39 results on '"G, Damaj"'
Search Results
2. Role of social status and social environment on net survival in patients with chronic lymphocytic leukemia: A high-resolution population-based study
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B. Delapierre, X. Troussard, G. Damaj, O. Dejardin, and L. Tron
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Cancer Research ,History ,Oncology ,Polymers and Plastics ,Epidemiology ,Business and International Management ,Industrial and Manufacturing Engineering - Abstract
The prognostic roles of social status and social environment in chronic lymphocytic leukemia have been highlighted in some solid tumors but remain unclear in hematological malignancies. The objective of this study was to evaluate the influence of individual social status (with socioprofessional category, SPC) and social environment (with European deprivation index, EDI) on net survival in a high-resolution population with CLL.We included CLL patients from the Regional Register of Hematological Malignancies in Normandy belonging to the French Network of Cancer Registries (Francim). The SPC variable was divided into 5 categories: farmers, craftsmen, higher employment, intermediate employment, and workers/employees. Net survival was used to estimate the excess of mortality in CLL independent of other possible causes of death using French life tables. Net survival was estimated with a nonparametric method (Pohar-Perme) and with a flexible excess mortality hazard model. Missing data were handled with multiple imputation.A total of 780 patients were included. The median follow-up was 7.9 years. The crude survival at 10 years was 50%, and the net survival at 10 years was 80%. In multivariate analysis, a higher age (EHR: 1.04 [1.01-1.07]), being a craftsman (EHRSocioprofessional category was a prognostic factor for an excess of mortality in CLL. Craftsmen and workers/employees shared a worse prognosis than workers with higher employment. The social environment was not a prognostic factor. Further work should be performed to explore causal epidemiologic or biological factors and other hematological malignancies.
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- 2022
3. Characteristics and outcomes associated with CD2 and CD25 expression on bone marrow mast cells in patients with systemic mastocytosis.
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Rossignol J, Georgin-Lavialle S, Canioni D, Beganovic O, Brouzes C, Fain O, Heiblig M, Gourguechon C, Guilpain P, Bulai-Livideanu C, Barete S, Agopian J, Brenet F, Dubreuil P, Lemal R, Tournilhac O, Terriou L, Launay D, Bouillet L, Chatain C, Damaj G, Ballul T, Greco C, Polivka L, Frenzel L, Meni C, Bouktit H, Benabou D, Devin C, Gaudy-Marqueste C, Gousseff M, Le Mouel E, Neel A, Ranta D, Jaussaud R, Jo Molina T, Bruneau J, Javier RM, Pelletier F, Castelain F, Retornaz F, Cabrera Q, Zunic P, Gourin MP, Wierzbicka-Hainaut E, Viallard JF, Lavigne C, Hoarau C, Durieu I, Dimicoli-Salazar S, Torregrosa-Diaz JM, Duval A, Garcelon N, Lespinasse J, Soria A, Chantran Y, Arock M, Bodemer C, Lortholary O, Asnafi V, Hermine O, and Lhermitte L
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- 2025
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4. Is ibrutinib-related atrial fibrillation dose dependent? Insights from an individual case level analysis of the World Health Organization pharmacovigilance database.
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Alexandre J, Font J, Angélique DS, Delapierre B, Damaj G, Plane AF, Legallois D, Milliez P, Dolladille C, and Chrétien B
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- Humans, Male, Female, Aged, Middle Aged, Adverse Drug Reaction Reporting Systems statistics & numerical data, Dose-Response Relationship, Drug, Pyrimidines adverse effects, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Aged, 80 and over, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors therapeutic use, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions etiology, Atrial Fibrillation chemically induced, Atrial Fibrillation drug therapy, Adenine analogs & derivatives, Adenine adverse effects, Pharmacovigilance, Piperidines adverse effects, Piperidines administration & dosage, World Health Organization, Pyrazoles adverse effects, Pyrazoles administration & dosage, Databases, Factual
- Abstract
Whether ibrutinib-related atrial fibrillation (IRAF) is a dose-dependent adverse drug reaction (ADR) and whether ibrutinib should be discontinued or dose-reduced in case of IRAF occurrence remains unknown. Using the World Health Organization individual case safety report pharmacovigilance database, VigiBase®, we aimed to determine the association between ibrutinib dosing regimens and IRAF reporting. Ibrutinib daily dose was extracted from IRAF cases from VigiBase® and was divided into 5 ibrutinib dosing regimen (140-280-420-560 and >560 mg/day). Disproportionality analysis was used to evaluate the association between IRAF reporting and ibrutinib daily dose, through logistic regression. Single term deletions produced the ibrutinib daily dose global p-value. Then, a multivariable adjusted reporting odds-ratio with its 95% confidence interval was calculated for each ibrutinib dosing regimen, against the lowest dosing regimen (140 mg/day) as reference. A total of 1162 IRAF cases were identified in VigiBase® (n = 62 for ibrutinib 140 mg/day, 114 for ibrutinib 280 mg/day, 811 for ibrutinib 420 mg/day, 164 for ibrutinib 560 mg/day and 11 for ibrutinib >560 mg/day). After adjustment on several variables of interest, IRAF reporting was not significantly associated with ibrutinib dosing regimen (p = 0.09). Our results from Vigibase® do not support IRAF as a dose-dependent ADR (ClinicalTrial registration number: NCT06224452)., Competing Interests: Competing interests: JA reports honoraria for presentations and consulting fees from Biotronik, Bioserenity, Amgen, BMS, Pfizer, Boerhinger, Bayer, Astra Zeneca, Janssen, Servier, and Novartis, outside of the submitted work. DL reports honoraria for presentations and consulting fees from Astrazeneca, Boehringer Ingelheim, Lilly, Pfizer and Takeda, outside of the submitted work. CD reports honoraria for presentations and consulting fees from Bioserenity and Pfizer, outside of the submitted work. The remaining authors have nothing to disclose., (© 2024. The Author(s).)
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- 2024
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5. Interactions between eosinophils and IL-5Rα-positive mast cells in nonadvanced systemic mastocytosis.
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Lefèvre G, Gibier JB, Bongiovanni A, Lhermitte L, Rossignol J, Anglo E, Dendooven A, Dubois R, Terriou L, Launay D, Barete S, Esnault S, Frenzel L, Gourguechon C, Ballul T, Dezoteux F, Staumont-Salle D, Copin MC, Rignault-Bricard R, Maciel TT, Damaj G, Tardivel M, Crinquette-Verhasselt M, Dubreuil P, Maouche-Chrétien L, Bruneau J, Lortholary O, Duployez N, Behal H, Molina TJ, and Hermine O
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- Humans, Male, Female, Middle Aged, Adult, Aged, Bone Marrow pathology, Bone Marrow immunology, Bone Marrow metabolism, Tryptases metabolism, Tryptases blood, Cell Communication immunology, Cell Degranulation, Eosinophil Peroxidase metabolism, Mast Cells immunology, Mast Cells metabolism, Mast Cells pathology, Eosinophils immunology, Eosinophils pathology, Mastocytosis, Systemic pathology, Mastocytosis, Systemic immunology, Mastocytosis, Systemic metabolism, Mastocytosis, Systemic diagnosis, Interleukin-5 Receptor alpha Subunit metabolism, Interleukin-5 Receptor alpha Subunit immunology
- Abstract
Background: Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown., Objective: We described blood and BM eosinophil characteristics in SM., Methods: A large collection of BM biopsy samples was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence., Results: Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in nonadvanced SM (n = 37 BM biopsy samples) compared with both controls (n = 8, P = .0003) and advanced SM (n = 24, P = .014). In nonadvanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r = 0.38, P = .038), eosinophils count in BM biopsy samples (r = 0.45, P = .007), EPX staining (r = 0.37, P = .035), and eosinophil degranulation (r = 0.39, P = .023). Eosinophil counts in BM biopsy samples also correlated with MC counts (r = 0.47, P = .006) and KIT staining surface (r = 0.49, P = .003). BM MCs expressed IL-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils displayed several increased surface markers compared with controls, suggesting an activated state., Conclusion: Our data suggest possible cross talk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in nonadvanced SM not fully controlled by other therapies., Competing Interests: Disclosure statement Funding provided by GSK (ISS 10889). The authors are solely responsible for final content and interpretation. Disclosure of potential conflict of interest: O. Hermine received research funds from Blueprint, AB Science, Alexion, and BMS; and is cofounder and shareholder of Innatherys and AB Science. D. Launay received consulting fees from AstraZeneca. G. Lefèvre received consulting fees from AstraZeneca, GSK, and Sanofi; and research funds from AstraZeneca and GSK. J. Rossignol received consulting fees from Blueprint and research funds from Novartis. D. Staumont-Salle received consulting fees from AstraZeneca, GSK, Novartis, and Sanofi-Regeneron. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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6. High-dose chemotherapy with autologous haematopoietic stem cell transplantation in patients with isolated vitreoretinal lymphoma: a LOC network study.
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Mainguy A, Soussain C, Touitou V, Bennedjai A, Kodjikian L, Ghesquières H, Damaj G, Gressin R, Ducloyer JB, Chinot O, Vautier A, Moluçon-Chabrot C, Ahle G, Taillandier L, Marolleau JP, Chauchet A, Jardin F, Cassoux N, Malaise D, Toutée A, Touhami S, Le Garff-Tavernier M, Hoang-Xuan K, Choquet S, and Houillier C
- Abstract
Despite its indolent evolution, vitreoretinal lymphoma (VRL) has a poor prognosis due to a major risk of relapse in the central nervous system (CNS) and may necessitate aggressive therapy. However, the use of high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is poorly documented. We retrospectively analysed from the French LOC network database the adult immunocompetent patients treated with HCT-ASCT for isolated VRL. Thirty-eight patients underwent consolidation with HCT-ASCT for isolated VRL between 2008 and 2019 after induction chemotherapy. Twenty patients had primary VRL, and 18 had an isolated VRL relapse of a primary CNS lymphoma. Three patients underwent HCT-ASCT in first-line treatment, 24 in second-line treatment, and 11 in subsequent lines. At HCT-ASCT, the median age was 61 years, and the median KPS was 90. Thirty-two patients (84%) received high-dose thiotepa-based HCT. One patient (3%) died from HCT-ASCT toxicity. Nineteen (50%) patients relapsed after HCT-ASCT, including 17 cases occurring in the brain. The median progression-free survival, brain-free survival and overall survival from HCT-ASCT were 96, 113 and 92 months, respectively. HCT-ASCT represents an effective therapeutic strategy for select VRL patients, with a tolerable safety profile. However, the risk of subsequent brain relapse remains significant., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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7. Long-Term Follow-Up of the Prospective Randomized AATT Study (Autologous or Allogeneic Transplantation in Patients With Peripheral T-Cell Lymphoma).
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Tournilhac O, Altmann B, Friedrichs B, Bouabdallah K, Leclerc M, Cartron G, Turlure P, Reimer P, Wagner-Drouet E, Sanhes L, Houot R, Roussel M, Kroschinsky F, Dreger P, Viardot A, de Leval L, Rosenwald A, Gaulard P, Wulf G, Villate A, Latiere C, Elmaagacli A, Glass B, Poeschel V, Damaj G, Sibon D, Durot E, Bilger K, Banos A, Haenel M, Dreyling M, Keller U, Tiab M, Drenou B, Cornillon J, Nguyen S, Robin M, Nickelsen M, Trümper L, Lenz G, Ziepert M, and Schmitz N
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- Humans, Follow-Up Studies, Middle Aged, Adult, Male, Female, Prospective Studies, Young Adult, Time Factors, Aged, Lymphoma, T-Cell, Peripheral therapy, Lymphoma, T-Cell, Peripheral mortality, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation methods, Transplantation, Homologous
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Primary analysis of the phase III randomized AATT study showed that younger patients with peripheral T-cell lymphoma (PTCL) consolidated with autologous or allogeneic transplantation (alloSCT) had similar event-free survival (EFS) and overall survival (OS). Seven-year EFS of patients randomly assigned to alloSCT was 38% (95% CI, 25 to 52) compared with 34% (95% CI, 22 to 47) for patients randomly assigned to autologous transplantation of hematopoietic stem cells (autoSCT); OS was 55% (95% CI, 41 to 69) and 61% (95% CI, 47 to 74). Among patients undergoing alloSCT (n = 26) or autoSCT (n = 41) on study, the cumulative progression/relapse rate was 8% (95% CI, 0 to 19) and 55% (95% CI, 35 to 74). Nonrelapse mortality (NRM) was 31% (95% CI, 13 to 49) and 3% (95% CI, 0 to 8) after alloSCT and autoSCT, respectively. Fifteen of 30 patients with early progression and 11 of 20 patients with progression/relapse after autoSCT received alloSCT. Seven-year OS after salvage alloSCT was 61% (95% CI, 47 to 74); NRM was 23% (95% CI, 6 to 40). Long-term follow-up documents the strong graft versus lymphoma effect of alloSCT independent of the timing of transplantation. Survival of patients unable to undergo transplantation was dismal. AlloSCT is the treatment of choice for younger, transplant-eligible patients with relapsed/refractory PTCL. AlloSCT is currently not recommended as part of first-line consolidation.
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- 2024
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8. Comparison of prognostic scores according to WHO classification in 170 patients with advanced mastocytosis and C-finding treated with midostaurin.
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Heiblig M, Gourguechon C, Guilpain P, Bulai-Livideanu C, Barete S, Chantran Y, Agopian J, Brenet F, Dubreuil P, Lespinasse J, Lemal R, Tournilhac O, Terriou L, Launay D, Bouillet L, Chatain C, Damaj G, Ballul T, Greco C, Polivka L, Frenzel L, Meni C, Bouktit H, Benabou D, Gaudy-Marqueste C, Gousseff M, Le Mouel E, Neel A, Ranta D, Jaussaud R, Molina TJ, Bruneau J, Villarese P, Lhermitte L, Maouche-Chrétien L, Temple M, Kosmider O, Javier RM, Pelletier F, Castelain F, Retornaz F, Cabrera Q, Zunic P, Gourin MP, Wierzbicka-Hainaut E, Viallard JF, Lavigne C, Hoarau C, Durieu I, Dimicoli-Salazar S, Torregrosa-Diaz JM, Wemeau M, Soria A, Arock M, Bodemer C, Lortholary O, Hermine O, and Rossignol J
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- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Prognosis, Adult, World Health Organization, Aged, 80 and over, Protein Kinase Inhibitors therapeutic use, Leukemia, Mast-Cell drug therapy, Hematologic Neoplasms drug therapy, Hematologic Neoplasms mortality, Staurosporine analogs & derivatives, Staurosporine therapeutic use, Mastocytosis, Systemic drug therapy, Mastocytosis, Systemic mortality, Mastocytosis, Systemic classification, Mastocytosis, Systemic diagnosis
- Abstract
Advanced systemic mastocytosis (AdvSM) encompasses heterogeneous mastocytosis subtypes and is associated with poor outcomes. Although midostaurin was the first tyrosine kinase inhibitor to be approved for AdvSM patients, long-lasting responses are limited. The mutation-Adjusted Risk Score (MARS), the International Prognostic Scoring System for mastocytosis (IPSM) and the Global Prognostic Score for Systemic Mastocytosis (GPSM) have been established to characterize the outcomes of patients with overall AdvSM. However, given the outcome's dependency on the AdvSM subtype, prognostic characterization within each subtype is critical. We aimed to study the predictive ability using Harrell's concordance index of prognostic scores according to the AdvSM subtype. We conducted a nationwide retrospective study using the French mastocytosis reference center's registry and included all midostaurin-treated patients with C finding. Overall, 170 patients were identified: 46 aggressive SM (ASM), 11 mast cell leukemia (MCL), and 113 SM with associated hematological neoplasm (SM-AHN). All risk scores improved their discriminative value for overall survival (OS) when combined with the AdvSM subtype. The best predictive value was for adjusted MARS (C-index = 0.689), followed by GPSM (C-index = 0.677) and IPSM (C-index = 0.618). In a multivariable analysis, MARS stratification and the AdvSM subtype were both prognostic for OS. Accordingly, five subgroups of patients with AdvSM and a different median OS were identified: 9.9 months for MCL, 24 months for intermediate/high-risk SM-AHN, 33 months for intermediate/high-risk ASM, 58 months for low-risk SM-AHN and was not reached for low-risk ASM (p < 0.001). The AdvSM subtype and the MARS are the most predictive of OS and should prompt specific management., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)
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- 2024
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9. Modeling NK-cell lymphoma in mice reveals its cell-of-origin and microenvironmental changes and identifies therapeutic targets.
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Koya J, Tanigawa T, Mizuno K, Kim H, Ito Y, Yuasa M, Yamaguchi K, Kogure Y, Saito Y, Shingaki S, Tabata M, Murakami K, Chiba K, Okada A, Shiraishi Y, Marouf A, Liévin R, Chaubard S, Jaccard A, Hermine O, de Leval L, Tournilhac O, Damaj G, Gaulard P, Couronné L, Yasui T, Nakashima K, Miyoshi H, Ohshima K, and Kataoka K
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- Animals, Mice, Humans, Mice, Knockout, Disease Models, Animal, Interferon-gamma metabolism, Receptors, CXCR6 metabolism, Receptors, CXCR6 genetics, Chemokine CXCL16 metabolism, Chemokine CXCL16 genetics, Herpesvirus 4, Human, Gene Expression Regulation, Neoplastic, Signal Transduction, Salivary Glands pathology, Salivary Glands metabolism, Myeloid Cells metabolism, Cell Line, Tumor, Mice, Inbred C57BL, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Tumor Microenvironment immunology, Lymphoma, Extranodal NK-T-Cell genetics, Lymphoma, Extranodal NK-T-Cell metabolism, Lymphoma, Extranodal NK-T-Cell virology, Lymphoma, Extranodal NK-T-Cell pathology, Proto-Oncogene Proteins c-myc metabolism, Proto-Oncogene Proteins c-myc genetics, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 genetics
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Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm preferentially involving the upper aerodigestive tract. Here we show that NK-cell-specific Trp53 disruption in mice leads to the development of NK-cell lymphomas after long latency, which involve not only the hematopoietic system but also the salivary glands. Before tumor onset, Trp53 knockout causes extensive gene expression changes, resulting in immature NK-cell expansion, exclusively in the salivary glands. Both human and murine NK-cell lymphomas express tissue-resident markers, suggesting tissue-resident NK cells as their cell-of-origin. Murine NK-cell lymphomas show recurrent Myc amplifications and upregulation of MYC target gene signatures. EBV-encoded latent membrane protein 1 expression accelerates NK-cell lymphomagenesis and causes diverse microenvironmental changes, particularly myeloid propagation, through interferon-γ signaling. In turn, myeloid cells support tumor cells via CXCL16-CXCR6 signaling and its inhibition is effective against NK-cell tumors in vivo. Remarkably, KLRG1-expressing cells expand in the tumor and are capable of repopulating tumors in secondary recipients. Furthermore, targeting KLRG1 alone or combined with MYC inhibition using an eIF4 inhibitor is effective against NK-cell tumors. Therefore, our observations provide insights into the pathogenesis and highlight potential therapeutic targets, including CXCL16, KLRG1, and MYC, in ENKTCL, which can help improve its diagnostic and therapeutic strategies., (© 2024. The Author(s).)
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- 2024
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10. [Nurturing and growing a community of department heads: Act 2 in haematology].
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Houot R, Calmettes C, Park S, Pascal L, Peffault de Latour R, Pigneux A, Quinquenel A, Raffoux E, Thieblemont C, Touati M, Trebouet A, Vaida I, Wémeau M, Bastie JN, Bay JO, Cluzeau T, Cornillon J, Damaj G, Deconinck E, Feugier P, Fornecker LM, Gay J, Hermine O, Hospital MA, Hunault M, Jaccard A, Jardin F, Le Calloch R, Legros L, Leleu X, Lemonnier F, Malfuson JV, Morel P, Ochmann M, Orsini-Piocelle F, and Gyan E
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- Humans, France, Peer Group, Hematology organization & administration, Hospital Departments organization & administration
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In response to the French hospital system crisis and the challenges faced by the heads of departments, we have undertaken an initiative to create a community of heads of haematology departments willing to assist each other. Our inaugural seminar, held in January 2023, established the foundational "core" group of heads of department. Throughout 2023, this emerging community has prospered, offering sustained support to peers. In January 2024, we broadened our community to include other heads of departments, following a second seminar gathering 36 participants. During this event, we took the time to exchange thoughts and reflect on our missions. Building on the experience of guest speakers and employing methods of co-development and co-construction in plenary sessions, small-group workshops, and social gathering, we were able to discover and experience the collective intelligence, creativity, strength, and support stemming from such a group. This peer community of heads of departments stands as a powerful tool for management support, whereby personal experiences nourish and enrich the experience of others. We hope that our initiative will inspire heads of departments from other specialties so that, together, we can better work towards our missions as heads of departments and collaborate on rebuilding the hospital "from the bottom up"., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
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- 2024
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11. Efficacy of ruxolitinib in the treatment of relapsed/refractory large granular lymphocytic leukaemia.
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Marchand T, Pastoret C, Damaj G, Lebouvier A, Herbaux C, Moignet A, Pavlosky M, Pavlosky A, Blouet A, Eloit M, Launay V, Lebreton P, Stamatoullas A, Nilsson C, Ochmann M, Prola J, and Lamy T
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- Humans, Female, Male, Middle Aged, Aged, Aged, 80 and over, Adult, Recurrence, Treatment Outcome, Nitriles, Pyrazoles therapeutic use, Pyrimidines therapeutic use, Leukemia, Large Granular Lymphocytic drug therapy
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Large granular lymphocytic (LGL) leukaemia is a rare chronic lymphoproliferative disorder characterized by an expansion of cytotoxic T or NK cells. Despite a usually indolent evolution, most patients will require a treatment over the course of the disease because of cytopenia or symptomatic associated autoimmune disorders. First-line treatment is based on immunosuppressive agents, namely cyclophosphamide, methotrexate and ciclosporin. However, relapses are frequent, and there is no consensus on the management of relapsed/refractory patients. The implication of the JAK/STAT pathway in the pathogenesis of this disease has prompted our group to propose treatment with ruxolitinib. A series of 21 patients who received this regimen is reported here. Ten patients (47.6%) were refractory to the three main immunosuppressive drugs at the time of ruxolitinib initiation. Ruxolitinib yielded an overall response rate of 86% (n = 18/21), including 3 complete responses and 15 partial responses. With a median follow-up of 9 months, the median response duration was 4 months. One-year event-free survival and 1-year overall survival were 57% and 83% respectively. Mild side effects were observed. Biological parameters, notably neutropenia and anaemia, improved significantly, and complete molecular responses were evidenced. This study supports ruxolitinib as a valid option for the treatment of relapsed/refractory LGL leukaemia., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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12. Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma.
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Sarkozy C, Callanan M, Thieblemont C, Obéric L, Burroni B, Bouabdallah K, Damaj G, Tessoulin B, Ribrag V, Houot R, Morschhauser F, Griolet S, Joubert C, Cacheux V, Delwail V, Safar V, Gressin R, Cheminant M, Delfau-Larue MH, Hermine O, Macintyre E, and Le Gouill S
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- Humans, Male, Female, Middle Aged, Aged, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Adult, Hematopoietic Stem Cell Transplantation, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Progression-Free Survival, Neoplasm, Residual, Prospective Studies, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell therapy, Lymphoma, Mantle-Cell pathology, Rituximab administration & dosage, Rituximab therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage
- Abstract
Abstract: Obinutuzumab (O) and rituximab (R) are 2 CD antibodies that have never been compared in a prospective randomized trial of mantle cell lymphoma (MCL). Herein, we report the long-term outcome of the LyMa-101 trial, in which newly diagnosed patients with MCL were treated with chemotherapy plus O before transplantation, followed by O maintenance (O group). We then compared these patients with those treated with the same treatment design with R instead of O (R group). A propensity score matching (PSM) was used to compare the 2 populations (O vs R groups) in terms of measurable residual disease (MRD) at the end of induction (EOI), progression-free survival (PFS), and overall survival (OS). In LyMa-101, the estimated 5-year PFS and OS after inclusion (n = 85) were 83.4% (95% confidence interval [CI], 73.5-89.8) and 86.9% (95% CI, 77.6-92.5), respectively. At EOI, patients treated in the O group had more frequent bone marrow MRD negativity than those treated in the R group (83.1% vs 63.4%; χ2, P = .007). PSM resulted in 2 sets of 82 patients with comparable characteristics at inclusion. From treatment initiation, the O group had a longer estimated 5-year PFS (P = .029; 82.8% vs 66.6%; hazard ratio [HR], 1.99; 95% confidence interval (CI), 1.05-3.76) and OS (P = .039; 86.4% vs 71.4%; HR, 2.08; 95% CI, 1.01-4.16) compared with the R group. Causes of death were comparable in the 2 groups, the most common cause being lymphoma. O before transplantation and in maintenance provides better disease control and enhances PFS and OS compared with R in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT00921414 and NCT02896582., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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13. Comprehensive Genetic Profiling Reveals Frequent Alterations of Driver Genes on the X Chromosome in Extranodal NK/T-cell Lymphoma.
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Ito Y, Marouf A, Kogure Y, Koya J, Liévin R, Bruneau J, Tabata M, Saito Y, Shingaki S, Yuasa M, Yamaguchi K, Murakami K, Weil R, Vavasseur M, Andrieu GP, Latiri M, Veleanu L, Dussiot M, André I, Joshi A, Lagresle-Peyrou C, Magerus A, Chaubard S, Lavergne D, Bachy E, Brunet E, Fataccioli V, Brouzes C, Laurent C, de Leval L, Traverse-Glehen A, Bossard C, Parrens M, Meignin V, Philippe L, Rossignol J, Suarez F, Michot JM, Tournilhac O, Damaj G, Lemonnier F, Bôle-Feysot C, Nitschké P, Tesson B, Laurent C, Molina T, Asnafi V, Watatani Y, Chiba K, Okada A, Shiraishi Y, Tsukita S, Izutsu K, Miyoshi H, Ohshima K, Sakata S, Dobashi A, Takeuchi K, Sanada M, Gaulard P, Jaccard A, Ogawa S, Hermine O, Kataoka K, and Couronné L
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- Humans, Male, Female, DNA Copy Number Variations, Mutation, Middle Aged, Animals, Adult, Mice, Prognosis, Aged, Gene Expression Profiling, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Young Adult, Epstein-Barr Virus Infections genetics, Epstein-Barr Virus Infections virology, Epstein-Barr Virus Infections complications, Chromosomes, Human, X genetics, Lymphoma, Extranodal NK-T-Cell genetics, Lymphoma, Extranodal NK-T-Cell virology, Lymphoma, Extranodal NK-T-Cell pathology, Lymphoma, Extranodal NK-T-Cell metabolism
- Abstract
Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. In this study, we performed a comprehensive genetic analysis of 178 ENKTCL cases to delineate the landscape of mutations, copy number alterations (CNA), and structural variations, identifying 34 driver genes including six previously unappreciated ones, namely, HLA-B, HLA-C, ROBO1, CD58, POT1, and MAP2K1. Among them, CD274 (24%) was the most frequently altered, followed by TP53 (20%), CDKN2A (19%), ARID1A (15%), HLA-A (15%), BCOR (14%), and MSN (14%). Chromosome X losses were the most common arm-level CNAs in females (∼40%), and alterations of four X-linked driver genes (MSN, BCOR, DDX3X, and KDM6A) were more frequent in males and females harboring chromosome X losses. Among X-linked drivers, MSN was the most recurrently altered, and its expression was lost in approximately one-third of cases using immunohistochemical analysis. Functional studies of human cell lines showed that MSN disruption promoted cell proliferation and NF-κB activation. Moreover, MSN inactivation increased sensitivity to NF-κB inhibition in vitro and in vivo. In addition, recurrent deletions were observed at the origin of replication in the EBV genome (6%). Finally, by integrating the 34 drivers and 19 significant arm-level CNAs, nonnegative matrix factorization and consensus clustering identified two molecular groups with different genetic features and prognoses irrespective of clinical prognostic factors. Together, these findings could help improve diagnostic and therapeutic strategies in ENKTCL. Significance: Integrative genetic analyses and functional studies in extranodal NK/T-cell lymphoma identify frequent disruptions of X-linked drivers, reveal prognostic molecular subgroups, and uncover recurrent MSN alterations that confer sensitivity to NF-κB inhibition., (©2024 American Association for Cancer Research.)
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- 2024
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14. Histological characterization of liver involvement in systemic mastocytosis.
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Rossignol J, Canioni D, Aouba A, Bulai-Livideanu C, Barete S, Lancesseur C, Polivka L, Madrange M, Ballul T, Neuraz A, Greco C, Agopian J, Brenet F, Dubreuil P, Lemal R, Tournilhac O, Terriou L, Launay D, Bouillet L, Gourguechon C, Frenzel L, Meni C, Gaudy-Marqueste C, Gousseff M, Le Mouel E, Hamidou M, Neel A, Ranta D, Jaussaud R, Guilpain P, Molina TJ, Bruneau J, Lhermitte L, Garcelon N, Javier RM, Pelletier F, Castelain F, Retornaz F, Cabrera Q, Zunic P, Gourin MP, Wierzbicka-Hainaut E, Viallard JF, Lavigne C, Hoarau C, Durieu I, Heiblig M, Dimicoli-Salazar S, Torregrosa-Diaz JM, Soria A, Arock M, Lortholary O, Bodemer C, Pol S, Mallet V, Hermine O, and Damaj G
- Subjects
- Humans, Retrospective Studies, Female, Male, Middle Aged, Adult, Biopsy, Aged, Hypertension, Portal pathology, Hypertension, Portal etiology, France, Liver Cirrhosis pathology, Mast Cells pathology, Alkaline Phosphatase blood, Prognosis, Mastocytosis, Systemic pathology, Mastocytosis, Systemic complications, Liver pathology, Hepatomegaly pathology, Hepatomegaly etiology
- Abstract
Background and Aims: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools., Methods: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist., Results: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002)., Conclusions: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2024
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15. Long-term analysis of the RiBVD phase II trial reveals the unfavorable impact of TP53 mutations and hypoalbuminemia in older adults with mantle cell lymphoma; for the LYSA group.
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Carras S, Torroja A, Emadali A, Montaut E, Daguindau N, Tempescul A, Moreau A, Tchernonog E, Schmitt A, Houot R, Dartigeas C, Barbieux S, Corm S, Banos A, Fouillet L, Dupuis J, Macro M, Fleury J, Jardin F, Sarkozy C, Damaj G, Feugier P, Fornecker LM, Chabrot C, Dorvaux V, Bouabdallah K, Amorim S, Garidi R, Voillat L, Joly B, Morineau N, Moles MP, Zerazhi H, Fontan J, Arkam Y, Alexis M, Delwail V, Vilque JP, Ysebaert L, Burroni B, Callanan M, Le Gouill S, and Gressin R
- Subjects
- Humans, Aged, Female, Male, Aged, 80 and over, Prognosis, Rituximab therapeutic use, Rituximab administration & dosage, Treatment Outcome, Bendamustine Hydrochloride administration & dosage, Bendamustine Hydrochloride therapeutic use, Dexamethasone therapeutic use, Dexamethasone administration & dosage, Doxorubicin therapeutic use, Doxorubicin administration & dosage, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell pathology, Tumor Suppressor Protein p53 genetics, Mutation, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Hypoalbuminemia etiology
- Abstract
Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (rituximab, bendamustine, velcade and dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients over the age of 65. We have now re-examined the classic prognostic factors, adding an assessment of TP53 mutation status. Patients (N=74; median age 73 years) were treated with the RiBVD combination. Median progression-free survival (mPFS) was 79 months and median overall survival (mOS) was 111 months. TP53 mutation status was available for 54/74 (73%) patients. TP53 mutations (TP53mt) were found in 12 patients (22.2%). In multivariate analysis, among the prognostic factors (PF) evaluated, only TP53mt and an albumin level (Alb) 3.6 g/dL were independently associated with a shorter mPFS. A hazard ratio (HR) of 3.16 (1.3-9.9, P=0.014) was obtained for TP53mt versus TP53 wild-type (wt), and 3.6 (1.39-9.5, P=0.009) for Alb <3.6 g/dL versus Alb ≥3.6 g/dL. In terms of mOS, multivariate analysis identified three PF: TP53mt (HR: 5.9 [1.77-19.5, P=0.004]), Alb <3.6 g/dL (HR: 5.2 [1.46- 18.5, P=0.011]), and ECOG=2 (HR: 3.7 [1.31-10.6, P=0.014]). Finally, a score combining TP53 status and Alb distinguished three populations based on the presence of 0, 1, or 2 PF. For these populations, mPFS was 7.8 years, 28 months, and 2.5 months, respectively. Our prolonged follow-up confirmed the efficacy of the RiBVD regimen, comparing it favorably to other regimens. TP53mt and hypoalbuminemia emerge as strong PF that can be easily integrated into prognostic scores for older adult patients with MCL.
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- 2024
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16. Efficacy and safety of mammalian target of rapamycin inhibitors in systemic mastocytosis: A nationwide French pilot study.
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Moraly J, Rossignol J, Rouzaud C, Gabas T, Bouktit H, Lhermitte L, Canioni D, Fraitag S, Bruneau J, Barete S, Suarez F, Ballul T, Meni C, Polivka L, Terriou L, Launay D, Bouillet L, Gaudy-Marqueste C, Gousseff M, Le Mouel E, Neel A, Ranta D, Jaussaud R, Guilpain P, Frenzel L, Agopian J, Dubreuil P, Greco C, Dimicoli-Salazar S, Heiblig M, Gourguechon C, Tournilhac O, Javier RM, Castelain F, Cabrera Q, Gourin MP, Wierzbicka-Hainaut E, Torregrosa-Diaz JM, Bulai C, Lavigne C, Hoarau C, Arock M, Damaj G, Lortholary O, and Hermine O
- Subjects
- Humans, Pilot Projects, Female, Male, Middle Aged, Adult, France, Aged, Proto-Oncogene Proteins c-kit genetics, Proto-Oncogene Proteins c-kit antagonists & inhibitors, Everolimus therapeutic use, Everolimus adverse effects, Treatment Outcome, TOR Serine-Threonine Kinases antagonists & inhibitors, Aged, 80 and over, Mastocytosis, Systemic drug therapy, Sirolimus therapeutic use, Sirolimus adverse effects, MTOR Inhibitors therapeutic use
- Abstract
Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
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- 2024
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17. Allogeneic haematopoietic cell transplantation for advanced systemic mastocytosis: Best practice recommendations on behalf of the EBMT Practice Harmonisation and Guidelines Committee.
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McLornan DP, Czerw T, Damaj G, Ethell M, Gurnari C, Hernández-Boluda JC, Polverelli N, Schwaab J, Sockel K, Raffaella G, Onida F, Sánchez-Ortega I, Battipaglia G, Elena C, Gotlib J, Reiter A, Rossignol J, Ustun C, Valent P, Yakoub-Agha I, and Radia DH
- Subjects
- Humans, Proto-Oncogene Proteins c-kit genetics, Mast Cells, Mastocytosis, Systemic therapy, Mastocytosis, Systemic drug therapy, Antineoplastic Agents therapeutic use, Mastocytosis therapy, Leukemia, Mast-Cell drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Systemic Mastocytosis (SM) is a multifaceted clinically heterogeneous disease. Advanced SM (AdvSM) comprises three entities: aggressive SM (ASM), mast cell leukaemia (MCL) and SM with an associated hematologic neoplasm (SM-AHN), the latter accounting for 60-70% of all AdvSM cases. Detection of a disease-triggering mutation in the KIT gene (esp. KIT D816V) in >90% of the patients with ASM or SM-AHN has led to a significant improvement in therapeutic options by the implementation of two KIT-targeting kinase inhibitors: midostaurin and avapritinib. Although complete remissions have been reported, neither of these targeted agents is 'curative' in all patients and the duration of responses varies. The median overall survival, depending on the WHO subtype and scoring result, is approximately 1 to 4 years. Although the European Competence Network on Mastocytosis (ECNM) and American Initiative in Mast Cell Diseases (AIM) consensus groups recommend allogeneic haematopoietic cell transplantation (allo-HCT) in drug-resistant and other high-risk patients, there is a relative lack of information to guide clinicians on which patients with AdvSM should be considered for transplant, and how KIT inhibitors may fit into the transplant algorithm, including their use pre- and post-transplant to optimise outcomes. Following the generation of an expert panel with a specialist interest in allo-HCT and mastocytosis, these best practice recommendations were generated according to the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonisation and guidelines and ECNM methodology. We aim to provide a practical, clinically relevant and up-to-date framework to guide allo-HCT in AdvsM in 2024 and beyond., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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18. Toxicities, intensive care management, and outcome of chimeric antigen receptor T cells in adults: an update.
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Bellal M, Malherbe J, Damaj G, and Du Cheyron D
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- Adult, Humans, B-Lymphocytes, Critical Care, T-Lymphocytes, Receptors, Chimeric Antigen therapeutic use, Hematologic Neoplasms therapy
- Abstract
Background: Chimeric antigen receptor T cells are a promising new immunotherapy for haematological malignancies. Six CAR-T cells products are currently available for adult patients with refractory or relapsed high-grade B cell malignancies, but they are associated with severe life-threatening toxicities and side effects that may require admission to ICU., Objective: The aim of this short pragmatic review is to synthesize for intensivists the knowledge on CAR-T cell therapy with emphasis on CAR-T cell-induced toxicities and ICU management of complications according to international recommendations, outcomes and future issues., (© 2024. The Author(s).)
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- 2024
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19. Long-Term Follow-Up of Rituximab Maintenance in Young Patients With Mantle-Cell Lymphoma Included in the LYMA Trial: A LYSA Study.
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Sarkozy C, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Damaj G, Gastinne T, Tessoulin B, Ribrag V, Casasnovas O, Haioun C, Houot R, Jardin F, Van Den Neste E, Cheminant M, Morschhauser F, Callanan M, Safar V, Gressin R, Hermine O, and Le Gouill S
- Subjects
- Adult, Humans, Rituximab therapeutic use, Follow-Up Studies, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols adverse effects, Lymphoma, Mantle-Cell drug therapy, Hematopoietic Stem Cell Transplantation methods
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The LYMA trial demonstrated the benefit of rituximab maintenance (RM) in first-line young patients with mantle-cell lymphoma. In this prolonged follow-up of 7.5 years (95% CI, 7.4 to 7.7) from inclusion, the median progression-free survival (PFS) and overall survival (OS) for the full population were not reached (NR) with a 7-year PFS of 55.5% (95% CI, 49.5 to 61) and OS of 69.5% (95% CI, 63.8 to 74.5). The EFS remained statistically superior in favor of RM (median NR v 5.8 years, P < .0001; HR, 0.39 [95% CI, 0.52 to 0.6] and 7-year estimate, 76.2% versus 46% for RM and observation, respectively). Similarly, RM prolonged PFS (estimated PFS at 7 years, 78.5% v 47.4% and HR, 0.36 [95% CI, 0.23 to 0.56] for RM and observation, respectively, P < .0001). The 7-year OS estimate was 83.2% versus 72.2%, respectively ( P = .088, HR, 0.63 [95% CI, 0.37 to 1.08]). Cause of death was not significantly distinct between the two groups, with lymphoma being the leading cause with a very low rate of infection-related death. Overall, the PFS benefit of RM after autologous stem cell transplantation remains after 7-year follow-up, and RM was not associated with an increase in infection-related mortality, making this strategy a safe standard of care with long-term follow-up.
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- 2024
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20. Challenges for quality and utilization of real-world data for diffuse large B-cell lymphoma in REALYSA, a LYSA cohort.
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Ghesquières H, Cherblanc F, Belot A, Micon S, Bouabdallah KK, Esnault C, Fornecker LM, Thokagevistk K, Bonjour M, Bijou F, Haioun C, Morineau N, Ysebaert L, Damaj G, Tessoulin B, Guidez S, Morschhauser F, Thiéblemont C, Chauchet A, Gressin R, Jardin F, Fruchart C, Labouré G, Fouillet L, Lionne-Huyghe P, Bonnet A, Lebras L, Amorim S, Leyronnas C, Olivier G, Guieze R, Houot R, Launay V, Drénou B, Fitoussi O, Detourmignies L, Abraham J, Soussain C, Lachenal F, Pica GM, Fogarty P, Cony-Makhoul P, Bernier A, Le Guyader-Peyrou S, Monnereau A, Boissard F, Rossi C, and Camus V
- Subjects
- Adult, Humans, Aged, Prospective Studies, Retrospective Studies, Rituximab therapeutic use, Cyclophosphamide therapeutic use, Prednisone therapeutic use, Vincristine therapeutic use, Doxorubicin therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Abstract: Real-world data (RWD) are essential to complement clinical trial (CT) data, but major challenges remain, such as data quality. REal world dAta in LYmphoma and Survival in Adults (REALYSA) is a prospective noninterventional multicentric cohort started in 2018 that included patients newly diagnosed with lymphoma in France. Herein is a proof-of-concept analysis on patients with first-line diffuse large B-cell lymphoma (DLBCL) to (1) evaluate the capacity of the cohort to provide robust data through a multistep validation process; (2) assess the consistency of the results; and (3) conduct an exploratory transportability assessment of 2 recent phase 3 CTs (POLARIX and SENIOR). The analysis population comprised 645 patients with DLBCL included before 31 March 2021 who received immunochemotherapy and for whom 3589 queries were generated, resulting in high data completeness (<4% missing data). Median age was 66 years, with mostly advanced-stage disease and high international prognostic index (IPI) score. Treatments were mostly rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP 75%) and reduced dose R-CHOP (13%). Estimated 1-year event-free survival (EFS) and overall survival rates were 77.9% and 90.0%, respectively (median follow-up, 9.9 months). Regarding transportability, when applying the CT's main inclusion criteria (age, performance status, and IPI), outcomes seemed comparable between patients in REALYSA and standard arms of POLARIX (1-year progression-free survival 79.8% vs 79.8%) and SENIOR (1-year EFS, 64.5% vs 60.0%). With its rigorous data validation process, REALYSA provides high-quality RWD, thus constituting a platform for numerous scientific purposes. The REALYSA study was registered at www.clinicaltrials.gov as #NCT03869619., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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21. Correction to: Prognostic relevance of sarcopenia, geriatric, and nutritional assessments in older patients with diffuse large B‑cell lymphoma: results of a multicentric prospective cohort study.
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Pénichoux J, Lanic H, Thill C, Ménard AL, Camus V, Stamatoullas A, Lemasle E, Leprêtre S, Lenain P, Contentin N, Kraut-Tauzia J, Fruchart C, Kammoun L, Damaj G, Farge A, Delette C, Modzelewski R, Vaudaux S, Pépin LF, Tilly H, and Jardin F
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- 2024
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22. Pathophysiologic implications of elevated prevalence of hereditary alpha-tryptasemia in all mastocytosis subtypes.
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Polivka L, Madrange M, Bulai-Livideanu C, Barete S, Ballul T, Neuraz A, Greco C, Agopian J, Brenet F, Dubreuil P, Burdet C, Lemal R, Tournilhac O, Terriou L, Launay D, Bouillet L, Gourguechon C, Damaj G, Frenzel L, Meni C, Bouktit H, Collange AF, Gaudy-Marqueste C, Gousseff M, Le Mouel E, Hamidou M, Neel A, Ranta D, Jaussaud R, Guilpain P, Canioni D, Molina TJ, Bruneau J, Lhermitte L, Garcelon N, Javier RM, Pelletier F, Castelain F, Retornaz F, Cabrera Q, Zunic P, Gourin MP, Wierzbicka-Hainaut E, Viallard JF, Lavigne C, Hoarau C, Durieu I, Heiblig M, Dimicoli-Salazar S, Torregrosa-Diaz JM, Soria A, Arock M, Lortholary O, Bodemer C, Hermine O, and Rossignol J
- Subjects
- Humans, Retrospective Studies, Prevalence, Mast Cells pathology, Tryptases genetics, Mastocytosis, Systemic epidemiology, Mastocytosis, Systemic genetics, Mastocytosis, Systemic pathology, Mastocytosis epidemiology, Mastocytosis genetics, Mastocytosis pathology, Anaphylaxis pathology
- Abstract
Background: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal., Objective: We evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT., Methods: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases., Results: We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT
+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT- patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01)., Conclusion: Here we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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23. Salvage therapy with brentuximab-vedotin and bendamustine for patients with R/R PTCL: a retrospective study from the LYSA group.
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Aubrais R, Bouabdallah K, Chartier L, Herbaux C, Banos A, Brice P, Sibon D, Schiano JM, Cluzeau T, Laribi K, Le Calloch R, Bellal M, Delapierre B, Daguindau N, Amorim S, Agbetiafa K, Chauchet A, Besson C, Durot E, Bonnet C, Fouillet L, Bijou F, Tournilhac O, Gaulard P, Parrens MC, and Damaj G
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- Humans, Brentuximab Vedotin therapeutic use, Bendamustine Hydrochloride therapeutic use, Retrospective Studies, Salvage Therapy, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neoplasm Recurrence, Local drug therapy, Chronic Disease, Lymphoma, T-Cell, Peripheral drug therapy, Hodgkin Disease drug therapy
- Abstract
Patients with relapsed or refractory (R/R) peripheral T-cell lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and brentuximab-vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. This multicenter and retrospective study aimed to evaluate the efficacy and safety of the combination of BBv in patients with noncutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was the overall response rate. A total of 82 patients with R/R PTCL were included. The best overall response rate (ORR) was 68%, with 49% of patients in complete response (CR). In multivariable analysis, only the disease status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57%. Median duration of response was 15.4 months for patients in CR. With a median follow-up of 22 months, the median progression free survival (PFS) and overall survival (OS) were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 vs 4.8 months and not reached vs 12.4 months, respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events that were mainly hematologic. BBv is highly active in patients with R/R PTCL and should be considered as a one of the best options of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
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24. Successful allogeneic hematopoietic stem cell transplantation in a child with angioimmunoblastic T-cell lymphoma: A case report.
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Delehaye F, Deparis M, Buchbinder N, Bodet D, Minard V, Jean-Jacques B, Marie-Laure Q, Gaulard P, Sako N, Robe C, Bardet H, Damaj G, and Rouger J
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- Humans, Child, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Lymphoma, T-Cell, Peripheral therapy
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- 2023
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25. Prognostic relevance of sarcopenia, geriatric, and nutritional assessments in older patients with diffuse large B-cell lymphoma: results of a multicentric prospective cohort study.
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Pénichoux J, Lanic H, Thill C, Ménard AL, Camus V, Stamatoullas A, Lemasle E, Leprêtre S, Lenain P, Contentin N, Kraut-Tauzia J, Fruchart C, Kammoun L, Damaj G, Farge A, Delette C, Modzelewski R, Vaudaux S, Pépin LF, Tilly H, and Jardin F
- Subjects
- Humans, Aged, Prognosis, Nutrition Assessment, Prospective Studies, Postural Balance, Retrospective Studies, Time and Motion Studies, Sarcopenia, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
This prospective study aimed to investigate the prognostic effect of sarcopenia, geriatric, and nutritional status in older patients with diffuse large B-cell lymphoma (DLBCL). Ninety-five patients with DLBCL older than 70 years who were treated with immunochemotherapy were included. The lumbar L3 skeletal muscle index (L3-SMI) was measured by computed tomography at baseline, and sarcopenia was defined as low L3-SMI. Geriatric assessment included G8 score, CIRS-G scale, Timed Up and Go test, and instrumental activity of daily living. Nutritional status was assessed using the Mini Nutritional Assessment and the body mass index, and several scores used in the literature incorporating nutritional and inflammatory biomarkers, namely the Nutritional and inflammatory status (NIS), Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Glasgow Prognostic Score.Fifty-three patients were considered sarcopenic. Sarcopenic patients displayed higher levels of inflammation markers and lower levels of prealbumin than non-sarcopenic patients. Sarcopenia was associated with NIS, but was not associated with severe adverse events and treatment disruptions. They were, however, more frequent among patients with elevated NIS. Sarcopenia did not appear in this study as a prognostic factor for progression-free survival (PFS) or overall survival (OS). However, NIS emerged as predictive of the outcome with a 2-year PFS rate of 88% in the NIS ≤ 1 group and 49% in the NIS > 1 group and a significant effect in a multivariate analysis for both PFS (p = 0.049) and OS (HR = 9.61, CI 95% = [1.03-89.66], p = 0.04). Sarcopenia was not associated with adverse outcomes, but was related to NIS, which appeared to be an independent prognostic factor., (© 2023. The Author(s).)
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- 2023
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26. The Negative Influence of Baseline Cell-free DNA on Long-term Survival in DLBCL Depends on Frontline Treatment Intensity.
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Desmots F, Rossille D, Roussel M, Pangault C, Louarn L, De Saint Jore M, Le Gouill S, Bouabdallah K, Delwail V, Gressin R, Cornillon J, Damaj G, Maisonneuve H, Damotte D, Kraeber-Bodere F, Lamy T, Parrens MC, Milpied N, and Fest T
- Subjects
- Humans, Antibodies, Monoclonal, Murine-Derived therapeutic use, Disease-Free Survival, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Transplantation, Autologous, Rituximab therapeutic use, Vincristine, Doxorubicin, Cyclophosphamide, Hematopoietic Stem Cell Transplantation, Cell-Free Nucleic Acids, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Purpose: This study aims to investigate the relationship between the intensity of the initial treatment given to patients with de novo diffuse large B-cell lymphoma (DLBCL) and the impact of their baseline cell-free DNA (cfDNA) levels on their long-term survival., Experimental Design: The GOELAMS 075 randomized clinical trial compared rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with high-dose R-chemotherapy plus autologous stem cell transplantation (R-HDT) for patients aged ≤60. An interim PET assessment was used to refer patients for salvage therapy. With a median follow-up of more than 5.8 years, we analyzed the effects of the treatment arm, salvage therapy, and cfDNA level at diagnosis on overall survival (OS)., Results: In a representative group of 123 patients, a high cfDNA concentration (>55 ng/mL) at diagnosis was associated with poor clinical prognostic factors and constituted a prognostic marker, independently of the age-adjusted International Prognostic Index. A cfDNA level above a threshold value of 55 ng/mL at diagnosis was associated with significantly worse OS. In an intention-to-treat analysis, high-cfDNA R-CHOP patients (but not high-cfDNA R-HDT patients) had worse OS [HR (95% confidence interval), 3.99 (1.98-10.74); P = 0.006]. In patients with high cfDNA levels, salvage therapy and transplantation were associated with a significantly higher OS rate. Among 50 patients with complete response 6 months after the end of treatment, for 11 of 24 R-CHOP patients, the cfDNA did not fall back to normal values., Conclusions: In this randomized clinical trial, intensive regimens mitigated the negative influence of high cfDNA levels in de novo DLBCL, relative to R-CHOP., (©2023 American Association for Cancer Research.)
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- 2023
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27. ALK-negative anaplastic large cell lymphoma with DUSP22 rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study.
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Sibon D, Bisig B, Bonnet C, Poullot E, Bachy E, Cavalieri D, Fataccioli V, Bregnard C, Drieux F, Bruneau J, Lemonnier F, Dupuy A, Bossard C, Parrens M, Bouabdallah K, Ketterer N, Berthod G, Cairoli A, Damaj G, Tournilhac O, Jais JP, Gaulard P, and De Leval L
- Subjects
- Humans, Anaplastic Lymphoma Kinase genetics, Brentuximab Vedotin therapeutic use, Disease-Free Survival, In Situ Hybridization, Fluorescence, Receptor Protein-Tyrosine Kinases genetics, Lymphoma, Large-Cell, Anaplastic diagnosis, Lymphoma, Large-Cell, Anaplastic drug therapy, Lymphoma, Large-Cell, Anaplastic genetics
- Abstract
ALK-negative anaplastic large cell lymphoma (ALCL) comprises subgroups harboring rearrangements of DUSP22 (DUSP22- R) or TP63 (TP63-R). Two studies reported 90% and 40% 5-year overall survival (OS) rates in 21 and 12 DUSP22-R/TP63- not rearranged (NR) patients, respectively, making the prognostic impact of DUSP22-R unclear. Here, 104 newly diagnosed ALK-negative ALCL patients (including 37 from first-line clinical trials) from the LYSA TENOMIC database were analyzed by break-apart fluorescence in situ hybridization assays for DUSP22-R and TP63-R. There were 47/104 (45%) DUSP22-R and 2/93 (2%) TP63-R cases, including one DUSP22-R/TP63-R case. DUSP22-R tumors more frequently showed CD3 expression (62% vs. 35%, P=0.01), and less commonly a cytotoxic phenotype (27% vs. 82%; P<0.001). At diagnosis, DUSP22- R ALCL patients more frequently had bone involvement (32% vs. 13%, P=0.03). The patient with DUSP22-R/TP63-R ALCL had a rapidly fatal outcome. After a median follow-up of 4.9 years, 5-year progression-free survival (PFS) and OS rates of 84 patients without TP63-R treated with curative-intent anthracycline-based chemotherapy were 41% and 53%, respectively. According to DUSP22 status, 5-year PFS was 57% for 39 DUSP22-R versus 26% for 45 triple-negative (DUSP22-NR/TP63-NR/ALK-negative) patients (P=0.001). The corresponding 5-year OS rates were 65% and 41%, respectively (P=0.07). In multivariate analysis, performance status and DUSP22 status significantly affected PFS, and distinguished four risk groups, with 4-year PFS and OS ranging from 17% to 73% and 21% to 77%, respectively. Performance status but not DUSP22 status influenced OS. The use of brentuximab vedotin in relapsed/refractory patients improved OS independently of DUSP22 status. Our findings support the biological and clinical distinctiveness of DUSP22- R ALK-negative ALCL. Its relevance to outcome in patients receiving frontline brentuximab vedotin remains to be determined.
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- 2023
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28. Efficacy of a short sandwich protocol, methotrexate, gemcitabine, L-asparaginase and dexamethasone chemotherapy combined with radiotherapy, in localised newly diagnosed NK/T-cell lymphoma: A French retrospective study.
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Chaubard S, Marouf A, Lavergne D, Lemonnier F, Rossignol J, Clavert A, Gressin R, Cartron G, Waultier-Rascalou A, Vargaftig J, Salles G, Bachy E, Ghesquières H, Tournilhac O, Chauchet A, Le Gouill S, Damaj G, Fornecker LM, Sibon D, Obéric L, Michot JM, Gaulard P, Hermine O, Couronné L, and Jaccard A
- Subjects
- Humans, Asparaginase, Methotrexate, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neoplasm Recurrence, Local drug therapy, Treatment Outcome, Dexamethasone, Multicenter Studies as Topic, Gemcitabine, Lymphoma, Extranodal NK-T-Cell drug therapy, Lymphoma, Extranodal NK-T-Cell radiotherapy
- Abstract
Extranodal NK/T-cell lymphoma, nasal type is a rare and aggressive form of lymphoma, historically associated with poor prognosis. We report here the results of a retrospective multi-centre study evaluating the efficacy of MGAD (methotrexate, gemcitabine, L-asparaginase and dexamethasone) regimen (two cycles) combined with 'sandwich' radiotherapy in 35 patients with localised newly diagnosed extranodal NK/T-cell lymphoma. Thirty-two patients (91%) reached complete remission. With a long median follow-up of 59.6 months, progression-free and overall survival at 2 and 5 years were 71%, 80% and 53%, 73%, respectively. Around one third of the patients experienced relapse within a median time of 14.5 months. Side-effects were manageable with grades 3-4 cytopenias, mucositis and infection in 50%, 24% and 21% of the cases, respectively. Monitoring of asparaginase activity was performed in 13 patients and showed inactivation of the drug in seven (54%) patients. Our results indicate that a short therapy by sandwich MGAD chemoradiotherapy is a tolerable and effective treatment option in localised newly diagnosed extranodal NK/T-cell lymphoma patients., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2023
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29. Role of social status and social environment on net survival in patients with chronic lymphocytic leukemia: A high-resolution population-based study.
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Delapierre B, Troussard X, Damaj G, Dejardin O, and Tron L
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- Humans, Social Status, Prognosis, Proportional Hazards Models, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Hematologic Neoplasms
- Abstract
Background: The prognostic roles of social status and social environment in chronic lymphocytic leukemia have been highlighted in some solid tumors but remain unclear in hematological malignancies. The objective of this study was to evaluate the influence of individual social status (with socioprofessional category, SPC) and social environment (with European deprivation index, EDI) on net survival in a high-resolution population with CLL., Methods: We included CLL patients from the Regional Register of Hematological Malignancies in Normandy belonging to the French Network of Cancer Registries (Francim). The SPC variable was divided into 5 categories: farmers, craftsmen, higher employment, intermediate employment, and workers/employees. Net survival was used to estimate the excess of mortality in CLL independent of other possible causes of death using French life tables. Net survival was estimated with a nonparametric method (Pohar-Perme) and with a flexible excess mortality hazard model. Missing data were handled with multiple imputation., Results: A total of 780 patients were included. The median follow-up was 7.9 years. The crude survival at 10 years was 50%, and the net survival at 10 years was 80%. In multivariate analysis, a higher age (EHR: 1.04 [1.01-1.07]), being a craftsman (EHR
craftsmen/higher.employment : 4.15 [0.86-20.15]), being a worker or an employee (EHRworkers.employees/higher.employment : 3.57 [1.19-10.7]), having a Binet staging of B or C (EHR: 3.43 [1.84-6.42]) and having a lymphocyte count > 15 G/L (EHR: 3.80 [2.17-6.65]) were statistically associated with a higher risk of excess mortality. EDI was not associated with excess mortality (EHR: 0.97 [0.90-1.04])., Conclusion: Socioprofessional category was a prognostic factor for an excess of mortality in CLL. Craftsmen and workers/employees shared a worse prognosis than workers with higher employment. The social environment was not a prognostic factor. Further work should be performed to explore causal epidemiologic or biological factors and other hematological malignancies., Competing Interests: Declaration of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2023
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30. Isolated intraocular relapses of primary cerebral lymphomas: An LOC network study.
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Younan N, Soussain C, Choquet S, Cassoux N, Touitou V, Schmitt A, Chinot O, Oberic L, Damaj G, Houot R, Ghesquières H, Laribi K, Ahle G, Taillandier L, Paillassa J, Gyan E, Jardin F, Delwail V, Marolleau JP, Tempescul A, Agapé P, Bourniquel M, Vacheret F, Jdid I, Le Garff-Tavernier M, Malaise D, Alentorn A, Xuan KH, and Houillier C
- Subjects
- Humans, Aged, Transplantation, Autologous, Retrospective Studies, Vitreous Body, Hematopoietic Stem Cell Transplantation, Retinal Neoplasms, Lymphoma
- Abstract
Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68 years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69 months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p < 0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1 months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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31. Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study.
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Houillier C, Dureau S, Taillandier L, Houot R, Chinot O, Moluçon-Chabrot C, Schmitt A, Gressin R, Choquet S, Damaj G, Peyrade F, Abraham J, Delwail V, Gyan E, Sanhes L, Cornillon J, Garidi R, Delmer A, Al Jijakli A, Morel P, Waultier A, Paillassa J, Chauchet A, Gastinne T, Laadhari M, Plissonnier AS, Feuvret L, Cassoux N, Touitou V, Ricard D, Hoang-Xuan K, and Soussain C
- Subjects
- Humans, Middle Aged, Adolescent, Young Adult, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neoplasm Recurrence, Local drug therapy, Transplantation, Autologous, Combined Modality Therapy, Central Nervous System Neoplasms pathology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Lymphoma radiotherapy, Lymphoma drug therapy
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported the results of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma (age 18-60 years). Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). The median follow-up was 33 months. In this report, we provide long-term data (median follow-up, 8 years) regarding the outcomes and toxicities. Fifty-three and 44 patients received induction chemotherapy followed by WBRT or ASCT, respectively. Their 8-year event-free survival from random assignment was 67% and 39% in the ASCT and WBRT arms, respectively ( P = .03), with a significantly lower risk of relapse after ASCT (hazard ratio, 0.13; P < .001). One third of patients who relapsed after WBRT were alive after salvage treatment. Five and four patients died of ASCT and WBRT-related toxicities, respectively. The 8-year overall survival was 69% and 65% in the ASCT and WBRT arms, respectively (not significant). Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses.
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- 2022
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32. Reduced-dose WBRT as consolidation treatment for patients with primary CNS lymphoma: an LOC network study.
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Lesueur P, Damaj G, Hoang-Xuan K, Roland V, Schmitt A, Chinot O, Fabbro M, Agapé P, Moluçon-Chabrot C, Chebrek S, Alentorn A, Feuvret L, Delgadillo D, Stefan D, Choquet S, Nichelli L, Mokhtari K, Mathon B, Dureau S, Soussain C, and Houillier C
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Humans, Middle Aged, Neoplasm Recurrence, Local drug therapy, Prospective Studies, Retrospective Studies, Transplantation, Autologous, Central Nervous System Neoplasms drug therapy, Hematopoietic Stem Cell Transplantation, Lymphoma, Non-Hodgkin therapy
- Abstract
The optimal consolidation strategy for primary central nervous system lymphoma (PCNSL) remains controversial. Preventing radio-induced neurotoxicity of consolidation treatment through reduced-dose whole-brain radiotherapy (rdWBRT) at a dose of 23.4 Gy is an interesting alternative to conventional WBRT in patients aged <60 years. From the LOC Network (Network for Oculo-cerebral Lymphomas) database, we retrospectively selected patients with PCNSL aged <60 years who showed complete (CR) or unconfirmed CR after high-dose methotrexate-based chemotherapy and had received consolidation rdWBRT as the first-line treatment. If available, prospective neuropsychological follow-ups were reported. Twenty-nine patients diagnosed between 2013 and 2018 met the study selection criteria. Nine (31%) patients experienced relapse during the follow-up, with a median time from radiotherapy to recurrence of 8.7 months (interquartile range, 4-11.5). Five of those patients received salvage treatment and consolidation with intensive chemotherapy and autologous stem cell transplantation. Progression-free survival rates were 89% (95% confidence interval [CI] 79%-100%), 72% (95% CI, 56%-88%), and 69% (95% CI, 52%-85%) at 1, 2, and 5 years, respectively. Overall survival rates were 100%, 89% (95% CI, 79%-100%), and 86% (95% CI, 74%-99%) at 1, 2, and 5 years, respectively, and were consistent with those observed for standard-dose WBRT (sdWBRT). No prognostic factor was identified. The results of the 36-month neuropsychological follow-up for a subset of patients appeared reassuring, with most patients exhibiting maintenance of or improvements in their baseline conditions. Our results, combined with phase 2 study results, support the use of rdWBRT instead of sdWBRT as a consolidation treatment in <60-year-old patients showing CR after induction treatment., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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33. Low total gamma globulin level discovery at diffuse large B-cell lymphoma diagnosis predicts high risk of infection-related death: data from a monocentric retrospective study.
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Nguyen A, Martin-Silva N, de Boysson H, Deshayes S, Gac AC, Reboursière E, Damaj G, and Aouba A
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- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Retrospective Studies, gamma-Globulins therapeutic use, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Objective: Diffuse large B-cell lymphoma can complicate the course of B-cell primary immunodeficiencies or induce lowering of total gamma globulin levels, whose clinical status as an effective secondary immunodeficiency remains unspecified. This study aimed to assess the frequency, and clinical and prognostic relevance of the low total gamma-globulin levels discovered at diagnosis of diffuse large B-cell lymphoma., Results: In a 2-year monocentric retrospective study, 96 patients diagnosed with diffuse large B-cell lymphoma who had a serum electrophoresis were included. Patients were divided into those with lower (L-TGL and higher (H-TGL) total gamma-globulin levels (total gamma-globulin levels ≤5.5 g/l and >5.5 g/l) and compared for outcomes, including fatal infectious events. Twelve (12.5%; 8 males; age median 68 years, range 55-82 years) exhibited L-TGL. There was no difference between the both groups regarding demographics, Ann Arbor lymphoma stage, inflammatory parameters or chemotherapy regimen. However, overall death rates (10/12, 83.3% versus 22/96, 26.2%; p = 0.03) and infection-related death rates (10/12, 83% versus 6/96, 6.2%; p <0.001) were significantly higher in the L-TGL group., Conclusion: We demonstrate for the first time the strong negative impact of L-TGL on overall and infection-related mortality in diffuse large B-cell lymphoma. Prospective studies should distinguish immunodeficiencies secondary to the lymphoma from pre-existing humoral primary immunodeficiencies, using biomolecular testing and post-treatment total gamma-globulin level monitoring, to determine the best management strategy for infectious risk during diffuse large B-cell lymphoma treatment in the context of L-TGL.
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- 2022
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34. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life-experience of the French Network.
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Schenone L, Houillier C, Tanguy ML, Choquet S, Agbetiafa K, Ghesquières H, Damaj G, Schmitt A, Bouabdallah K, Ahle G, Gressin R, Cornillon J, Houot R, Marolleau JP, Fornecker LM, Chinot O, Peyrade F, Bouabdallah R, Moluçon-Chabrot C, Gyan E, Chauchet A, Casasnovas O, Oberic L, Delwail V, Abraham J, Roland V, Waultier-Rascalou A, Willems L, Morschhauser F, Fabbro M, Ursu R, Thieblemont C, Jardin F, Tempescul A, Malaise D, Touitou V, Nichelli L, Le Garff-Tavernier M, Plessier A, Bourget P, Bonmati C, Wantz-Mézières S, Giordan Q, Dorvaux V, Charron C, Jabeur W, Hoang-Xuan K, Taillandier L, and Soussain C
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Busulfan, Carmustine therapeutic use, Central Nervous System pathology, Cyclophosphamide therapeutic use, Etoposide, Humans, Neoplasm Recurrence, Local drug therapy, Prospective Studies, Thiotepa, Transplantation, Autologous, Treatment Outcome, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms pathology, Hematopoietic Stem Cell Transplantation adverse effects, Lymphoma drug therapy
- Abstract
We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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35. Effective Anti-SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders.
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Rossignol J, Ouedrani A, Livideanu CB, Barete S, Terriou L, Launay D, Lemal R, Greco C, Frenzel L, Meni C, Bodemere-Skandalis C, Polivka L, Collange AF, Hachichi H, Bouzourine S, Messaoud DN, Negretto M, Vendrame L, Jambou M, Gousseff M, Durupt S, Lega JC, Durand JM, Gaudy C, Damaj G, Gourin MP, Hamidou M, Bouillet L, Le Mouel E, Maria A, Zunic P, Cabrera Q, Vincent D, Lavigne C, Riviere E, Gourguechon C, Courbebaisse M, Lebeaux D, Parfait B, Friedlander G, Brignier A, Lhermitte L, Molina TJ, Bruneau J, Agopian J, Dubreuil P, Ranta D, Mania A, Arock M, Staropoli I, Tournilhac O, Lortholary O, Schwartz O, Chatenoud L, and Hermine O
- Subjects
- Antibodies, Viral, Humans, Immunity, Mast Cells, SARS-CoV-2, COVID-19, Mastocytosis
- Abstract
Background: Mast cells are key players in innate immunity and the T
H 2 adaptive immune response. The latter counterbalances the TH 1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published., Objective: To study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting., Methods: Clinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti-SARS-CoV-2-specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies., Results: Overall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2-specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2-specific, IFN-γ-producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden)., Conclusions: Patients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ., (Copyright © 2022. Published by Elsevier Inc.)- Published
- 2022
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36. Bendamustine-EAM versus R-BEAM after high-dose cytarabine-based induction in newly diagnosed patients with mantle cell lymphoma, a LYSA retrospective study.
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Costes-Tertrais D, Hueso T, Gastinne T, Thieblemont C, Oberic L, Bouabdallah K, Garciaz S, Tchernonog E, Dartigeas C, Ribrag V, Fogarty P, Casasnovas RO, Houot R, Delette C, Malak S, Fornecker LM, Gressin R, Damaj G, and Le Gouill S
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bendamustine Hydrochloride therapeutic use, Carmustine pharmacology, Carmustine therapeutic use, Cytarabine therapeutic use, Etoposide, Humans, Melphalan therapeutic use, Retrospective Studies, Transplantation, Autologous methods, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell drug therapy
- Abstract
Cytarabine-based immuno-chemotherapy followed by autologous stem cell transplantation (ASCT) consolidation is standard of care for fit patients with Mantle Cell Lymphoma (MCL). BEAM (Carmustine, Etoposide, Aracytine, Melphalan) is among the most frequently used conditioning regimen. Studies comparing BEAM with Bendamustine-EAM (BeEAM) have suggested that patients treated with BeEAM have a better progression-free survival (PFS). We performed a cross-study analysis to better evaluate BeEAM. Thirty-five patients from a retrospective study who received R-DHAP/BeEAM were compared to 245 patients from the LyMa trial (NCT00921414) who all received R-DHAP followed by R-BEAM. PFS and Overall Survival (OS) were estimated using Kaplan-Meier methods. At 2 years there was no difference between R-BEAM and BeEAM in either PFS (84.9% versus 87.9%; p = 0.95) or OS (91.8% versus 94.2%; p = 0.30). Analyses were repeated on a propensity score to reduce biases. Each patient from the BeEAM cohort (n = 30) was matched to three patients from the R-BEAM cohort (n = 90) for age, sex, MIPI score, pre-transplant status disease and rituximab maintenance (RM). PFS and OS at 2 years remained similar between R-BEAM and BeEAM with more renal toxicity in BeEAM group. MCL patients who received R-DHAP induction before ASCT have similar outcome after R-BEAM or BeEAM conditioning regimen., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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37. Immunophenotypic Analysis of Hairy Cell Leukemia (HCL) and Hairy Cell Leukemia-like (HCL-like) Disorders.
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Maitre E, Cornet E, Salaün V, Kerneves P, Chèze S, Repesse Y, Damaj G, and Troussard X
- Abstract
Hairy cell leukemia (HCL) is characterized by abnormal villous lymphoid cells that express CD103, CD123, CD25 and CD11c. HCL-like disorders, including hairy cell leukemia variant (vHCL) and splenic diffuse red pulp lymphoma (SDRPL), have similar morphologic criteria and a distinct phenotypic and genetic profile. We investigated the immunophenotypic features of a large cohort of 82 patients: 68 classical HCL, 5 vHCL/SDRPL and 9 HCL-like NOS. The HCL immunophenotype was heterogeneous: positive CD5 expression in 7/68 (10%), CD10 in 12/68 (18%), CD38 in 24/67 (36%), CD23 in 22/68 (32%) and CD43 in 19/65 (31%) patients. CD26 was expressed in 35/36 (97%) of HCL patients, none of vHCL/SDRPL and one of seven HCL-like NOS (14%). When adding CD26 to the immunologic HCL scoring system (one point for CD103, CD123, CD25, CD11c and CD26), the specificity was improved, increasing from 78.6% to 100%. We used unsupervised analysis of flow cytometry raw data (median fluorescence, percentage of expression) and the mutational profile of BRAF, MAP2K1 and KLF2 . The analysis showed good separation between HCL and vHCL/SDRPL. The HCL score is not sufficient, and the use of unsupervised analysis could be promising to achieve a distinction between HCL and HCL-like disorders. However, these preliminary results have to be confirmed in a further study with a higher number of patients.
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- 2022
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38. Correction to: Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party.
- Author
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Schetelig J, Chevallier P, van Gelder M, Hoek J, Hermine O, Chakraverty R, Browne P, Milpied N, Malagola M, Socié G, Delgado J, Deconinck E, Damaj G, Maury S, Beelen D, Quoc SN, Shankara P, Brecht A, Mayer J, Hunault-Berger M, Bittenbring J, Thieblemont C, Lepretre S, Baldauf H, de Wreede LC, Tournilhac O, Yakoub-Agha I, Kröger N, and Dreger P
- Published
- 2022
- Full Text
- View/download PDF
39. Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA).
- Author
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Bachy E, Camus V, Thieblemont C, Sibon D, Casasnovas RO, Ysebaert L, Damaj G, Guidez S, Pica GM, Kim WS, Lim ST, André M, García-Sancho AM, Penarrubia MJ, Staber PB, Trotman J, Hüttmann A, Stefoni V, Re A, Gaulard P, Delfau-Larue MH, de Leval L, Meignan M, Li J, Morschhauser F, and Delarue R
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Asia, Australia, Cyclophosphamide adverse effects, Cyclophosphamide therapeutic use, Depsipeptides adverse effects, Disease Progression, Doxorubicin adverse effects, Doxorubicin therapeutic use, Europe, Female, Histone Deacetylase Inhibitors adverse effects, Humans, Lymphoma, T-Cell, Peripheral mortality, Lymphoma, T-Cell, Peripheral pathology, Male, Middle Aged, Prednisone adverse effects, Prednisone therapeutic use, Progression-Free Survival, Time Factors, Vincristine adverse effects, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Depsipeptides therapeutic use, Histone Deacetylase Inhibitors therapeutic use, Lymphoma, T-Cell, Peripheral drug therapy
- Abstract
Purpose: Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study showed the feasibility of combining romidepsin with CHOP (Ro-CHOP)., Methods: This study is a randomized phase III study of Ro-CHOP versus CHOP in adult patients with previously untreated PTCL. All patients received CHOP in 3-week cycles for six cycles. Romidepsin, 12 mg/m
2 , was administered intravenously over a 4-hour period on days 1 and 8 of each 3-week cycle for six cycles. The primary end point was progression-free survival (PFS) according to International Working Group 1999 criteria., Results: Between January 2013 and December 2017, 421 patients were enrolled (Ro-CHOP, n = 211; CHOP, n = 210). The median PFS for Ro-CHOP versus CHOP was 12.0 months (95% CI, 9.0 to 25.8) versus 10.2 months (95% CI, 7.4 to 13.2) with a hazard ratio of 0.81 ( P = .096). In the Ro-CHOP versus CHOP arms, the median overall survival was 51.8 versus 42.9 months and the objective response rate was 63% versus 60% with complete response plus unconfirmed complete response rates of 41% versus 37% ( P > .1 in all comparisons), respectively. Grade 3 or 4 treatment-emergent adverse events occurring in ≥ 30% of patients in the Ro-CHOP arm included thrombocytopenia (50% v 10% in the Ro-CHOP v CHOP arms, respectively), neutropenia (49% v 33%), anemia (47% v 17%), and leukopenia (32% v 20%)., Conclusion: The addition of romidepsin to CHOP did not improve PFS, response rates, nor overall survival and increased the frequency for grade ≥ 3 treatment-emergent adverse events. Ro-CHOP does not represent a significant advance in the standard of care for patients with previously untreated PTCL., Competing Interests: Emmanuel BachyHonoraria: Gilead Sciences, Roche, Amgen, Janssen-CilagConsulting or Advisory Role: Roche, Gilead Sciences, Incyte, TakedaResearch Funding: Amgen Foundation (Inst)Travel, Accommodations, Expenses: Janssen-Cilag, Roche, Gilead Sciences, Incyte Vincent CamusHonoraria: Roche/Genentech, Incyte, Janssen, Gilead Sciences, NovartisConsulting or Advisory Role: RocheResearch Funding: iQone Healthcare (Inst)Travel, Accommodations, Expenses: Pfizer, Roche Catherine ThieblemontHonoraria: Celgene, AbbVie, Bayer, Janssen, Roche, Incyte, Novartis, Gilead SciencesResearch Funding: RocheTravel, Accommodations, Expenses: Roche, Janssen-Cilag, Kite/Gilead, Novartis David SibonConsulting or Advisory Role: Takeda, iQone Healthcare, Janssen, Roche, AbbVieTravel, Accommodations, Expenses: Takeda, Janssen René-Olivier CasasnovasHonoraria: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, AmgenConsulting or Advisory Role: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, IncyteResearch Funding: Roche/Genentech (Inst), Gilead Sciences (Inst), Takeda (Inst)Travel, Accommodations, Expenses: Roche/Genentech, Takeda, Gilead Sciences, Janssen Loïc YsebaertHonoraria: AbbVieConsulting or Advisory Role: AbbVie, Janssen-Cilag, Roche, Gilead SciencesResearch Funding: Roche (Inst), Janssen-Cilag (Inst), Gilead Sciences (Inst) Gandhi DamajConsulting or Advisory Role: Roche/Genentech, Takeda, iQoneResearch Funding: TakedaTravel, Accommodations, Expenses: PFIZEE, Roche/Genentech, AbbVie Stéphanie GuidezConsulting or Advisory Role: Kite/GileadTravel, Accommodations, Expenses: Janssen Marc AndréConsulting or Advisory Role: Takeda, BMSiResearch Funding: Takeda (Inst), Roche (Inst)Travel, Accommodations, Expenses: Roche, Celgene, Gilead Sciences Alejandro Martín García-SanchoHonoraria: Roche, Janssen-Cilag, Celgene, Servier, Gilead Sciences, TakedaConsulting or Advisory Role: Roche, Celgene, MorphoSys, Kyowa Hakko Kirin, iQone, EUSA Pharma, Gilead Sciences, Novartis, Servier, IncyteExpert Testimony: Gilead SciencesTravel, Accommodations, Expenses: Roche, Celgene¸ Servier Maria Jesus PenarrubiaHonoraria: AbbVie, Celgene, Servier, Takeda, RocheConsulting or Advisory Role: Gilead Sciences, Novartis, Celgene, AbbVie, Takeda, Clinigen GroupResearch Funding: CelgeneTravel, Accommodations, Expenses: Amgen, Servier, Novartis, Janssen, Celgene, Takeda Philipp B. StaberHonoraria: Roche, Amgen, Takeda, Abbott/AbbVie, Janssen Oncology, Incyte, Celgene, Bristol Myers Squibb/Pfizer, MSD Oncology, AstraZenecaResearch Funding: Roche (Inst) Judith TrotmanResearch Funding: BeiGene (Inst), Roche/Genentech (Inst), Pharmacyclics (Inst), Janssen-Cilag (Inst), Takeda (Inst), Celgene (Inst)Travel, Accommodations, Expenses: Roche/Genentech Andreas HüttmannHonoraria: TakedaConsulting or Advisory Role: TakedaTravel, Accommodations, Expenses: Roche Pharma AG Philippe GaulardHonoraria: Takeda, Gilead SciencesConsulting or Advisory Role: TakedaResearch Funding: Takeda (Inst), Innate Pharma (Inst), Sanofi (Inst)Travel, Accommodations, Expenses: Roche Marie-Helene Delfau-LarueHonoraria: Gilead Sciences, AmgenResearch Funding: Roche, CelgeneTravel, Accommodations, Expenses: Mundipharma Laurence de LevalHonoraria: Novartis (Inst)Consulting or Advisory Role: Lunaphore Technologies (Inst), Bayer (Inst) Michel MeignanHonoraria: RocheTravel, Accommodations, Expenses: Roche Ju LiEmployment: Bristol Myers Squibb/CelgeneStock and Other Ownership Interests: Bristol Myers Squibb/CelgeneResearch Funding: Bristol Myers Squibb/CelgeneTravel, Accommodations, Expenses: Bristol Myers Squibb/Celgene Franck MorschhauserConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Celgene, Bristol Myers Squibb, AbbVie, Epizyme, ServierSpeakers' Bureau: RocheExpert Testimony: Roche/Genentech Richard DelarueEmployment: Celgene/Bristol Myers Squibb, BeiGeneStock and Other Ownership Interests: Celgene/Bristol Myers Squibb, BeiGeneNo other potential conflicts of interest were reported.- Published
- 2022
- Full Text
- View/download PDF
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