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Olivier Hermine - One of the best experts on this subject based on the ideXlab platform.
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validation of the mcl35 gene expression proliferation assay in randomized trials of the european Mantle Cell Lymphoma network
British Journal of Haematology, 2019Co-Authors: Hilka Rauertwunderlich, Wolfram Klapper, Olivier Hermine, Hanneke C Kluinnelemans, Sylvia Hartmann, Anja Mottok, David W Scott, Lisa M Rimsza, Michael Unterhalt, Christoph ThornsAbstract:Mantle Cell Lymphoma (MCL) is still considered incurable and the course of the disease is highly variable. Established risk factors include the Mantle Cell Lymphoma International Prognostic Index (MIPI) and the quantification of the proliferation rate of the tumour Cells, e.g. by Ki-67 immunohistochemistry. In this study, we aimed to validate the prognostic value of the gene expression-based MCL35 proliferation assay in patient cohorts from randomized trials of the European Mantle Cell Lymphoma Network. Using this assay, we analysed the gene expression proliferation signature in routine diagnostic lymph node specimens from MCL Younger and MCL Elderly trial patients, and the calculated MCL35 score was used to assign MCL patients to low (61%), standard (27%) or high (12%) risk groups with significantly different outcomes. We confirm here in our prospective clinical trial cohort of MCL patients, that the MCL35 assay is strongly prognostic, providing additional information to the Ki-67 index and the MIPI. Thus, this robust assay may assist in making treatment decisions or in devising risk-adapted prospective clinical trials in the future.
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addition of high dose cytarabine to immunochemotherapy before autologous stem Cell transplantation in patients aged 65 years or younger with Mantle Cell Lymphoma mcl younger a randomised open label phase 3 trial of the european Mantle Cell Lymphoma n
The Lancet, 2016Co-Authors: Michal Szymczyk, Andre Bosly, Reda Bouabdallah, Eva Hoster, Stephan Stilgenbauer, Olivier Hermine, Catherine Thieblemont, Jan Walewski, Michael KnebaAbstract:Summary Background Mantle Cell Lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-Cell transplantation (ASCT) improves outcome. Methods This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II–IV Mantle Cell Lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II–IV Mantle Cell Lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Findings Of 497 patients (median age 55 years [IQR 49–60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6·1 years (95% CI 5·4–6·4), time to treatment failure was significantly longer in the cytarabine group (median 9·1 years [95% CI 6·3–not reached], 5 year rate 65% [95% CI 57–71]) than in the control group (3·9 years [3·2–4·4], 40% [33–46]; hazard ratio 0·56; p=0·038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241m vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of ASCT-related deaths was similar (eight [3·4%]) in both groups. Interpretation Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with Mantle Cell Lymphoma. Funding European Commission, Lymphoma Research Foundation, and Roche.
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confirmation of the Mantle Cell Lymphoma international prognostic index in randomized trials of the european Mantle Cell Lymphoma network
Journal of Clinical Oncology, 2014Co-Authors: Eva Hoster, Christian H Geisler, Marek Trneny, Achiel Van Hoof, Wolfram Klapper, Olivier Hermine, Hanneke C Kluinnelemans, Jan Walewski, Francesco Di RaimondoAbstract:Purpose Mantle-Cell Lymphoma (MCL) is a distinct B-Cell Lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned to be performed on the cohort of the two recently completed randomized trials of the European MCL Network. Patients and Methods Data of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI with respect to overall survival (OS) and time to treatment failure (TTF). Results Five-year OS rates in MIPI low, intermediate, and high-risk groups were 83%, 63%, and 34%, respectively. The hazard ratios for OS of intermediate versus low and high versus intermediate risk patients were 2.1 (95% CI, 1.5 to 2.9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline character...
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treatment of older patients with Mantle Cell Lymphoma
The New England Journal of Medicine, 2012Co-Authors: Hanneke C Kluinnelemans, Christian H Geisler, Marek Trneny, Eva Hoster, Stephan Stilgenbauer, Olivier Hermine, Catherine Thieblemont, Jan Walewski, Ursula Vehlingkaiser, J K DoorduijnAbstract:We randomly assigned patients 60 years of age or older with Mantle-Cell Lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of ritux imab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to main tenance therapy with rituximab or interferon alfa, each given until progression. RESULTS Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P = 0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P = 0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects oc curred more frequently in the R-FC group than in the R-CHOP group, but the fre quency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% con fidence interval, 0.36 to 0.87; P = 0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall sur vival (4-year survival rate, 87%, vs. 63% with interferon alfa; P = 0.005). CONCLUSIONS R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with Mantle-Cell Lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.)
Eva Hoster - One of the best experts on this subject based on the ideXlab platform.
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prognostic value of ki 67 index cytology and growth pattern in Mantle Cell Lymphoma results from randomized trials of the european Mantle Cell Lymphoma network
Journal of Clinical Oncology, 2016Co-Authors: Eva Hoster, Andreas Rosenwald, Francoise Berger, Heinzwolfram Bernd, Sylvia Hartmann, Christoph Loddenkemper, Thomas F E Barth, Nicole Brousse, Stefano Pileri, Grzegorz RymkiewiczAbstract:PurposeMantle-Cell Lymphoma (MCL) is a rather aggressive B-Cell malignancy whose considerable variability of individual outcome is associated with clinical characteristics (Mantle Cell Lymphoma International Prognostic Index [MIPI]). The Ki-67 index is a strong independent prognostic factor; however, the biologic MIPI (MIPI-b) distinguishes only two groups, which does not appropriately depict the clinical heterogeneity. By using the cohort from the European MCL Younger and MCL Elderly trials, we aimed to evaluate the additional prognostic impact of cytology and growth pattern and to improve risk stratification with the Ki-67 index and MIPI.Patients and MethodsDiagnostic tumor biopsies were reviewed by the European Mantle Cell Lymphoma Pathology Panel to determine Ki-67 index by using published guidelines, cytology, and growth pattern. We evaluated prognostic effects for overall survival (OS) by Cox regression. For the cohort used for MIPI-b development (German Low-Grade Lymphoma Study Group [GLSG] 1996 an...
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addition of high dose cytarabine to immunochemotherapy before autologous stem Cell transplantation in patients aged 65 years or younger with Mantle Cell Lymphoma mcl younger a randomised open label phase 3 trial of the european Mantle Cell Lymphoma n
The Lancet, 2016Co-Authors: Michal Szymczyk, Andre Bosly, Reda Bouabdallah, Eva Hoster, Stephan Stilgenbauer, Olivier Hermine, Catherine Thieblemont, Jan Walewski, Michael KnebaAbstract:Summary Background Mantle Cell Lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-Cell transplantation (ASCT) improves outcome. Methods This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II–IV Mantle Cell Lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II–IV Mantle Cell Lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Findings Of 497 patients (median age 55 years [IQR 49–60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6·1 years (95% CI 5·4–6·4), time to treatment failure was significantly longer in the cytarabine group (median 9·1 years [95% CI 6·3–not reached], 5 year rate 65% [95% CI 57–71]) than in the control group (3·9 years [3·2–4·4], 40% [33–46]; hazard ratio 0·56; p=0·038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241m vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of ASCT-related deaths was similar (eight [3·4%]) in both groups. Interpretation Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with Mantle Cell Lymphoma. Funding European Commission, Lymphoma Research Foundation, and Roche.
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confirmation of the Mantle Cell Lymphoma international prognostic index in randomized trials of the european Mantle Cell Lymphoma network
Journal of Clinical Oncology, 2014Co-Authors: Eva Hoster, Christian H Geisler, Marek Trneny, Achiel Van Hoof, Wolfram Klapper, Olivier Hermine, Hanneke C Kluinnelemans, Jan Walewski, Francesco Di RaimondoAbstract:Purpose Mantle-Cell Lymphoma (MCL) is a distinct B-Cell Lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned to be performed on the cohort of the two recently completed randomized trials of the European MCL Network. Patients and Methods Data of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI with respect to overall survival (OS) and time to treatment failure (TTF). Results Five-year OS rates in MIPI low, intermediate, and high-risk groups were 83%, 63%, and 34%, respectively. The hazard ratios for OS of intermediate versus low and high versus intermediate risk patients were 2.1 (95% CI, 1.5 to 2.9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline character...
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treatment of older patients with Mantle Cell Lymphoma
The New England Journal of Medicine, 2012Co-Authors: Hanneke C Kluinnelemans, Christian H Geisler, Marek Trneny, Eva Hoster, Stephan Stilgenbauer, Olivier Hermine, Catherine Thieblemont, Jan Walewski, Ursula Vehlingkaiser, J K DoorduijnAbstract:We randomly assigned patients 60 years of age or older with Mantle-Cell Lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of ritux imab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to main tenance therapy with rituximab or interferon alfa, each given until progression. RESULTS Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P = 0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P = 0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects oc curred more frequently in the R-FC group than in the R-CHOP group, but the fre quency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% con fidence interval, 0.36 to 0.87; P = 0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall sur vival (4-year survival rate, 87%, vs. 63% with interferon alfa; P = 0.005). CONCLUSIONS R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with Mantle-Cell Lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.)
Evgenii Osmanov - One of the best experts on this subject based on the ideXlab platform.
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bortezomib based therapy for newly diagnosed Mantle Cell Lymphoma
The New England Journal of Medicine, 2015Co-Authors: Tadeusz Robak, Olga Samoilova, Halyna Pylypenko, Noppadol Siritanaratkul, Huiqiang Huang, Gregor Verhoef, Jie Jin, Ting Liu, Jun Zhu, Evgenii OsmanovAbstract:BackgroundThe proteasome inhibitor bortezomib was initially approved for the treatment of relapsed Mantle-Cell Lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed Mantle-Cell Lymphoma. MethodsIn this phase 3 trial, we randomly assigned 487 adults with newly diagnosed Mantle-Cell Lymphoma who were ineligible or not considered for stem-Cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. ResultsAfter a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-C...
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Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma
New England Journal of Medicine, 2015Co-Authors: Tadeusz Robak, Olga Samoilova, Halyna Pylypenko, Noppadol Siritanaratkul, Huiqiang Huang, Gregor Verhoef, Jie Jin, Ting Liu, Jun Zhu, Evgenii OsmanovAbstract:BACKGROUND: The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed Mantle-Cell Lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed Mantle-Cell Lymphoma. METHODS: In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed Mantle-Cell Lymphoma who were ineligible or not considered for stem-Cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. RESULTS: After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P
Chan Yoon Cheah - One of the best experts on this subject based on the ideXlab platform.
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Mantle Cell Lymphoma
Journal of Clinical Oncology, 2016Co-Authors: Chan Yoon Cheah, John F Seymour, Michael WangAbstract:Mantle Cell Lymphoma (MCL) is an uncommon subtype of non-Hodgkin Lymphoma previously considered to have a poor prognosis. Large gains were made in the first decade of the new century when clinical trials established the importance of high-dose therapy and autologous stem-Cell rescue and high-dose cytarabine in younger patients and the benefits of maintenance rituximab and bendamustine in older patients. In particular, greater depth of understanding of the molecular pathophysiology of MCL has resulted in an explosion of specifically targeted new efficacious agents. In particular, agents recently approved by the Food and Drug Administration include the proteasome inhibitor bortezomib, immunomodulator lenalidomide, and Bruton’s tyrosine kinase inhibitor ibrutinib. We review recent advances in the understanding of MCL biology and outline our recommended approach to therapy, including choice of chemoimmunotherapy, the role of stem-Cell transplantation, and mechanism-based targeted therapies, on the basis of a ...
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Mantle Cell Lymphoma
Journal of Clinical Oncology, 2016Co-Authors: Chan Yoon Cheah, John F Seymour, Michael L. WangAbstract:Mantle Cell Lymphoma (MCL) is an uncommon subtype of non-Hodgkin Lymphoma previously considered to have a poor prognosis. Large gains were made in the first decade of the new century when clinical trials established the importance of high-dose therapy and autologous stem-Cell rescue and high-dose cytarabine in younger patients and the benefits of maintenance rituximab and bendamustine in older patients. In particular, greater depth of understanding of the molecular pathophysiology of MCL has resulted in an explosion of specifically targeted new efficacious agents. In particular, agents recently approved by the Food and Drug Administration include the proteasome inhibitor bortezomib, immunomodulator lenalidomide, and Bruton's tyrosine kinase inhibitor ibrutinib. We review recent advances in the understanding of MCL biology and outline our recommended approach to therapy, including choice of chemoimmunotherapy, the role of stem-Cell transplantation, and mechanism-based targeted therapies, on the basis of a synthesis of the data from published clinical trials.
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central nervous system involvement in Mantle Cell Lymphoma clinical features prognostic factors and outcomes from the european Mantle Cell Lymphoma network
Annals of Oncology, 2013Co-Authors: Hanneke C Kluinnelemans, Wojciech Jurczak, Chan Yoon Cheah, Anupkumar George, Eva Gine, Annalisa Chiappella, Katarzyna Krawczyk, Heidi Mocikova, Pavel KlenerAbstract:Central nervous system (CNS) involvement in Mantle Cell Lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status >= 2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of >= 1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood Cell count at diagnosis <10.9 x 10(9)/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem Cell transplant and achievement of complete response were all associated with improved survival. In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.
Hanneke C Kluinnelemans - One of the best experts on this subject based on the ideXlab platform.
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validation of the mcl35 gene expression proliferation assay in randomized trials of the european Mantle Cell Lymphoma network
British Journal of Haematology, 2019Co-Authors: Hilka Rauertwunderlich, Wolfram Klapper, Olivier Hermine, Hanneke C Kluinnelemans, Sylvia Hartmann, Anja Mottok, David W Scott, Lisa M Rimsza, Michael Unterhalt, Christoph ThornsAbstract:Mantle Cell Lymphoma (MCL) is still considered incurable and the course of the disease is highly variable. Established risk factors include the Mantle Cell Lymphoma International Prognostic Index (MIPI) and the quantification of the proliferation rate of the tumour Cells, e.g. by Ki-67 immunohistochemistry. In this study, we aimed to validate the prognostic value of the gene expression-based MCL35 proliferation assay in patient cohorts from randomized trials of the European Mantle Cell Lymphoma Network. Using this assay, we analysed the gene expression proliferation signature in routine diagnostic lymph node specimens from MCL Younger and MCL Elderly trial patients, and the calculated MCL35 score was used to assign MCL patients to low (61%), standard (27%) or high (12%) risk groups with significantly different outcomes. We confirm here in our prospective clinical trial cohort of MCL patients, that the MCL35 assay is strongly prognostic, providing additional information to the Ki-67 index and the MIPI. Thus, this robust assay may assist in making treatment decisions or in devising risk-adapted prospective clinical trials in the future.
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confirmation of the Mantle Cell Lymphoma international prognostic index in randomized trials of the european Mantle Cell Lymphoma network
Journal of Clinical Oncology, 2014Co-Authors: Eva Hoster, Christian H Geisler, Marek Trneny, Achiel Van Hoof, Wolfram Klapper, Olivier Hermine, Hanneke C Kluinnelemans, Jan Walewski, Francesco Di RaimondoAbstract:Purpose Mantle-Cell Lymphoma (MCL) is a distinct B-Cell Lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned to be performed on the cohort of the two recently completed randomized trials of the European MCL Network. Patients and Methods Data of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI with respect to overall survival (OS) and time to treatment failure (TTF). Results Five-year OS rates in MIPI low, intermediate, and high-risk groups were 83%, 63%, and 34%, respectively. The hazard ratios for OS of intermediate versus low and high versus intermediate risk patients were 2.1 (95% CI, 1.5 to 2.9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline character...
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central nervous system involvement in Mantle Cell Lymphoma clinical features prognostic factors and outcomes from the european Mantle Cell Lymphoma network
Annals of Oncology, 2013Co-Authors: Hanneke C Kluinnelemans, Wojciech Jurczak, Chan Yoon Cheah, Anupkumar George, Eva Gine, Annalisa Chiappella, Katarzyna Krawczyk, Heidi Mocikova, Pavel KlenerAbstract:Central nervous system (CNS) involvement in Mantle Cell Lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status >= 2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of >= 1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood Cell count at diagnosis <10.9 x 10(9)/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem Cell transplant and achievement of complete response were all associated with improved survival. In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.
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treatment of older patients with Mantle Cell Lymphoma
The New England Journal of Medicine, 2012Co-Authors: Hanneke C Kluinnelemans, Christian H Geisler, Marek Trneny, Eva Hoster, Stephan Stilgenbauer, Olivier Hermine, Catherine Thieblemont, Jan Walewski, Ursula Vehlingkaiser, J K DoorduijnAbstract:We randomly assigned patients 60 years of age or older with Mantle-Cell Lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of ritux imab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to main tenance therapy with rituximab or interferon alfa, each given until progression. RESULTS Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P = 0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P = 0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects oc curred more frequently in the R-FC group than in the R-CHOP group, but the fre quency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% con fidence interval, 0.36 to 0.87; P = 0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall sur vival (4-year survival rate, 87%, vs. 63% with interferon alfa; P = 0.005). CONCLUSIONS R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with Mantle-Cell Lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.)