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Florence Broussais-Guillaumot,
Diane Coso,
Nawel Belmecheri,
Vadim Ivanov,
Jean-Marc Schiano,
Thérèse Aurran-Schleinitz,
Anne-Marie Stoppa,
Bruno Chetaille,
Luc Xerri,
Benjamin Esterni,
Didier Blaise, Reda Bouabdallah
[show abstract]
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ABSTRACT: Condensed abstract Prognosis of peripheral T cell lymphoma is poor despite the use of bone marrow transplantation. Some new drugs offer real hope. There are no funding sources for the manuscript. Background: Peripheral T-cell lymphomas are characterized by a poor clinical outcome. Design and Methods: We retrospectively analyzed 208 adults treated in our institution between 2000 and 2011. Results: Median age at diagnosis was 55. Fifty-one percent had B symptoms and 51% serum elevated LDH levels. ECOG was 0-1 in 63% and 2-4 in 37%. According to Ann Arbor classification, 16% were at stage I-II and 84% at stage III-IV. The histological subtypes were: 39% of peripheral T-cell NHL unspecified (PTCL-U), and 19.5% anaplastic large cell lymphoma (ALCL), with 9.5% ALK+ and 10% ALK-, 25% of angio-immunoblastic lymphoma (AILT). Primary extranodal lymphoma represented 17% and 8% were diagnosed with hemophagocytosis. Induction chemotherapy was CHOP in 87% of patients. The median number of chemotherapy was 2 (1-7). A complete response was obtained for 57% of the patients. Among them, 32% had ASCT and 10% allogenic SCT, while 38 % were primary refractory. Five-year overall survival (OS) was 28.5% (22.3-36.3), and five year event-free survival (EFS) was 18.4 % (13.4-25.3). A multivariate analysis showed that ALCL-ALK+ (p=0.008), AILT (p<0.001), extranodal involvement (p=0.005), PS>1 (p<0.016), LDH>N (p=0.003), and hemophagocytosis (p=0.001) are independent adverse factors for OS. Conclusion: Conventional chemotherapy with intensive treatment is not sufficient to improve response rate. Optimal management is required.
Leukemia & lymphoma 02/2013; · 2.40 Impact Factor
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Jean El-Cheikh,
Roberto Crocchiolo,
Sabine Furst,
Anne-Marie Stoppa,
Patrick Ladaique,
Catherine Faucher,
Boris Calmels,
Claude Lemarie,
Jean-Marc Schiano De Colella,
Angela Granata,
Diane Coso, Reda Bouabdallah,
Christian Chabannon,
Didier Blaise
[show abstract]
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ABSTRACT: This study examines the long-term outcomes of a cohort of patients with myeloma who were treated with reduced-intensity conditioning (RIC) regimens after a minimum follow-up of 5 years at our centre. A total of 53 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem-cell transplantation (Allo-SCT) between January 2000 and January 2007 were identified. The median follow-up of living patients was 84 months (51-141). The median age of the MM patients was 50 (28-70) years. Fifty-one patients (96%) received a transplant from a sibling donor. The median time between diagnosis and Allo-SCT was 34 months (6-161), and the median time between auto-SCT and Allo-SCT was 10 months (1-89). Fifty-one patients (96%) received at least one auto-SCT; 24 patients (45%) received a tandem auto-Allo-SCT. At last follow-up, 21 patients (40%) are alive > 5 years post RIC Allo-SCT. At last follow-up, 14 (26%) are in first complete remission (CR), and four patients (8%) in second CR after donor lymphocyte infusion or re-induction with one of the new anti-myeloma drugs (bortezomib or lenalidomide) after Allo-SCT. Eight patients (38%) among these long survivors received one of these new drugs as induction or relapse treatment before Allo-SCT. Disease status and occurrence of cGvHD were significantly associated with progression-free survival (PFS); hazard ratio (HR) = 0.62 (0.30-1.29, P = 0.20). Acute GvHD was correlated with higher transplant-related mortality; HR = 4.19 (1.05-16.77, P = 0.04). No variables were associated with overall survival (OS). In conclusion, we observe that long-term disease control can be expected in a subset of MM patients undergoing RIC Allo-SCT. After 10 years, the OS and PFS were 32% and 24%, respectively. The PFS curve after Allo-SCT stabilizes in time with a plateau after 6 years post Allo-SCT. Am. J. Hematol. 00:000-000, 2013. © 2013 Wiley Periodicals, Inc.
American Journal of Hematology 02/2013; · 4.67 Impact Factor
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Jean El-Cheikh,
Raynier Devillier,
Roberto Crocchiolo,
Sabine Fürst,
Boris Calmels,
Catherine Faucher,
Anne Marie Stoppa,
Angela Granata,
Luca Castagna,
Patrick Ladaique,
Claude Lemarie, Reda Bouabdallah,
Christine Zandotti,
Michele Merlin,
Pierre Berger,
Christian Chabannon,
Didier Blaise
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ABSTRACT: Scope of the study was to investigate the impact of pre-transplant CMV serostatus of the donor and/or recipient on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer center at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R] -) 17 patients (17.1%), intermediate risk (D+/R) 14 patients (14.1%), or high risk - either (D-/R+) 31 patients (31.3%) or (D+/R+), 37 patients (37.3%). Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26-318). Three patients (3%) developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs. intermediate: 29% vs. high: 50%; p=0.001) and the presence of grade II-IV acute GvHD (Hazard Ratio: HR=2.1 [1.1-3.9]). Thirty-six of the 39 patients (92%) with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II-IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM) were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005). Two-year overall and progression free survival were 56% and 34%, respectively. Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre-emptive treatment strategy could in part explain these results. Novel prophylactic measures such as immunotherapy and drug prophylaxis need to be considered in this group of patients, warranting further prospective studies.
Mediterranean Journal of Hematology and Infectious Diseases 01/2013; 5(1):e2013026.
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Vincent Ribrag,
Hervé Tilly,
Olivier Casasnovas,
André Bosly, Reda Bouabdallah,
Richard Delarue,
François Boue,
Dominique Bron,
Pierre Feugier,
Corinne Haioun,
Firtz Offner,
Bertrand Coiffier
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ABSTRACT: PURPOSE: Bortezomib has previously demonstrated activity in indolent lymphomas including follicular lymphoma with response rate ranging from 13% to 56%. However, the optimal schedule of bortezomib remains to be investigated in follicular lymphoma. EXPERIMENTAL DESIGN: We conducted a randomised phase II study where patients with follicular lymphoma in relapse or refractory receive either bortezomib 1.5mg/m(2) biweekly on days 1, 4, 8 and 11 of a 21-day cycle (arm A) or 1.6mg/m(2) weekly on days 1, 8, 15 and 22 of a 35-day cycle (arm B). An interim analysis was planned after 15 fully evaluable patients randomised in each treatment arm. If only five subjects or fewer respond, the treatment arm was concluded to be ineffective and was closed to inclusion. RESULTS: Eighty-seven patients were included in the trial. Arm B was closed to inclusion after interim analysis. 15/50 patients (30%) in arm A and 8/37 patients (22%) in arm B achieved a response. Median duration of response was 16 and 15 months for arms A and B, respectively. Most drug-related adverse events (AEs) (all grades, all cycles) were mild. CONCLUSION: This study demonstrates tolerability and durable clinical benefit of bortezomib when given at 1.5mg/m(2) biweekly. Despite a higher response rate in the biweekly arm, no major difference in patient's outcome was observed between the two arms in the final analysis.
European journal of cancer (Oxford, England: 1990) 12/2012; · 4.12 Impact Factor
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Jean El-Cheikh,
Roberto Crocchiolo,
Sabine Furst,
Patrick Ladaique,
Luca Castagna,
Catherine Faucher,
Boris Calmels,
Claire Oudin,
Claude Lemarie,
Angela Granata,
Raynier Devillier,
Norbert Vey, Reda Bouabdallah,
Christian Chabannon,
Didier Blaise
[show abstract]
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ABSTRACT: Donor lymphocyte infusions (DLI) can induce remission in patients with hematologic malignancies who relapse after allogeneic stem cell transplantation. However, graft-vs-host disease (GVHD) remains a major complication of this strategy. We have used escalating doses of DLI for many years, and wanted to assess the risk factors for GVHD and transplant-related mortality as well as disease outcomes according to the reason for DLI. We analyzed 65 patients who received a total of 111 DLI for different reasons and at different intervals after transplantation. Median number of DLI was 2 (range, 1-4), median interval between transplantation and DLI was 9 months (range, 1-41 months) and median number of infused CD3(+) cells/kg recipient body weight was 2.5 × 10(7) (range, 1 × 10(6)-11.8 × 10(7)). Reasons for DLI were relapse or progression in 37 patients (57%), residual disease in 15 patients (23%), and persistence of mixed chimerism in 13 patients (20%). Seven patients (11%) developed acute GVHD grade II to IV and 5 patients (8%) developed extensive chronic GVHD. In univariate analysis, we could identify a transplantation-DLI interval ≤6 months, the dose of DLI (≥1 × 10(7)), and DLI number as predictive factors of GVHD. In multivariate analysis, these results were confirmed only for the transplantation-DLI interval (hazard ratio = 19.48; 2.23-170.34; p = 0.007). Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD and transplant-related mortality, supporting further investigation as an upfront modality to enhance the graft-vs-tumor response in high-risk patients.
Experimental hematology 09/2012; · 3.11 Impact Factor
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Jean El-Cheikh,
Roberto Crocchiolo,
Jean-Marie Boher,
Sabine Furst,
Anne-Marie Stoppa,
Patrick Ladaique,
Catherine Faucher,
Boris Calmels,
Luca Castagna,
Claude Lemarie,
Jean-Marc Schiano De Colella,
Diane Coso, Reda Bouabdallah,
Christian Chabannon,
Didier Blaise
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to assess the results of allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from matched related donors (MRD) and unrelated donors (URD) in 40 patients with high-risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients (98%) received one or more autologous transplantation. The median follow-up was 22 months (1-49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs. (17%) for the MRD (P = 0.092). The cumulative incidence of chronic GVHD was no different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM probabilities were lower in the unrelated group 12% vs. 22% in the related group (P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation overall and progression-free survivals, 59% and 42%, respectively compared to patients with related donor transplantation, 66% and 44% (P = 0.241). In conclusion, these results suggest that URD in MM is feasible. The small number of patients with URD emphasizes the need to delineate indications and perform prospective protocols.
European Journal Of Haematology 03/2012; 88(6):497-503. · 2.61 Impact Factor
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Marie-Hélène Delfau-Larue,
Laurence de Leval,
Bertrand Joly,
Anne Plonquet,
Dominique Challine,
Marie Parrens,
Alain Delmer,
Gilles Salles,
Franck Morschhauser,
Richard Delarue,
Pauline Brice, Reda Bouabdallah,
Olivier Casasnovas,
Hervé Tilly,
Philippe Gaulard,
Corinne Haioun
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ABSTRACT: Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted.
Haematologica 02/2012; 97(10):1594-602. · 6.42 Impact Factor
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Jean El-Cheikh,
Roberto Crocchiolo,
Jean-Marie Boher,
Sabine Fürst,
Anne Marie Stoppa,
Catherine Faucher,
Luca Castagna,
Angela Granata,
Claire Oudin,
Jean-Marc Schiano De Colella,
Diane Coso, Reda Bouabdallah,
Mohamad Mohty,
Didier Blaise
Leukemia & lymphoma 02/2012; 53(8):1630-2. · 2.40 Impact Factor
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Nicolas Mounier,
Natacha Heutte,
Catherine Thieblemont,
Josette Briere,
Philippe Gaulard,
Pierre Feugier,
Hervé Ghesquieres,
Eric Van Den Neste,
Daniela Robu,
Herve Tilly, Reda Bouabdallah,
Violaine Safar,
Bertrand Coiffier
Clinical lymphoma, myeloma & leukemia 01/2012; 12(3):151-4.
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Raynier Devillier,
Diane Coso,
Luca Castagna,
Isabelle Brenot Rossi,
Antonella Anastasia,
Arturo Chiti,
Vadim Ivanov,
Jean Marc Schiano,
Armando Santoro,
Christian Chabannon,
Monica Balzarotti,
Didier Blaise, Reda Bouabdallah
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ABSTRACT: High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin's lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin's lymphoma.
We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin's lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation.
Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57-10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19-0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80-3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38-11.75]).
In patients with relapsed/refractory Hodgkin's lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation.
Haematologica 01/2012; 97(7):1073-9. · 6.42 Impact Factor
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Didier Blaise,
Laure Farnault,
Catherine Faucher,
Nicholas Marchetti,
Sabine Fürst,
Jean El Cheikh,
Patrick Ladaique,
Norbert Vey, Reda Bouabdallah,
Anne-Marie Stoppa,
Claude Lemarie,
Boris Calmels,
Thomas Prebet,
Luca Castagna,
Christian Chabannon,
Mohamad Mohty,
Benjamin Esterni
[show abstract]
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ABSTRACT: The development of reduced-intensity conditioning regimens rather than myeloablative regimens for allogeneic stem cell transplantation has led to decreased treatment-related mortality and increased use of this treatment modality, especially in older patients with hematological malignancies. No randomized controlled trials have been performed resulting in determining effectiveness on phase II studies, which rarely report on long-term survival.
In an attempt to address this limitation, we analyzed a single-center cohort of 100 consecutive patients with hematological malignancies undergoing allogeneic stem cell transplantation from a human leukocyte antigen-matched related donor with median follow-up of 60 months. The reduced-intensity conditioning regimen consisted of oral Busulfan, rabbit anti-thymocyte globulin, and Fludarabin.
Median age was 50 years (range, 18-64 years). The incidences of acute and chronic graft-vs.-host disease were 43% and 81%, respectively. The probability of nonrelapse mortality at 1 and 5 years was 15% and 25%, respectively. Nonrelapse mortality was adversely associated with acute graft-vs.-host disease (hazard ratio = 6; p = 0.0002). Of the 52 patients with measurable disease, 37 (71%) achieved a response. Relapse/progression occurred at a median of 11 months (range 1-52 months) in 21 patients, for a cumulative incidence of 22%. The probability of overall survival and progression-free survival at 5 years were 60% and 54%, respectively. Overall survival and progression-free survival were favorably influenced by having had previous autologous stem cell transplantation and a low CD34(+) cell dose. Overall survival, progression-free survival, and nonrelapse mortality improved over time in this cohort of patients.
These results are encouraging for populations different in term of age, diagnosis, and disease status.
Experimental hematology 12/2010; 38(12):1241-50. · 3.11 Impact Factor
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Vadim Ivanov,
Emeline Tabouret,
Guillaume Chuto,
Bruno Chetaille,
Hacène Fezoui,
Diane Coso,
Jerome Rey,
Therese Aurran-Schleinitz,
Jean Marc Schiano,
Anne Marie Stoppa,
Didier Blaise, Reda Bouabdallah
Leukemia & lymphoma 09/2010; 51(9):1758-60. · 2.40 Impact Factor
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Delphine Rolland,
Vincent Ribrag,
Corinne Haioun,
Herve Ghesquieres,
Fabrice Jardin, Reda Bouabdallah,
Patricia Franchi,
Josette Briere,
Eric De Kerviler,
Catherine Chassagne-Clement,
Mitch Raponi,
Remi Houlgatte,
Jean-Philippe Jais,
Catherine Thieblemont
[show abstract]
[hide abstract]
ABSTRACT: Farnesyltransferase (Ftase) was identified by gene-expression profiling and by preclinical evaluation in in vitro and in vivo mantle cell lymphoma (MCL) models as a rational therapeutic target in MCL, one of the most refractory B-cell lymphomas. We conducted a multicenter phase II study of a potent Ftase inhibitor, tipifarnib, in patients with relapsed or refractory MCL.
Tipifarnib was administered at 300 mg orally twice daily for the first 21 days of each 28-day cycle for 4 cycles, and in case of response for 6 cycles. Study endpoints were objective response at 4 and 6 cycles, progression free survival (PFS), overall survival, and toxicity. Prediction of response was retrospectively evaluated in the initial tumor biopsy by the RASGRP1/APTX gene expression ratio, and the AKAP13 expression level.
Eleven patients (median age, 71 years) were enrolled. Patients received a median number of three prior therapies (range 1-11). Nine patients completed at least 3 cycles of tipifarnib. No grade III-IV hematological toxicities were recorded. One patient presented a complete response (CR) after 4 and a persistent CR at 6 cycles (ORR = 9%). Median PFS was 3 months (range 0.7-14.2). The RASGRP1/APTX gene expression ratio was higher in the responder (n = 1) while the AKAP13 expression was higher in the non-responders (n = 2). This corresponds to the expected result for predicting response to tipifarnib.
Treatment with tipifarnib relapsed or refractory MCL is associated with low response rates. Limited gene expression studies suggest that response may be associated with molecular targets.
Cancer Chemotherapy and Pharmacology 12/2009; 65(4):781-90. · 2.83 Impact Factor
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Bruno Chetaille,
François Bertucci,
Pascal Finetti,
Benjamin Esterni,
Aspasia Stamatoullas,
Jean Michel Picquenot,
Marie Christine Copin,
Frank Morschhauser,
Olivier Casasnovas,
Tony Petrella,
Thierry Molina,
Anne Vekhoff,
Pierre Feugier, Reda Bouabdallah,
Daniel Birnbaum,
Daniel Olive,
Luc Xerri
[show abstract]
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ABSTRACT: The outcome of classical Hodgkin lymphoma (cHL) patients may be related to the tumor microenvironment, which in turn may be influenced by Epstein-Barr virus (EBV) infection. To characterize the cHL microenvironment, a set of 63 cHL tissue samples was profiled using DNA microarrays. Their gene expression profile differed from that of histiocyte T cell-rich B-cell lymphoma (H/TCRBCL) samples that were used as controls, mainly due to high expression of PDCD1/PD-1 in H/TCRBCL. EBV(+) cHL tissues could be distinguished from EBV(-) samples by a gene signature characteristic of Th1 and antiviral responses. Samples from cHL patients with favorable outcome overexpressed genes specific for B cells and genes involved in apoptotic pathways. An independent set of 146 cHL samples was analyzed using immunohistochemistry. It showed a significant adverse value in case of high percentage of either TIA-1(+)-reactive cells or topoisomerase-2(+) tumor cells, whereas high numbers of BCL11A(+), FOXP3(+), or CD20(+) reactive cells had a favorable influence. Our results suggest an antitumoral role for B cells in the cHL microenvironment and a stronger stromal influence of the PD1 pathway in H/TCRBCL than cHL. The observation of Th1/ antiviral response in EBV(+) cHL tissues provides a basis for novel treatment strategies.
Blood 01/2009; 113(12):2765-3775. · 9.90 Impact Factor
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Franck Morschhauser,
Pauline Brice,
Christophe Fermé,
Marine Diviné,
Gilles Salles, Reda Bouabdallah,
Catherine Sebban,
Laurent Voillat,
Olivier Casasnovas,
Aspasia Stamatoullas,
Krimo Bouabdallah,
Marc André,
Jean-Philippe Jais,
Dominique Cazals-Hatem,
Christian Gisselbrecht
[show abstract]
[hide abstract]
ABSTRACT: A prospective multicenter trial evaluated a risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation (ASCT) for 245 Hodgkin's lymphoma (HL) patients who experience treatment failure with first-line therapy.
Poor-risk patients (150 with primary refractory disease or > or = two of the following risk factors at first relapse: time to relapse < 12 months, stage III or IV at relapse, and relapse within previously irradiated sites) or intermediate-risk patients (95 with one risk factor at relapse) were eligible for tandem or single ASCT, respectively.
Among poor-risk patients, 105 (70%), including 30 of 55 with cytoreductive chemotherapy-resistant disease, received tandem ASCT, whereas 92 intermediate-risk patients (97%) received single ASCT. According to intent-to-treat analysis, the 5-year freedom from second failure and overall survival (OS) estimates were 73% and 85%, respectively, for the intermediate-risk group and 46% and 57%, respectively, for the poor-risk group. Outcomes were similar for primary refractory and poor-risk/relapsed HL. For patients with chemotherapy-resistant disease, the 46% 5-year OS rate achieved with tandem ASCT compares favorably with the previously reported 30%. Outcomes for partial and complete responders to cytoreduction receiving tandem ASCT did not differ significantly and were better than those previously reported for partial responders receiving single ASCT, but not superior to those reported for complete responders receiving single ASCT. Six poor-risk patients (4%) died from toxicity.
Single ASCT is appropriate for intermediate-risk patients. For poor-risk patients, our results suggest a benefit of tandem ASCT for half of the patients with chemotherapy-resistant disease and partial responders, but not for complete responders to cytoreductive chemotherapy.
Journal of Clinical Oncology 11/2008; 26(36):5980-7. · 18.37 Impact Factor
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Gilles Salles,
Nicolas Mounier,
Sophie de Guibert,
Franck Morschhauser,
Chantal Doyen,
Jean-François Rossi,
Corinne Haioun,
Pauline Brice,
Béatrice Mahé, Reda Bouabdallah,
Bruno Audhuy,
Christophe Ferme,
Caroline Dartigeas,
Pierre Feugier,
Catherine Sebban,
Luc Xerri,
Charles Foussard
[show abstract]
[hide abstract]
ABSTRACT: The FL2000 study was undertaken to evaluate the combination of the anti-CD20 monoclonal antibody rituximab with chemotherapy plus interferon in the first-line treatment of follicular lymphoma patients with a high tumor burden. Patients were randomly assigned to receive either 12 courses of the chemotherapy regimen CHVP (cyclophosphamide, adriamycin, etoposide, and prednisolone) plus interferon-alpha2a (CHVP+I arm) over 18 months or 6 courses of the same chemotherapy regimen combined with 6 infusions of 375 mg/m(2) rituximab and interferon for the same time period (R-CHVP+I arm). After a median follow-up of 5 years, event-free survival estimates were, respectively, 37% (95% confidence interval [CI], 29%-44%) and 53% (95% CI, 45%-60%) in the CHVP+I and R-CHVP+I arm (P = .001). Five-year overall survival estimates were not statistically different in the CHVP+I (79%; 95% CI, 72%-84%) and R-CHVP+I (84%; 95% CI, 78%-84%) arms. In a multivariate regression analysis, event-free survival was significantly influenced by both the Follicular Lymphoma International Prognostic Index score (hazard ratio = 2.08; 95% CI, 1.6%-2.8%) and the treatment arm (hazard ratio = 0.59; 95% CI, 0.44%-0.78%). With a 5-year follow-up, the combination of rituximab with CHVP+I provides superior disease control in follicular lymphoma patients despite a shorter duration of chemotherapy. This study's clinical trial was registered at the National Institutes of Health website as no. NCT00136552.
Blood 10/2008; 112(13):4824-31. · 9.90 Impact Factor
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Hugues de Lavallade,
Philippe A Cassier, Reda Bouabdallah,
Jean El-Cheikh,
Catherine Faucher,
Sabine Fürst,
Diane Coso,
Danielle Sainty,
Christine Arnoulet,
Jean-Albert Gastaut,
Bruno Chetaille,
Luc Xerri,
Didier Blaise,
Mohamad Mohty
British Journal of Haematology 09/2008; 142(5):848-50. · 4.94 Impact Factor
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Jehan Dupuis,
Jean-François Emile,
Nicolas Mounier,
Christian Gisselbrecht,
Nadine Martin-Garcia,
Tony Petrella, Reda Bouabdallah,
Françoise Berger,
Alain Delmer,
Bertrand Coiffier,
Félix Reyes,
Philippe Gaulard
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ABSTRACT: Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been detected in around 40% of cases, but its prognostic significance is not fully established. Lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male sex (80% versus 60%, respectively, P = .02). Only 50% of patients achieved complete remission with a 5-year event-free survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a 5-year probability of 11% for positive patients. In univariate analysis, factors affecting OS were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse OS in the elderly population. Time-dependent analysis showed that the negative impact of EBV was essentially seen in the first 2 years following diagnosis. These results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients.
Blood 01/2007; 108(13):4163-9. · 9.90 Impact Factor
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Hugues de Lavallade,
Mohamad Mohty,
Jean El-Cheikh,
Philippe A Cassier,
Catherine Faucher,
Sabine Fürst,
Norbert Vey,
Anne-Marie Stoppa,
Daniele Sainty,
Christine Arnoulet,
Luc Xerri,
Jean-Albert Gastaut,
Didier Blaise, Reda Bouabdallah
British Journal of Haematology 12/2006; 135(3):408-10. · 4.94 Impact Factor
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ABSTRACT: This study investigated the role of inflammatory cytokines in acute graft-versus-host disease (aGVHD) incidence and severity in 113 patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Among all tested cytokines in the first 3 months after allo-SCT, only interleukin-12 p70 (IL-12p70) levels in the first month were significantly associated with grades II to IV aGVHD development (P < .001). IL-12p70 levels were directly correlated with aGVHD severity grade (P < .001). Before aGVHD onset, blood monocytes, the main precursor pool of IL12p70-secreting dendritic cells, recovered more rapidly in patients with grades II to IV aGVHD (P = .005). Similarly, at the effector level, there was a more robust reconstitution of naive CD3+CD4+CD45RA+CD27+ T cells in patients developing grades II to IV aGVHD (P = .006). In multivariate analysis, IL-12p70 level measured in the first month was the strongest predictive factor for aGVHD development (P < .001). These findings, reconstituting a T(H)1 loop, support a model in which aGVHD reflects a type 1 alloreaction after RIC allo-SCT.
Blood 01/2006; 106(13):4407-11. · 9.90 Impact Factor
