocytopenia. Veno-occlusive disease (including after transplant) was observed in 6 patients in the gemtuzumab ozogamicin arm and 2 in the control arm. In conclusion, gemtuzumab ozogamicin added to standard intensive chemotherapy has a favorable benefit/risk ratio. These results expand front-line treatment options for adult patients with previously untreated AML. (Trial registered at clinicaltrials.gov; identifier: 00927498.)
Published: 2019
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11. Clofarabine versus fludarabine‐based reduced‐intensity conditioning regimen prior to allogeneic transplantation in adults with AML/MDS

Author: Patrice Chevallier, Myriam Labopin, Regis Peffault deLa Tour, Bruno Lioure, Claude‐Eric Bulabois, Anne Huynh, Didier Blaise, Pascal Turlure, Etienne Daguindau, Natacha Maillard, Ibrahim Yakoub‐Agha, Gaelle Guillerm, Jeremy Delage, Nathalie Contentin, Jacques‐Olivier Bay, Florence Beckerich, Jean‐Henri Bourhis, Marie Detrait, Stéphane Vigouroux, Sylvie François, Faezeh Legrand, Thierry Guillaume, Mohamad Mohty, and the SFGM‐TC
Subjects: Acute myeloid leukemia, allogeneic stem cell transplantation, clofarabine, fludarabine, myelodysplastic syndrome, reduced‐toxicity conditioning regimen, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM‐TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow‐up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60.8 years, AML 62%, CR1 69%, median follow‐up: 22.4 months) RIC regimen. In multivariate analysis, FB2A2 was associated with significant lower overall survival (OS, HR: 2.14; 95%CI: 1.05–4.35, P = 0.04) and higher relapse incidence (RI, HR: 2.17; 95%CI: 1.02–4.61, P = 0.04) and a trend for lower leukemia‐free survival (LFS, HR: 1.75; 95%CI: 0.94–3.26, P = 0.08). These results were confirmed using a propensity score‐matching strategy. However, when considering AML and MDS patients separately, the benefit of the CLOB2A2 regimen was restricted to AML patients (2‐year OS FB2A2: 38% [14.5–61.6] vs. CloB2A2: 79.2% [62.9–95.4], P = 0.01; 2‐year LFS FB2A2: 38% [16–59.9] vs. CloB2A2: 70.8% [52.6–89], P = 0.03). The better survivals were due to the lower risk of relapse in this CloB2A2 AML subgroup (2‐year RI FB2A2: 41.2% [19–62.4] vs. CloB2A2: 16.7% [5–34.2], P = 0.05). This retrospective comparison suggests that the CloB2A2 RIC regimen can likely provide longer survival than that awarded by a FB2A2 RIC regimen and may become a new standard of care RIC regimen for allotransplanted AML patients. A prospective phase 3 randomized study is warranted.
Published: 2016
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12. Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas

Author: Adèle de Masson, Marie Beylot-Barry, Jean-David Bouaziz, Régis Peffault de Latour, François Aubin, Sylvain Garciaz, Michel d’Incan, Olivier Dereure, Stéphane Dalle, Anne Dompmartin, Felipe Suarez, Maxime Battistella, Marie-Dominique Vignon-Pennamen, Jacqueline Rivet, Henri Adamski, Pauline Brice, Sylvie François, Séverine Lissandre, Pascal Turlure, Ewa Wierzbicka-Hainaut, Eolia Brissot, Rémy Dulery, Sophie Servais, Aurélie Ravinet, Reza Tabrizi, Saskia Ingen-Housz-Oro, Pascal Joly, Gérard Socié, Martine Bagot, and French Study Group on Cutaneous Lymphomas and Société Française de Greffe de Moëlle et Thérapie Cellulaire
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38–0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41–0.77) and progression-free survival 31% (95%CI: 0.19–0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1–0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3–6.2; P=0.01) but also transplant-related mortality (HR=10−7, 95%CI: 4.10−8−2.10−7; P
Published: 2014
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13. Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the Groupe Francophone des Myelodysplasies

Author: Lionel Adès, Fabien Le Bras, Marie Sebert, Charikleia Kelaidi, Thierry Lamy, François Dreyfus, Virginie Eclache, Jacques Delaunay, Didier Bouscary, Sorin Visanica, Pascal Turlure, Agnès Guerci Bresler, Marie-Paule Cabrol, Anne Banos, Michel Blanc, Norbert Vey, Alain Delmer, Eric Wattel, Sylvie Chevret, and Pierre Fenaux
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background Although lenalidomide is very effective in the treatment of anemia of lower risk myelodysplastic syndromes with 5q deletion (del 5q), concerns have been raised over the fact that this drug could trigger progression to acute myeloid leukemia in some patients.Design and Methods Ninety-five transfusion-dependent patients with lower risk myelodysplastic syndromes with del 5q were treated with lenalidomide (10 mg/day, for 3 weeks every 4 weeks); six (6.3%) of the patients progressed to acute myeloid leukemia. This cohort of 95 lenalidomide-treated patients was compared to a historical control cohort of 99 patients with lower risk myelodysplastic syndromes with del 5q who never received lenalidomide, using a propensity score approach that can control for potential confounders in non-randomized comparisons.Results The 4-year estimated cumulative incidence of leukemia was 9% in patients treated with lenalidomide and 15.8% in controls who did not receive lenalidomide (P=0.16).Conclusions Using a propensity score approach, we found no significant difference in acute myeloid leukemia progression and survival from diagnosis between the cohort treated with lenalidomide and the control cohort.
Published: 2012
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14. Impact of post-remission therapy in patients aged 65–70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria

Author: Raphael Itzykson, Claude Gardin, Cécile Pautas, Xavier Thomas, Pascal Turlure, Emmanuel Raffoux, Christine Terré, Pierre Fenaux, Sylvie Castaigne, Hervé Dombret, and Nicolas Boissel
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background There is no standard post-remission therapy in older patients with acute myeloid leukemia.Design and Methods From 1999 to 2006, the Acute Leukemia French Association group ran two concurrent randomized trials with overlapping inclusion criteria for patients aged 65 to 70 with acute myeloid leukemia, with different post-remission strategies: two intensive courses in the 9801 trial, one intensive course or six outpatient courses in the 9803 trial. We analyzed the outcome of these patients per protocol and per post-remission therapy.Results Two hundred and eleven patients aged 65 to 70 years with de novo acute myeloid leukemia were enrolled in trial 9801 (n=76) or 9803 (n=135). The patients in the two trials had comparable white blood cell counts (P=0.3), cytogenetics (P=0.49), and complete remission rates (70% and 57%, respectively; P=0.17). Overall survival was identical in both trials (32% and 34% at 2 years, respectively; P=0.71). Overall survival after complete remission was identical in the 103 of 130 patients who received the planned post-remission courses (n=44 with two intensive courses, n=28 with one intensive course, n=31 with six outpatient courses; 41%, 55%, and 58% at 2 years, respectively; P=0.34). Even in patients with favorable or normal karyotype (n=97), overall survival from complete remission was not improved by more intensive post-remission therapy.Conclusions In patients aged 65 to 70 years with de novo acute myeloid leukemia in complete remission after standard intensive induction chemotherapy, there is no apparent benefit from intensive post-remission therapy. (ClinicalTrials.gov Identifiers: NCT00931138 and NCT00363025)
Published: 2011
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15. A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

Author: Mathilde Hunault-Berger, Thibaut Leguay, Xavier Thomas, Ollivier Legrand, Françoise Huguet, Caroline Bonmati, Martine Escoffre-Barbe, Laurence Legros, Pascal Turlure, Patrice Chevallier, Fabrice Larosa, Frederic Garban, Oumedaly Reman, Philippe Rousselot, Nathalie Dhédin, André Delannoy, Marina Lafage-Pochitaloff, Marie Christine Béné, Norbert Ifrah, and Hervé Dombret
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia.Design and Methods Sixty patients received either continuous-infusion doxorubicin (12 mg/m2/day) and continuous-infusion vincristine (0.4 mg/day) on days 1–4 or pegylated liposomal doxorubicin (40 mg/m2) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors.Results Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm.Conclusions With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities.
Published: 2011
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16. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia

Author: Jean-Valère Malfuson, Anne Etienne, Pascal Turlure, Thierry de Revel, Xavier Thomas, Nathalie Contentin, Christine Terré, Sophie Rigaudeau, Dominique Bordessoule, Norbert Vey, Claude Gardin, Hervé Dombret, and for the Acute Leukemia French Association (ALFA)
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background There is a need for standardization of treatment decisions in older patients with acute myeloid leukemia. The aim of the present study was to analyze the decisional value of poor risk factors in 416 elderly patients treated in the ALFA-9803 trial in order to derive a decisional index.Design and Methods Standard multivariate analysis was used to identify risk factors for overall survival. Risk factors were then considered as good decision tools if associated with a frequency >10% and a false positive rate
Published: 2008
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17. Complications cardiaques de la greffe de cellules souches hématopoïétiques : recommandations de la SFGM-TC

Author: Imran Ahmad, Laetitia Souchet, Fati Hamzy, Patrice Ceballos, Yohann Desbrosses, Aurélie Ravinet, Pascal Turlure, Alban Villate, Cécile Borel, Hanane Benbarkat, Ibrahim Yakoub-Agha, and Thierry Guillaume
Subjects: Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Published: 2023

18. Nilotinib efficacy and safety as salvage treatment following imatinib intolerance and/or inefficacy in steroid refractory chronic graft-versus-host-disease (SR-cGVHD): a prospective, multicenter, phase II study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Author: Micha Srour, Tamim Alsuliman, Julien Labreuche, Claude-Eric Bulabois, Patrice Chevallier, Etienne Daguindau, Edouard Forcade, Sylvie François, Gaelle Guillerm, Valerie Coiteux, Pascal Turlure, Yves Beguin, Ibrahim Yakoub-Agha, and Leonardo Magro
Subjects: Transplantation, Hematology
Published: 2023

19. Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS

Author: Claire Michel, Marie Robin, Stephane Morisset, Didier Blaise, Johan Maertens, Patrice Chevalier, Cristina Castilla-Llorente, Edouard Forcade, Patrice Ceballos, Ibrahim Yakoug-Agha, Xavier Poire, Martin Carre, Jacques-Olivier Bay, Yves Beguin, Michael Loschi, Anne Huynh, Gaëlle Guillerm, Sylvie François, Jean-Baptiste Mear, Rémy Duléry, Felipe Suarez, Karin Bilger, Jérôme Cornillon, Yves Chalandon, Natacha Maillard, Hélène Labussière-Wallet, Amandine Charbonnier, Pascal Turlure, Ana Berceanu, Sylvain Chantepie, Sébastien Maury, Ali Bazarbachi, Anne-Lise Menard, Stephanie Nguyen-Quoc, Marie-Thérèse Rubio, and Maud D’Aveni
Subjects: Transplantation, Hematology
Abstract: Allogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2–4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32–1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28–1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome.
Published: 2023

20. CPX-351 in higher risk myelodysplastic syndrome and chronic myelomonocytic leukaemia: a multicentre, single-arm, phase 2 study

Author: Pierre Peterlin, Yannick Le Bris, Pascal Turlure, Patrice Chevallier, Audrey Ménard, Marie-Pierre Gourin, Pierre-Yves Dumas, Sylvain Thepot, Ana Berceanu, Sophie Park, Marie-Anne Hospital, Thomas Cluzeau, Simon Bouzy, Jose-Miguel Torregrosa-Diaz, Louis Drevon, Rosa Sapena, Fatiha Chermat, Lionel Ades, Sophie Dimicoli-Salazar, Sylvie Chevret, Marie-Christine Béné, and Pierre Fenaux
Subjects: Hematology
Published: 2023

21. Supplementary Data from Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients

Author: François-Xavier Mahon, Gabriel Etienne, Joëlle Guilhot, Fabrice Larosa, François Guilhot, Emilie Cayssials, Marc G. Berger, Bruno Villemagne, Tawfiq Henni, Patricia Zunic, Bertrand Joly, Henry Jardel, Juliana Martiniuc, Hyacinthe Johnson-Ansah, Pascal Turlure, Jean-Christophe Ianotto, Martine Gardembas, Jixing Liu, Laurence Legros, Agnès Guerci-Bresler, Delphine Rea, Philippe Rousselot, Pascal Lenain, Viviane Dubruille, Bruno Varet, Valérie Coiteux, Françoise Rigal-Huguet, Martine Escoffre-Barbe, Aude Charbonnier, Pascale Cony-Makhoul, Lisa Boureau, Stéphanie Dulucq, and Franck Emmanuel Nicolini
Abstract: Supplemental table 1: Sequence of hydrolysis probes and primers used for the ddPCR.
Published: 2023

22. Data from Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients

Author: François-Xavier Mahon, Gabriel Etienne, Joëlle Guilhot, Fabrice Larosa, François Guilhot, Emilie Cayssials, Marc G. Berger, Bruno Villemagne, Tawfiq Henni, Patricia Zunic, Bertrand Joly, Henry Jardel, Juliana Martiniuc, Hyacinthe Johnson-Ansah, Pascal Turlure, Jean-Christophe Ianotto, Martine Gardembas, Jixing Liu, Laurence Legros, Agnès Guerci-Bresler, Delphine Rea, Philippe Rousselot, Pascal Lenain, Viviane Dubruille, Bruno Varet, Valérie Coiteux, Françoise Rigal-Huguet, Martine Escoffre-Barbe, Aude Charbonnier, Pascale Cony-Makhoul, Lisa Boureau, Stéphanie Dulucq, and Franck Emmanuel Nicolini
Abstract: Purpose:Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation.Patients and Methods:We conducted a prospective national phase II study evaluating the cessation of imatinib after at least 2 years of MR4.5 obtained on imatinib first-line in patients with chronic phase CML.Results:A total of 218 patients with de novo chronic phase CML were involved in the study. The median follow-up after imatinib cessation was 23.5 (1–64) months, 2 patients died from unrelated causes, and 107 experienced a confirmed increase in BCR-ABL1 levels defined as molecular recurrence. The molecular recurrence-free survival was 52% [95% confidence interval (CI), 45%–59%] at 6 months, and 50% (95% CI, 43%–57%) at 24 months. Droplet digital PCR (ddPCR) was used to evaluate more accurately low levels of BCR-ABL1 in 175 of 218 patients at imatinib cessation. To apply positive BCR-ABL1/ABL1 ratios on the international scale (IS), a conversion factor was calculated for ddPCR and the significant cut-off point was established at 0.0023%IS. In a multivariate analysis, the duration of TKI (≥74.8 months) and ddPCR (≥0.0023%IS) were the two identified predictive factors of molecular recurrence, with P = 0.0366 (HR, 0.635; 95% CI, 0.415–0.972] and P = 0.008 (HR, 0.556; 95% CI, 0.360–0.858), respectively.Conclusions:We conclude that the duration of TKI and residual leukemic cell load as determined by ddPCR are key factors for predicting successful treatment-free remission for patients with de novo chronic phase CML.See related commentary by Yan et al., p. 6561
Published: 2023

23. Allogeneic Hematopoietic Stem Cell Transplantation for Adults with Therapy-Related Acute Myeloid Leukemia: a Retrospective Multicentre Study on behalf of the SFGM-TC

Author: Emmanuelle Tavernier, Gaëlle Rey, Elisabeth Daguenet, Paul Bonjean, Raynier Devillier, Nathalie Fegueux, Edouard Forcade, micha sr, patrice chevalier, marie robin, Felipe Suarez, Jean-Baptiste Micol, helene labussiere, Karin Bilger, Etienne Daguindau, Jacques Olivier Bay, Amandine Fayard, Claude-Eric BULABOIS, Stéphanie Nguyen-Quoc, Alexis Genthon, Corentin Orvain, Pascal TURLURE, Michael Loschi, Xavier Poire, Gaella Guillerm, Yves Beguin, Natacha Maillard, jean-baptiste Mear, Emilie Chalayer, and Jerome Cornillon
Abstract: We report the results from a multicentre retrospective study of 220 adult patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) for therapy-related acute myeloid leukemia (t-AML). Median age at t-AML diagnosis was 56 years, with a prior history of haematological (45%) or gynaecological neoplasia (37%). Median time from cytotoxic exposure to t-AML diagnosis was 54.7 months. At transplant, around 20% of patients had measurable residual disease and 3% of patients were not in complete remission. The median follow-up was 21.4 months (Q1-Q3, 5.9–52.8). At 12 months, overall survival (OS), event-free survival (EFS), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS) were 60.7% (95% CI 54.6–67.5), 52.8% (95% CI 46.5–68.4), and 44.1% (95% CI 37.6–51.8), respectively. At 5 years, OS, EFS, and GRFS were 44.1% (95% CI 37.4–52.1), 40.4% (95% CI 33.9–48.1), and 35.3% (95% CI 28.8–43.3), respectively. At last follow-up, 44% of patients were in complete remission (n = 96) and transplant-related mortality accounted for 39% of all deaths (n = 119). Multivariable analysis revealed that uncontrolled t-AML at transplant was associated with lower EFS (HR 1.94, 95% CI 1.0-3.7, p = 0.041). In conclusion, alloHSCT for t-AML shows encouraging results and offers additional opportunity with the emergence of novel pre-graft therapies.
Published: 2023

24. Molecular Response Analysis By High Throughput Sequencing in Higher Risk Myelodysplastic Syndrome (HR-MDS) Treated Intensively with CPX-351

Author: Yannick Le Bris, Simon Bouzy, Audrey Ménard, Pascal Turlure, Patrice Chevallier, Marie-Pierre Gourin, Pierre-Yves Dumas, Sylvain Thepot, Anna Berceanu, Sophie Park, Marie-Anne Hospital, Thomas Cluzeau, Jose-Miguel Torregrosa Diaz, Louis Devron, Rosa Sapena, Fatiha Chermat, Sophie Dimicoli Salazar, Marie C Béné, Pierre Fenaux, and Pierre Peterlin
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

25. Interim Results from Clevo: A Non-Interventional Cohort Study Investigating the Clonal Evolution of FMS-like Tyrosine Kinase 3 (FLT3) Mutations during Disease Progression in Patients with Acute Myeloid Leukemia

Author: Cristina Papayannidis, Blanca Boluda, Jonathan Canaani, Pascal Turlure, Ann De Becker, Anand Tandra, Dina Elsouda, Arnaud Houweling, Anil Upadhyay, Isabelle Wouters, and Paresh Vyas
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

26. On Behalf of the SFGM-TC: Retrospective Comparison of Reduced and Higher Intensity Conditioning for High-Risk Myelodysplastic Syndrome Treated With Allogeneic Stem-Cell Transplantation

Author: Hélène Labussière-Wallet, Stephanie Nguyen-Quoc, Amandine Luc, Thomas Remen, Jacques-Olivier Bay, Edouard Forcade, Rémi Dulery, Marie-Thérèse Rubio, Célestine Simand, Micha Srour, Maud d'Aveni, Ambroise Marçais, Sabine Furst, Arnaud Campidelli, Patrice Ceballos, Etienne Daguindau, Marie Robin, Pascal Turlure, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Eloi, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Dupuytren [CHU Limoges], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Necker - Enfants Malades [AP-HP], and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Transplantation Conditioning, 03 medical and health sciences, 0302 clinical medicine, Conditioning regimen, Risk Factors, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Transplantation, Homologous, Overall survival, Aged, Retrospective Studies, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, medicine.disease, Survival Analysis, Allogeneic stem cell transplantation, 3. Good health, Fludarabine, Transplantation, Covariate adjustment using the propensity, medicine.anatomical_structure, Graft-versus-host disease, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Propensity score matching, Female, Bone marrow, Stem cell, business, Myelodysplastic syndrome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Busulfan, 030215 immunology, medicine.drug
Abstract: International audience; BackgroundAllogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome . We retrospectively compared patient outcomes after allo-HSCT according to the intensity of the conditioning regimen.Patients and MethodsThree conditioning regimens were compared in 427 patients allografted for high-risk myelodysplastic syndrome: reduced-intensity conditioning (RIC), fludarabine (150-160 mg/m2) and busulfan (6.4 mg/kg); sequential FLAMSA-RIC, fludarabine, amsacrine, and aracytine followed by RIC; and myeloablative with reduced toxicity (RTC), fludarabine and busulfan (9.6 mg/kg or 12.8 mg/kg).ResultsThe patients in the 3 conditioning groups were different in regards to the number of treatment lines (P< .001), percentage of blasts in bone marrow (P< .001), and disease status at transplantation (P< .001). No significant differences in outcomes (overall survival, progression-free survival, nonrelapse mortality, relapse incidence, and graft versus host disease relapse-free survival) were observed between the 3 groups. Using propensity score analysis to overcome baseline imbalances, we compared 70 patients receiving FLAMSA-RIC to 260 patients receiving RIC, and compared 83 patients receiving RTC to 252 patients receiving RIC. The only factor influencing overall and progression-free survival was cytogenetic risk at transplantation. After the covariate adjustment using propensity score to reduce baseline imbalances, the only factor influencing overall and progression-free survival was still cytogenetic risk at transplantation.ConclusionOverall survival appears to be similar with the 3 conditioning regimens. The only factor influencing survival is cytogenetic risk at transplantation, suggesting that new promising drugs in the conditioning and/or early interventions after transplantation are needed to improve outcomes in these patients.
Published: 2022

27. Post-transplant cyclophosphamide in acute leukemia patients receiving more than 5/10 HLA-mismatched allogeneic hematopoietic cell transplantation from related donors: A study on behalf of the ALWP of the EBMT

Author: Michele Wieczorek, Myriam Labopin, Luca Castagna, Eolia Brissot, Gerard Socié, Anna Maria Raiola, Emanuele Angelucci, Arancha Bermúdez Rodríguez, Ibrahim Yakoub‐Agha, Mahmoud Aljurf, Charles Crawley, Jean Baptiste Mear, Maurizio Musso, Renato Fanin, Daniele Avenoso, Pascal Turlure, Cristina Tecchio, Jaime Sanz, Fabio Ciceri, Arnon Nagler, and Mohamad Mohty
Subjects: Hematology
Published: 2023

28. Machine learning identifies the independent role of dysplasia in the prediction of response to chemotherapy in AML

Author: Nicolas Freynet, Hervé Dombret, Daniel Lusina, Emmanuel Benayoun, Xavier Thomas, Estelle Guérin, Raphael Itzykson, Pascal Turlure, Claude Preudhomme, Laurène Fenwarth, Christine Terré, Aline Renneville, Elise Fournier, Thomas Boyer, Bouchra Badaoui, Isabel Garcia, Cécile Pautas, Thomas Cluzeau, Claude Gardin, Orianne Wagner-Ballon, Matthieu Duchmann, Juliette Lambert, Pierre Fenaux, Meyling Cheok, and Bruno Quesnel
Subjects: Adult, Male, Cancer Research, NPM1, medicine.medical_treatment, Antineoplastic Agents, Machine learning, computer.software_genre, Logistic regression, Machine Learning, medicine, Humans, Complete response, Aged, Chromosome 7 (human), Chemotherapy, business.industry, Myeloid leukemia, Hematology, Middle Aged, Prognosis, medicine.disease, Clinical trial, Leukemia, Myeloid, Acute, Treatment Outcome, Oncology, Dysplasia, Cytogenetic Analysis, Female, Artificial intelligence, business, Megakaryocytes, computer
Abstract: The independent prognostic impact of specific dysplastic features in acute myeloid leukemia (AML) remains controversial and may vary between genomic subtypes. We apply a machine learning framework to dissect the relative contribution of centrally reviewed dysplastic features and oncogenetics in 190 patients with de novo AML treated in ALFA clinical trials. One hundred and thirty-five (71%) patients achieved complete response after the first induction course (CR). Dysgranulopoiesis, dyserythropoiesis and dysmegakaryopoiesis were assessable in 84%, 83% and 63% patients, respectively. Multi-lineage dysplasia was present in 27% of assessable patients. Micromegakaryocytes (q = 0.01), hypolobulated megakaryocytes (q = 0.08) and hyposegmented granulocytes (q = 0.08) were associated with higher ELN-2017 risk. Using a supervised learning algorithm, the relative importance of morphological variables (34%) for the prediction of CR was higher than demographic (5%), clinical (2%), cytogenetic (25%), molecular (29%), and treatment (5%) variables. Though dysplasias had limited predictive impact on survival, a multivariate logistic regression identified the presence of hypolobulated megakaryocytes (p = 0.014) and micromegakaryocytes (p = 0.035) as predicting lower CR rates, independently of monosomy 7 (p = 0.013), TP53 (p = 0.004), and NPM1 mutations (p = 0.025). Assessment of these specific dysmegakarypoiesis traits, for which we identify a transcriptomic signature, may thus guide treatment allocation in AML.
Published: 2021

29. In Adults with Ph-Negative Acute Lymphoblastic Leukemia (ALL), Age-Adapted Chemotherapy Intensity and MRD-Driven Transplant Indication Significantly Reduces Treatment-Related Mortality (TRM) and Improves Overall Survival - Results from the Graall-2014 Trial

Author: Nicolas Boissel, Francoise Huguet, Thibaut Leguay, Hunault-Berger Mathilde, Carlos Graux, Yves Chalandon, Eric Delabesse, Yosr Hicheri, Patrice Chevallier, Marie Balsat, Cedric Pastoret, Martine Escoffre-Barbe, Florence Pasquier, Jean-Pierre Marolleau, Anne Thiebaut-Bertrand, Anne Huynh, Nathalie Dhedin, Emilie Lemasle, Caroline Bonmati, Sébastien Maury, Gaëlle Guillerm, Anna Berceanu, Urs Schanz, Thomas Cluzeau, Pascal Turlure, Philippe Rousselot, Bernard J.M. De Prijck, Nathalie Grardel, Marie C Bene, Marine Lafage, Norbert Ifrah, Veronique Lheritier, Vahid Asnafi, Emmanuelle Clappier, Herve Dombret, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU UCL Namur, Hôpitaux Universitaires de Genève (HUG), 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], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique moléculaire de la transformation hématopoïétique (Dynamo), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), CHU Amiens-Picardie, Centre Hospitalier Universitaire [Grenoble] (CHU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University hospital of Zurich [Zurich], Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), CHU Limoges, Centre Hospitalier de Versailles André Mignot (CHV), CHU Sart Tilman [Liege, Belgium], CHU Lille, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), CHU d'Angers [Département Urgences], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Coordination du Groupe GRAALL [CH Lyon-Sud], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], 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), and DESSAIVRE, Louise
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background During the 2005-2014 period, the GRAALL conducted the GRAALL-2005 trial in patients (pts) with Philadelphia chromosome (Ph)-negative ALL aged 18-59y. In this trial, all pts received a pediatric-inspired chemotherapy, whatever their age. Post-hoc analysis revealed an unacceptable TRM in pts aged 45-59y (Huguet et al. J Clin Oncol 2018; 36:2514-23). Allogeneic hematopoietic stem cell transplantation (HSCT) was offered in first complete remission (CR) to most CR pts, defined at high-risk (HR) by at least one baseline clinical or biological HR factor (CNS involvement, complex karyotype [≥5 abns.], low hypodiploidy/near triploidy, poor early blast clearance, late CR, as well as WBC ≥ 30x109/L, lack of CD10 expression, KMT2A rearrangement or TCF3::PBX1 fusion for B-cell precursor [BCP] ALL). Minimal residual disease (MRD) response was not considered for HSCT indication at that time.In the next GRAALL-2014 trial conducted in a similar population, we introduced two major changes in the treatment strategy. First, chemotherapy intensity (steroids, anthracycline and L-asparaginase) was reduced in pts aged 45-59y to decrease excessive TRM. Secondly, the indication for HSCT was modified, relying on IG/TR MRD response only (post-induction MRD ≥10-3 and/or post-consolidation MRD ≥10-4) while not on any former baseline HR criterion. Here, we compare the outcomes of the two trials, focusing on the impact of these two major evolutions.Patients & Methods A total of 743 pts treated in the GRAALL-2014 trial between 2015 and 2020 were compared to the 787 pts from the historical GRAALL-2005 trial, in terms of CR and induction death rates, rate of HSCT in CR1, cumulative incidence of TRM (CITRM) and relapse (CIR), relapse-free (RFS) and overall (OS) survival. It should be noted that two nested Phase 2 trials were introduced by amendment during the GRAALL-2014 course (in 2017 and 2018, respectively), aiming to evaluate post-remission addition of nelarabine and blinatumomab in 87 T-ALL and 94 BCP-ALL selected pts, respectively.Results Main patient characteristics, including age, gender, BCP/T-ALL, WBC, and historical baseline HR features, did not significantly differ between the two trial cohorts, even if CNS disease at diagnosis was more frequent in the 2014 cohort (12 vs 7%, p= 0.001).Outcome comparisons are shown in Table 1. Overall, the induction death rate was significantly reduced in the GRAALL-2014 (3 vs 6%, p= 0.005). As expected, this was only observed in pts aged 44-59y (3 vs 11%, p= 0.001), in whom dose-intensity reduction also translated into a higher need for second induction course (9 vs 5%, p= 0.05) eventually resulting in a higher CR rate (92 vs 86%, p= 0.05). Due to the newly introduced MRD-based stratification, the rate of pts with HSCT indication was markedly reduced (30 vs 65%, p
Published: 2022

30. Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO

Author: Pierre-Yves Dumas, Emmanuel Raffoux, Emilie Bérard, Sarah Bertoli, Marie-Anne Hospital, Maël Heiblig, Yohann Desbrosses, Caroline Bonmati, Cécile Pautas, Juliette Lambert, Corentin Orvain, Anne Banos, Florence Pasquier, Pierre Peterlin, Tony Marchand, Madalina Uzunov, Jamilé Frayfer, Pascal Turlure, Thomas Cluzeau, Eric Jourdan, Chantal Himberlin, Emmanuelle Tavernier, Alban Villate, Stephanie Haiat, Marie-Lorraine Chretien, Martin Carre, Sylvain Chantepie, Ioana Vaida, Mathieu Wemeau, Safia Chebrek, Gaelle Guillerm, Romain Guièze, Houria Debarri, Eve Gehlkopf, Kamel Laribi, Ambroise Marcais, Alberto Santagostino, Marie-Christine Béné, Ariane Mineur, Arnaud Pigneux, Hervé Dombret, and Christian Récher
Subjects: Cancer Research, Oncology, Hematology
Abstract: The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.
Published: 2022

31. Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf SFGM-TC and FIM groups

Author: Claude Eric Bulabois, Nicole Raus, Anne Huynh, Valerie Rolland, Marie Hélène Schlageter, Brigitte Dupriez, Jean-Jacques Kiladjian, Edouard Forcade, David Michonneau, Stéphanie N. Guyen, Alban Villate, Fiorenza Barraco, Raphaël Porcher, Felipe Suarez, Bruno Cassinat, Amandine Charbonnier, Françoise Boyer, Jacques-Olivier Bay, Gérard Socié, Jérôme Cornillon, Sylvain Chantepie, Ibrahim Yakoub-Agha, Laure Vincent, Pascal Turlure, Marie Robin, Corentin Orvain, and Marie Y Detrait
Subjects: Ruxolitinib, medicine.medical_specialty, Transplantation Conditioning, Graft vs Host Disease, Diseases, Article, Phase II trials, 03 medical and health sciences, 0302 clinical medicine, Unrelated Donor, Internal medicine, Nitriles, Humans, Medicine, In patient, Cumulative incidence, Prospective Studies, Myelofibrosis, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, Haematopoiesis, Pyrimidines, Primary Myelofibrosis, International Prognostic Scoring System, 030220 oncology & carcinogenesis, Pyrazoles, Unrelated Donors, business, 030215 immunology, medicine.drug
Abstract: This multicenter prospective phase 2 trial analyzed disease-free survival (DFS) in myelofibrosis patients receiving ruxolitinib for 6 months before transplantation. Seventy-six patients were recruited. Age-adjusted dynamic international prognostic scoring system was intermediate-1, intermediate-2, and high in 27 (36%), 31 (41%), and 18 (24%) patients. All patients received ruxolitinib from inclusion to conditioning regimen (fludarabine-melphalan) or to progression. A donor was found in 64 patients: 18 HLA-matched sibling donor (MSD), 32 HLA-matched unrelated (UD10/10), and 14 HLA mismatched unrelated donor (UD9/10. Among 64 patients with a donor, 20 (31%) achieved a partial response before transplantation and 59 (92%) could be transplanted after ruxolitinib therapy (18/18 MSD, 30/21 UD10/10, 11/34 UD9/10), of whom 19 (32%) were splenectomized. Overall survival from inclusion was 68% at 12 months. One-year DFS after transplantation was 55%: 83%, 40%, and 34% after MSD, UD10/10 or UD9/10, respectively. Cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) was 66% and non-relapse-mortality was 42% at 12 months. Short course of ruxolitinib before transplantation is followed by a high rate of transplantation. With the platform used in this protocol, outcome was much better in patients transplanted with HLA-matched sibling donor as compared to unrelated donor.
Published: 2021

32. Medication non‐adherence after allogeneic hematopoietic cell transplantation in adult and pediatric recipients: a cross sectional study conducted by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Author: Claire Vignaux, Dominique Plantaz, Claude-Eric Bulabois, Eva de Berranger, Bertrand Décaudin, Bruno Lioure, Yosr Hicheri, Jean-Henri Bourhis, Virginie Gandemer, Patrice Ceballos, Nathalie Contentin, Fanny Rialland, Anne Sirvent, Pascal Turlure, Leonardo Magro, Bénédicte Bruno, Stéphanie Belaiche, Nathalie Fegueux, Anne Huynh, Claire Galambrun, Valérie Coiteux, Pascal Odou, Jacques-Olivier Bay, Laure Vincent, Alexandre Caron, Stephane Vigouroux, Ibrahim Yakoub-Agha, Dominique Farge, Sophie Taque, Nicolas Depas, Natacha Maillard, and Jérôme Cornillon
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Cross-sectional study, medicine.medical_treatment, Population, Acyclovir, 030226 pharmacology & pharmacy, Medication Adherence, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Belgium, Surveys and Questionnaires, Internal medicine, medicine, Humans, Pharmacology (medical), Child, education, Pharmacology, education.field_of_study, Univariate analysis, Hematopoietic cell, business.industry, Hematopoietic Stem Cell Transplantation, Immunosuppression, Middle Aged, Transplantation, Cross-Sectional Studies, Algeria, Cyclosporine, Female, business, 030217 neurology & neurosurgery
Abstract: Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA.
Published: 2021

33. Prise en charge des complications ophtalmologiques de l’allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Cécile Borel, Patrice Ceballos, Thierry Guillaume, Fati Hamzy, Yohann Desbrosses, Ibrahim Yakoub-Agha, Alban Villate, Imran Ahmad, Aurélie Ravinet, Pascal Turlure, and Laetitia Souchet
Subjects: 0301 basic medicine, 03 medical and health sciences, Cancer Research, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Abstract: Resume Introduction L’allogreffe de cellules souches hematopoietiques est la seule therapeutique curative pour de nombreuses hemopathies. Ce traitement peut donner lieu a des complications, notamment ophtalmologiques. Methodes Nous avons realise une revue de la litterature et nous avons etabli des recommandations accessibles et pratiques pour les hematologues et les ophtalmologues. Resultats Le suivi ophtalmologique doit etre systematique chez les patients ayant eu une allogreffe, par l’interrogatoire de l’hematologue et l’examen de l’ophtalmologue. Les complications liees a la reaction du greffon contre l’hote (GVHD) et non liees a la GVHD sont listees, ainsi que les differentes therapeutiques. Discussion Le depistage et le traitement des complications ophtalmologiques de l’allogreffe necessitent une collaboration etroite entre hematologues et ophtalmologues. La prise en charge par des soignants formes dans ce type de pathologie est recommandee.
Published: 2020

34. Prognostic Impact of Monoallelic Versus Biallelic TP53 Alterations in Intensively-Treated Adults AML Patients: A Retrospective Study from the ALFA Group

Author: Laurène Fenwarth, Loïc Vasseur, Nicolas Duployez, Claude Gardin, Christine Terré, Juliette Lambert, Stéphane de Botton, Karine Celli-Lebras, Pascal Turlure, Thomas Cluzeau, Thorsten Braun, Xavier Thomas, Christian Recher, Sylvain Chantepie, Cécile Pautas, Hervé Dombret, Claude Preudhomme, and Raphael Itzykson
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

35. Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091)

Author: Johan, Maertens, Tom, Lodewyck, J, Peter Donnelly, Sylvain, Chantepie, Christine, Robin, Nicole, Blijlevens, Pascal, Turlure, Dominik, Selleslag, Frédéric, Baron, Mickael, Aoun, Werner J, Heinz, Hartmut, Bertz, Zdeněk, Ráčil, Bernard, Vandercam, Lubos, Drgona, Valerie, Coiteux, Cristina Castilla, Llorente, Cornelia, Schaefer-Prokop, Marianne, Paesmans, Lieveke, Ameye, Liv, Meert, Kin Jip, Cheung, Deborah A, Hepler, Jürgen, Loeffler, Rosemary, Barnes, Oscar, Marchetti, Paul, Verweij, Frederic, Lamoth, Pierre Yves, Bochud, Michael, Schwarzinger, and Catherine, Cordonnier
Abstract: Empiric antifungal therapy is considered the standard-of-care for high-risk neutropenic patients with persistent fever. The impact of a pre-emptive, diagnostic-driven approach based on galactomannan (GM) screening and chest CT-scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown.Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (Arm A) or pre-emptively (Arm B). All patients received fluconazole 400 mg daily as prophylaxis. The primary endpoint of this non-inferiority study was overall survival (OS) 42 days after randomization.Of 556 patients recruited, 549 were eligible: 275 in Arm A, 274 in Arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy and 93% of them were in first induction phase. At day 42, the OS was not inferior in Arm B (96.7%; 95% confidence interval (CI), 93.8 - 98.3%) when compared to Arm A (93.1%; 95% CI, 89.3 - 95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95%CI, 4.5-10.8%) in Arm B versus 6.6% (95%CI, 3.6-9.5%) in Arm A, respectively. The rate of patients receiving caspofungin was significantly lower in Arm B (27%) than in Arm A (63%) (p 0.001).The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs.
Published: 2022

36. Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC

Author: Natacha Maillard, Sylvain Chantepie, Tony Marchand, Myriam Labopin, Régis Peffault de Latour, Ibrahim Yakoub-Agha, Karin Bilger, Didier Blaise, Pascal Turlure, Marie C. Béné, Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Mohamad Mohty, Marie-Thérèse Rubio, Patrice Chevallier, Stéphanie Nguyen, Edouard Forcade, Patrice Ceballos, Anne Huynh, Amandine Charbonnier, Ambroise Marçais, Amandine Le Bourgeois, Thierry Guillaume, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), CHU Amiens-Picardie, CHU Limoges, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], 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), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Toulouse [Toulouse], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Transplantation Conditioning, Adolescent, Cyclophosphamide, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Clofarabine, education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Chemotherapy, education.field_of_study, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, General Medicine, Middle Aged, Allografts, 3. Good health, Survival Rate, Transplantation, Leukemia, Myeloid, Acute, Regimen, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Busulfan, 030215 immunology, medicine.drug
Abstract: Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.
Published: 2020

37. Population pharmacokinetics and Bayesian estimators for intravenous mycophenolate mofetil in haematopoietic stem cell transplant patients

Author: Jean-Baptiste Woillard, Jean Debord, Stephane Girault, Caroline Monchaud, Pierre Marquet, Julien Vaidie, Marc Labriffe, and Pascal Turlure
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Population, Urology, Hematopoietic stem cell transplantation, Mycophenolate, 030226 pharmacology & pharmacy, Mycophenolic acid, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Dosing, education, Pharmacology, education.field_of_study, business.industry, Hematopoietic Stem Cell Transplantation, Area under the curve, Bayes Theorem, Original Articles, Mycophenolic Acid, Transplantation, Area Under Curve, Female, business, Immunosuppressive Agents, medicine.drug
Abstract: Aims Intravenous mycophenolate mofetil (IV MMF), a prodrug of mycophenolic acid (MPA), is used during nonmyeloablative and reduced-intensity conditioning haematopoetic stem cell transplantation (HCT) to improve engraftment and reduce graft-versus-host disease. The aims of this study were to develop population pharmacokinetic models and Bayesian estimators based on limited sampling strategies to allow for individual dose adjustment of intravenous mycophenolate mofetil administered by infusion in haematopoietic stem cell transplant patients. Methods Sixty-three MPA concentration-time profiles (median [min-max] = 6 [4-7] samples) were collected from 34 HCT recipients transplanted for 14 (1-45) days and administered IV MMF every 8 hours, concomitantly with cyclosporine. The database was split into development (75%) and validation (25%) datasets. Pharmacokinetic models characterized by a single compartment with first-order elimination, combined with two gamma distributions to describe the transformation of MMF into mycophenolic acid, were developed using in parallel nonparametric (Pmetrics) and parametric (ITSIM) approaches. The performances of the models and the derived Bayesian estimators were evaluated in the validation set. Results The best limited sampling strategy led to a bias (min, max), root mean square error between observed and modeled interdose areas under the curve in the validation dataset of -11.72% (-31.08%, 5.00%), 14.9% for ITSIM and -2.21% (-23.40%, 30.01%), 12.4% for Pmetrics with three samples collected at 0.33, 2 and 3 hours post dosing. Conclusion Population pharmacokinetic models and Bayesian estimators for IV MMF in HCT have been developed and are now available online (https://pharmaco.chu-limoges.fr) for individual dose adjustment based on the interdose area under the curve.
Published: 2020

38. Insuffisance rénale et allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Eva de Berranger, Selami Kocak Toprak, Ibrahim Yakoub-Agha, Thierry Guillaume, Pascal Turlure, Sylvain Thepot, Marie Y. Detrait, Anne-Lise Ménard, Remy Dulery, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université d'Angers (UA), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Ankara Üniversitesi, CHU Lille, Centre hospitalier universitaire de Nantes (CHU Nantes), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bone marrow transplantation, [SDV]Life Sciences [q-bio], Renal complications, urologic and male genital diseases, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Renal Failures, Medicine, Radiology, Nuclear Medicine and imaging, Allogreffe de cellules souches hématopoïétiques, Gynecology, business.industry, Hematology, General Medicine, 3. Good health, Complications rénales, [SDV] Life Sciences [q-bio], Transplantation, surgical procedures, operative, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Allogeneic hsct, Allogeneic hematopoietic stem cell transplantation, business
Abstract: International audience; Acute and chronic renal failures are very common after allogeneic HSCT. These complications have a real impact on mortality and morbidity of transplant recipients. Within the framework of the ninth workshops of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held in Lille in September 2018, various causes and mechanisms of renal failure, diagnostic work-up, treatment and recommendations to limit renal failure after transplantation are reviewed. Recommendations to adjust medications to avoid renal failure are also proposed in this article.
Published: 2020

39. Complications hépatobiliaires dans le contexte de l’allogreffe de cellules hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Ibrahim Yakoub-Agha, Selami Kocak Toprak, Eva de Berranger, Pascal Turlure, Remy Dulery, Sylvain Thepot, Anne-Lise Ménard, Thierry Guillaume, Marie Y. Detrait, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université d'Angers (UA), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Ankara Üniversitesi, CHU Lille, Centre hospitalier universitaire de Nantes (CHU Nantes), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Hematology, General Medicine, Allogeneic stem cell transplantation, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, surgical procedures, operative, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Hepatobiliary complications, Radiology, Nuclear Medicine and imaging, Complications hépatobiliaires, Allogreffe de cellules souches hématopoïétiques
Abstract: Resume Les complications stomatologiques de l’allogreffe de cellules souches hematopoietiques (CSH) sont frequentes et tres inconfortables pour les patients. La reaction du greffon contre l’hote represente la principale complication. Les infections, les troubles du gout et les risques carcinologiques constituent les autres effets secondaires de la procedure. Differents traitements locaux sont utilises mais restent imparfaits. Dans le cadre de la dixieme edition des ateliers d’harmonisation des pratiques en allogreffe, organises par la Societe francophone de greffe de moelle et de therapie cellulaire (SFGM-TC) a Lille, en septembre 2019, la demarche diagnostique et les traitements des complications orales apres allogreffe de CSH ont ete revus apres analyse des resultats des etudes publiees.
Published: 2020

40. Sexual function of adult long-term survivors and their partners after allogeneic hematopoietic cell transplantation in Europe (S-FAST):a study from the Transplant Complications Working Party and Nurses Group of the EBMT

Author: Lars Klingen Gjærde, Corien Eeltink, Jacqui Stringer, Jarl Mooyaart, Paul Bosman, Michelle Kenyon, Sarah Liptrott, Diana M. Greenfield, Andrea Linke, Pascal Turlure, Stefano Botti, Dzenana Dzaferagic, Simona Sica, Lorna Welsh, Annika Kisch, Zinaida Perić, Hélène Schoemans, John Murray, and Hematology
Subjects: Transplantation, Settore MED/15 - MALATTIE DEL SANGUE, Hematology, Sexual function of adult long-term survivors and their partners after allogeneic hematopoietic cell transplantation in Europe
Abstract: Sexual dysfunction after allogeneic hematopoietic cell transplantation (allo-HCT) is a common long-term complication. We conducted a European multicenter cross-sectional study of adult allo-HCT recipients who had survived >2 years and their partners to investigate sexual functioning after HCT and to evaluate whether discussion about sexual functioning between the transplant team and the survivor and partner was perceived to have taken place. In total, 136 survivors (77 males, 59 females) and 81 partners (34 males, 47 females) participated. Median age was 56 and 54 years in male and female survivors, respectively. Forty-seven percent of male and 65% of female survivors and 57% of male and 59% of female partners reported clinically relevant sexual problems. Sixty-two percent of survivors and 79% of partners reported that sexual functioning had not been discussed with them during transplant. Standardized sexual functioning scores were correlated with self-reported health status in survivors (rho = 0.24, p = 0.009). The high prevalence of sexual dysfunction warrants additional studies focusing on the impact of changes in sexuality for patients as well as their partners. Future studies should also investigate which methods that are effective in preventing or treating sexual problems after allo-HCT.
Published: 2022

41. [Cardiac complications following allogeneic hematopoietic stem cell transplantation: Recommendations of the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC)]

Author: Imran, Ahmad, Laetitia, Souchet, Fati, Hamzy, Patrice, Ceballos, Yohann, Desbrosses, Aurélie, Ravinet, Pascal, Turlure, Alban, Villate, Cécile, Borel, Hanane, Benbarkat, Ibrahim, Yakoub-Agha, and Thierry, Guillaume
Abstract: Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) can lead to early cardiac complications as well as late sequelae. A cardiac evaluation is essential in the pre-transplant assessment given the patient's comorbidities and previous chemotherapy treatments received. Various thresholds of cardiac function are recommended as eligibility criteria. The rise of haplo-identical transplantation with the use of post-transplant high-dose cyclophosphamide (PT-Cy) as a prophylaxis against graft-versus-host disease (GVHD) is accompanied by a resurgence of cardiological concerns. Arrhythmias are also a concern and the list of drugs implicated in this complication is growing. The rare occurrence of cardiac GVHD has been reported, although the entity is not well defined. Finally, although long-term follow-up recommendations exist, they are not accompanied by specific targets for cardiovascular risk factors, the presence of which is nevertheless increased after HSCT. In the framework of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) practice harmonization workshops held in Lille in September 2019, the prophylaxis, the diagnostic approach and the treatments of cardiac complication following HSCT were reviewed after analysis of published studies.
Published: 2021

42. Characteristics and clinical outcomes of SARS-CoV-2 infection in adult patients with acute leukemia in France

Author: Pierre-Yves, Dumas, Sarah, Bertoli, Caroline, Bonmati, Martin, Carre, Juliette, Lambert, Mario, Ojeda-Uribe, Sylvain, Chantepie, Franciane, Paul, Eric, Jourdan, Stéphanie, Haiat, Emmanuelle, Tavernier, Pierre, Peterlin, Jean-Pierre, Marolleau, Kamel, Laribi, Corentin, Orvain, Quentin, Cabrera, Pascal, Turlure, Stéphane, Girault, Marie, Balsat, Marc, Bernard, Marie-Christine, Bene, Arnaud, Pigneux, Hervé, Dombret, and Christian, Récher
Subjects: Adult, Leukemia, Myeloid, Acute, Cancer Research, Oncology, SARS-CoV-2, Acute Disease, COVID-19, Humans, France, Hematology
Published: 2022

43. Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial

Author: null Olivier Tournilhac, null Magali Le Garff-Tavernier, null Stéphanie Nguyen Quoc, null Edouard Forcade, null Patrice Chevallier, null Faezeh Legrand-Izadifar, null Gandhi Laurent Damaj, null David Michonneau, null Cécile Tomowiak, null Cécile Borel, null Corentin Orvain, null Pascal Turlure, null Rabah Redjou, null Gaëlle Guillerm, null Laure Vincent, null Celestine Simand, null Richard Lemal, null Claire Quiney, null Patricia Combes, null Bruno Pereira, null Laure Calvet, null Aurélie Cabrespine, null Jacques-Olivier Bay, null Véronique Leblond, null Nathalie Dhédin, French Innovative Leukemia Organization (FILO), Société Francophone de Greffe De Moelle et de Thérapie Cellulaire (SFGM-TC), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)
Subjects: Oncology, medicine.medical_specialty, Neoplasm, Residual, Transplantation Conditioning, Chronic lymphocytic leukemia, medicine.medical_treatment, Phases of clinical research, Graft vs Host Disease, Hematopoietic stem cell transplantation, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Cumulative incidence, Prospective Studies, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Donor Lymphocytes, Minimal residual disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Regimen, Graft-versus-host disease, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing chronic lymphocytic leukemia (CLL). Minimal residual disease (MRD) assessment at 12 months (M12) post-HSCT is predictive of relapse. This phase II study aimed to achieve M12 MRD negativity (MRDneg) using an MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed in case of failure by donor lymphocytes infusions. Patients had high-risk CLL according to the 2006 European Society for Blood and Marrow Transplantation consensus, in complete or partial response with lymphadenopathy
Published: 2021

44. Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients

Author: Tawfiq Henni, Aude Charbonnier, Martine Escoffre-Barbe, Pascal Turlure, Franck E. Nicolini, Emilie Cayssials, Marc G. Berger, Agnès Guerci-Bresler, Pascale Cony-Makhoul, Juliana Martiniuc, François Guilhot, Jixing Liu, Joelle Guilhot, Gabriel Etienne, Jean-Christophe Ianotto, Patricia Zunic, Bruno Villemagne, Fabrice Larosa, Viviane Dubruille, Lisa Boureau, Henry Jardel, Philippe Rousselot, Laurence Legros, Françoise Rigal-Huguet, Stéphanie Dulucq, Bertrand Joly, Delphine Rea, Martine Gardembas, Francois-Xavier Mahon, Pascal Lenain, Hyacinthe Johnson-Ansah, Valérie Coiteux, Bruno Varet, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Neoplasm, Residual, medicine.drug_class, Fusion Proteins, bcr-abl, Phases of clinical research, Drug Administration Schedule, Article, Tyrosine-kinase inhibitor, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, Survival analysis, Aged, Gene Expression Regulation, Leukemic, business.industry, Remission Induction, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Imatinib, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Confidence interval, 3. Good health, Discontinuation, Treatment Outcome, 030220 oncology & carcinogenesis, Leukemia, Myeloid, Chronic-Phase, Imatinib Mesylate, Female, Neoplasm Recurrence, Local, business, 030215 immunology, medicine.drug, Chronic myelogenous leukemia
Abstract: Purpose: Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation. Patients and Methods: We conducted a prospective national phase II study evaluating the cessation of imatinib after at least 2 years of MR4.5 obtained on imatinib first-line in patients with chronic phase CML. Results: A total of 218 patients with de novo chronic phase CML were involved in the study. The median follow-up after imatinib cessation was 23.5 (1–64) months, 2 patients died from unrelated causes, and 107 experienced a confirmed increase in BCR-ABL1 levels defined as molecular recurrence. The molecular recurrence-free survival was 52% [95% confidence interval (CI), 45%–59%] at 6 months, and 50% (95% CI, 43%–57%) at 24 months. Droplet digital PCR (ddPCR) was used to evaluate more accurately low levels of BCR-ABL1 in 175 of 218 patients at imatinib cessation. To apply positive BCR-ABL1/ABL1 ratios on the international scale (IS), a conversion factor was calculated for ddPCR and the significant cut-off point was established at 0.0023%IS. In a multivariate analysis, the duration of TKI (≥74.8 months) and ddPCR (≥0.0023%IS) were the two identified predictive factors of molecular recurrence, with P = 0.0366 (HR, 0.635; 95% CI, 0.415–0.972] and P = 0.008 (HR, 0.556; 95% CI, 0.360–0.858), respectively. Conclusions: We conclude that the duration of TKI and residual leukemic cell load as determined by ddPCR are key factors for predicting successful treatment-free remission for patients with de novo chronic phase CML. See related commentary by Yan et al., p. 6561
Published: 2019

45. EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL)

Author: Liisa Volin, Wieslaw Wiktor-Jedrzejczak, Donald Bunjes, Leopold Sellner, Per Ljungman, M Rovira, Gerald Wulf, Maija Itälä-Remes, Yener Koc, Michael Potter, Jennifer Hoek, Tobias Gedde-Dahl, Robert Foa, Arnon Nagler, Amit Patel, Jürgen Finke, Jan J. Cornelissen, Patrice Chevallier, A. van Biezen, Nicolaus Kröger, Pascal Turlure, M. J. de Groot, Johannes Schetelig, Péter Reményi, Diderik Jan Eikema, Peter Dreger, Sonja Martin, E. Deconinck, Arne Brecht, Joanna Drozd-Sokołowska, Matthew Collin, Simona Iacobelli, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Helsinki University Hospital Area, and Hematology
Subjects: Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Adolescent, medicine.medical_treatment, 3122 Cancers, Adult, Aged, Allografts, Disease-Free Survival, Humans, Middle Aged, Prospective Studies, Survival Rate, Hematopoietic Stem Cell Transplantation, Leukemia, Prolymphocytic, T-Cell, Registries, Whole-Body Irradiation, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective cohort study, Survival rate, Aged, Transplantation, Univariate analysis, Leukemia, ALEMTUZUMAB, business.industry, Prolymphocytic, Hematology, Total body irradiation, T-Cell, Settore MED/15, 3. Good health, Settore MED/01, 030220 oncology & carcinogenesis, Alemtuzumab, Female, FLUDARABINE, business, 030215 immunology, medicine.drug
Abstract: Preliminary data suggest that allogeneic stem cell transplantation (allo-SCT) may be effective in T-prolymphocytic leukemia (T-PLL). The purpose of the present observational study was to assess the outcome of allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL. Patients were consecutively registered with the EBMT at the time of transplantation and followed by routine EBMT monitoring but with an extended dataset. Between 2007 and 2012, 37 evaluable patients (median age 56 years) were accrued. Pre-treatment contained alemtuzumab in 95% of patients. Sixty-two percent were in complete remission (CR) at the time of allo-SCT. Conditioning contained total body irradiation with 6 Gy or more (TBI6) in 30% of patients. With a median follow-up of 50 months, the 4-year non-relapse mortality, relapse incidence, progression-free (PFS) and overall survival were 32, 38, 30 and 42%, respectively. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM. This study confirms for the first time prospectively that allo-SCT can provide long-term disease control in a sizable albeit limited proportion of patients with T-PLL.
Published: 2019

46. Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Author: Régis Peffault de Latour, Pierre-Simon Rohrlich, Anne Sirvent, Ana Berceanu, Matthieu Resche-Rigon, Charlotte Jubert, Didier Blaise, Bénédicte Neven, Marie-Thérèse Rubio, Patrice Chevallier, Stéphanie Nguyen, Jacques-Olivier Bay, Claude-Eric Bulabois, Noel Milpied, Mohamad Mohty, Gérard Socié, Pascal Turlure, Pedro Henrique Prata, Amandine Charbonnier, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Adult, Male, medicine.medical_specialty, Cyclophosphamide, Graft vs Host Disease, Context (language use), Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Cumulative incidence, ComputingMilieux_MISCELLANEOUS, Bone Marrow Transplantation, Transplantation, Neutrophil Engraftment, business.industry, Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Allografts, Confidence interval, 3. Good health, Fludarabine, Surgery, Survival Rate, Regimen, surgical procedures, operative, Child, Preschool, 030220 oncology & carcinogenesis, Acute Disease, Female, business, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract: Prognosis of patients with graft failure is dismal, and retransplantation is the sole option for long-term survival. To address the interest of haploidentical transplantation as a salvage option in this context, we analyzed data from 24 patients with graft failure or loss retransplanted with a haploidentical donor who received post-transplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis (GVHD). Fludarabine-based reduced-intensity conditioning was used in 23 patients and the Baltimore regimen in 14 patients. The median delay between previous and salvage transplantation for graft failure was 63 days (range, 39 to 98). In addition to PTCy, all patients received cyclosporine, and 22 patients also received mycophenolate mofetil for GVHD prophylaxis. With a median follow-up of 353 days (range, 16 to 2010), 1-year overall survival (OS) was 56% (95% confidence interval, 38% to 81%). Transplant complications accounted for 80% of deaths. The cumulative incidence of neutrophil engraftment at day +30 was 79%. Cumulative incidence of grades II to IV acute GVHD at day 100 was 14%, and 1-year cumulative incidence of chronic GVHD was 31%. One-year cumulative incidence of relapse was 13%. Stem cell source did not impact on engraftment, GVHD, relapse, or OS. Salvage haploidentical transplant with PTCy for rescuing graft failure patients leads to an acceptable 1-year OS and might be a valid option in this poor situation.
Published: 2019

47. Comparison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft-versus-host-disease prophylaxis for matched unrelated donor transplant in acute myeloid leukemia. A study from the ALWP of the EBMT

Author: Bruno Lioure, Johan Maertens, Gérard Socié, Eric Deconinck, Annalisa Paviglianiti, Didier Blaise, Igor Wolfgang Blau, Claude Eric Bulabois, Mohamad Mohty, Anne Huynh, Pascal Turlure, Myriam Labopin, Arnon Nagler, Patrice Chevallier, Gaelle Guillerm, Patrice Ceballos, Edouard Forcade, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-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), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), Hôpital de Hautepierre [Strasbourg], Hôpital Lapeyronie [Montpellier] (CHU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), University Hospital Gasthuisberg [Leuven], Centre hospitalier universitaire de Nantes (CHU Nantes), 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-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Tel Aviv University (TAU), NUNES, Jacques A, 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), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], 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), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Charité Campus Virchow-Klinikum (CVK), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Chaim Sheba Medical Center, Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], and Gestionnaire, HAL Sorbonne Université 5
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, Calcineurin Inhibitors, matched unrelated donor, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, acute myeloid leukemia, Gastroenterology, 03 medical and health sciences, Cyclosporine A, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Cumulative incidence, MMF, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, business.industry, mycophenolate mofetil, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Mycophenolic Acid, medicine.disease, CsA, 3. Good health, Fludarabine, Calcineurin, Leukemia, Leukemia, Myeloid, Acute, Graft-versus-host disease, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Unrelated Donors, Busulfan, 030215 immunology, medicine.drug
Abstract: International audience; The association of Cyclosporine A (CsA) and mycophenolate mofetil (MMF) has increased in the setting of reduced intensity conditioning (RIC). Nevertheless, the use of CsA or CsA+MMF has not been reported in a large and uniform cohort. We analyzed 497 patients with acute myeloid leukemia in complete remission (CR) who underwent matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). All patients received a fludarabine busulfan RIC regimen and anti-thymocyte globulin (ATG) with either CsA alone or in combination with MMF. The cumulative incidence (CI) of grade II-IV acute GvHD was 27% (95% CI 21-33%) for CsA and 33% (95% CI 27-38%) for CsA+MMF (p = 0.25). The 2-year CI of chronic GvHD was 38% (95% CI 31-45%) and 33% (95% CI 28-39%) for the CsA and the CsA+MMF group, respectively (p = 0.26). On multivariate analysis, no statistically significant differences with respect to relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD were found between the two groups, also when conducting a subgroup analysis in peripheral blood stem cells (PBSC) recipients. Our results support the importance of randomized trial to identify patients who could benefit from the addition of MMF in MUD HSCT.
Published: 2021

48. Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

Author: Norbert Ifrah, Hacene Zerazhi, Pierre-Yves Dumas, Norbert Vey, Isabelle Luquet, Denis Caillot, Marie-Christine Béné, Célestine Simand, Marie-Pierre Ledoux, Véronique Dorvaux, Yosr Hicheri, Anne Banos, Maria Pilar Gallego Hernanz, Chantal Himberlin, Odile Blanchet, Eric Delabesse, Catherine Humbrecht, Pascal Turlure, Arnaud Pigneux, Eric Jourdan, Jacques Delaunay, Didier Bouscary, Emmanuelle Tavernier, Christian Recher, Gaelle Guillerm, Mathilde Hunault-Berger, Romain Guieze, Martin Carre, Anne Bouvier, Jean-Pierre Marolleau, Claude Eric Bulabois, Pascale Cornillet-Lefebvre, Mario Ojeda-Uribe, Marc Bernard, Magda Alexis, Jean-François Hamel, Etienne Daguindau, Pierre Peterlin, Gabrielle Roth Guepin, Emmanuel Gyan, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital privé du Confluent [Nantes], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], CHU Pontchaillou [Rennes], Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), 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), Centre de Ressources Biologiques [CHU Angers], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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], Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Oncology, Adult, Male, Risk, medicine.medical_specialty, NPM1, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Phases of clinical research, Gene mutation, Disease-Free Survival, Cytogenetics, Young Adult, Internal medicine, hemic and lymphatic diseases, CEBPA, Medicine, Cluster Analysis, Humans, Chemotherapy, business.industry, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, General Medicine, Middle Aged, Prognosis, Gemtuzumab, Transplantation, Leukemia, Myeloid, Acute, Karyotyping, Cytogenetic Analysis, Mutation, Female, business
Abstract: International audience; In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (
Published: 2021

49. Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study

Author: Agostino Cortelezzi, André Tichelli, R. F. Duarte, Alicia Rovó, Mutlu Arat, John A. Snowden, Arnon Nagler, S van der Werf, Mohamad Mohty, Peter Dreger, M. Labopin, Nina Salooja, Diana Greenfield, Bernd Metzner, Z. N. Özkurt, Christophe Peczynski, Grzegorz W. Basak, N Kröger, Hélène Schoemans, Pascal Turlure, Gérard Socié, Kate Hill, M. Lupo-Stangellini, Thang S. Han, University of Sheffield [Sheffield], Imperial College London, Centre International des greffes [CHU Saint-Antoine] (EBMT), 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), EBMT Data Office Leiden [Leiden, TheNetherlands], University Hospitals Leuven [Leuven], University of Southampton, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, IRCCS Ospedale San Raffaele [Milan, Italy], Gazi University, Sisli Florence Nightingale Hospital [Istanbul, Turkey], Klinikum Oldenburg [Oldenburg], Zentrum für Kinder- und Jugendmedizin, CHU Limoges, Bern University Hospital [Berne] (Inselspital), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chaim Sheba Medical Center, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Heidelberg, Medical Faculty, University of London [London], University Hospital Basel [Basel], Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Medical University of Warsaw - Poland, Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Graft vs Host Disease, Diseases, Disease, RECOMMENDATIONS, 0302 clinical medicine, ENDOCRINE, Metabolic Syndrome, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, education.field_of_study, COMPLICATIONS, LONG-TERM SURVIVORS, Hematopoietic Stem Cell Transplantation, Haematopoietic cell transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, PREVALENCE, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, surgical procedures, operative, Oncology, Cardiovascular Diseases, 030220 oncology & carcinogenesis, HEALTH, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Population, Immunology, Biophysics, 610 Medicine & health, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Medical research, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Transplantation, Homologous, In patient, Risk factor, education, Transplantation, Science & Technology, CHILDHOOD-CANCER, Vascular disease, business.industry, medicine.disease, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Non interventional, RISK-FACTORS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Metabolic syndrome, business
Abstract: Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p
Published: 2021

50. Prognostic significance of concurrent gene mutations i n intensively treated patients with IDH-mutated AML: an ALFA study

Author: Céline Berthon, Lionel Ades, Nicolas Boissel, Emilie Lemasle, Christian Recher, Xavier Thomas, Nicolas Duployez, Norbert Vey, Raphael Itzykson, Sylvain Chantepie, Karine Celli-Lebras, Arnaud Pigneux, Pascal Turlure, Stéphane de Botton, Claude Preudhomme, Claude Gardin, Denis Caillot, Jean-Pierre Marolleau, Christine Terré, Jean-Baptiste Micol, Hervé Dombret, Thorsten Braun, Juliette Lambert, Emmanuel Raffoux, Jean-Valère Malfuson, Matthieu Duchmann, Cécile Pautas, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Université Paris-Saclay, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Amiens-Picardie, Hôpital Avicenne [AP-HP], Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Henri Mondor, Centre Hospitalier de Versailles André Mignot (CHV), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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), Cellules souches hématopoïétiques et développement des hémopathies myéloïdes (CSHMyelo), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], 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 de Transfusion Sanguine des Armées (CTSA), 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), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Universitaire d'Hématologie (IUH), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [CHU Toulouse], CHU Toulouse [Toulouse], and DESSAIVRE, Louise
Subjects: Male, Oncology, medicine.medical_specialty, NPM1, IDH1, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Abnormal Karyotype, Hematopoietic stem cell transplantation, Gene mutation, medicine.disease_cause, Biochemistry, Disease-Free Survival, DNA Methyltransferase 3A, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Humans, Point Mutation, Medicine, Prospective Studies, In Situ Hybridization, Fluorescence, Aged, Proportional Hazards Models, Retrospective Studies, Chromosome Aberrations, Clinical Trials as Topic, Mutation, Acute leukemia, business.industry, Myeloid leukemia, Cell Biology, Hematology, Middle Aged, Isocitrate Dehydrogenase, Neoplasm Proteins, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Isocitrate dehydrogenase, Female, France, business, Nucleophosmin
Abstract: International audience; In patients with isocitrate dehydrogenase (IDH)-mutated acute myeloid leukemia (AML) treated by intensive chemotherapy (IC), prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are of particular interest with the advent of IDH1/2 mutant inhibitors. We retrospectively analyzed 319 patients with newly diagnosed AML (127 with IDH1, 135 with IDH2R140, and 57 with IDH2R172 mutations) treated with IC in 3 Acute Leukemia French Association prospective trials. In each IDH subgroup, we analyzed the prognostic impact of clinical and genetic covariates, and the role of HSCT. In patients with IDH1 mutations, the presence of NPM1 mutations was the only variable predicting improved overall survival (OS) in multivariate analysis (P< .0001). In IDH2R140-mutated AML, normal karyotype (P = .008) and NPM1 mutations (P = .01) predicted better OS. NPM1 mutations were associated with better disease-free survival (DFS; P = .0009), whereas the presence of DNMT3A mutations was associated with shorter DFS (P = .0006). In IDH2R172-mutated AML, platelet count was the only variable retained in the multivariate model for OS (P = .002). Among nonfavorable European LeukemiaNet 2010-eligible patients, 71 (36%) underwent HSCT in first complete remission (CR1) and had longer OS (P = .03) and DFS (P = .02) than nontransplanted patients. Future clinical trials testing frontline IDH inhibitors combined with IC may consider stratification on NPM1 mutational status, the primary prognostic factor in IDH1- or IDH2R140-mutated AML. HSCT improve OS of nonfavorable IDH1/2-mutated AML and should be fully integrated into the treatment strategy.
Published: 2021

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