Treatment of mantle-cell lymphomas with the VAD +/− chiorambucil regimen with or without subsequent high-dose therapy and peripheral blood stem-cell transplantation

Gressin, Rémy; Legouffe, Eric; Leroux, Dominique; Jacob, Marie‐Christine; Świercz, P; Péoc’h, Michel; Capdevilla, V.; Rossi, Jean François; Thyss, A.; Jj, Sotto

doi:10.1093/annonc/8.suppl_1.s103

Cited by 12 publications

(7 citation statements)

References 18 publications

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“…[17][18][19] Only one out of seven patients entered CR after chlorambucil-VAD which is substantially fewer in our experience than patients with classic forms of MCL. 20 The response to single agent or CVP was very poor with only one response out of seven patients. However, the overall duration of response after first-line therapy was very short, estimated at 11 months and 10 of the 12 complete responders relapsed.…”

Section: Figurementioning

confidence: 97%

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype

Bernard¹,

et al. 2001

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The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P Ͻ0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI у2 had 8 months median OS as compared to 36 months median OS for patients with IPI Ͻ2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5 + NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients. Leukemia (2001) 15, 1785-1791.

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Section: Figurementioning

confidence: 97%

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype

Bernard¹,

et al. 2001

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“…23 However, response criteria in all these studies did not include bone marrow and gastrointestinal examination. Taken together, these studies suggest that for a large proportion of patients with MCL, CHOP or CHOP-like regimens failed to obtain a minimal tumor burden before stem cell collection and intensive therapy plus APBSCT.…”

Section: 21mentioning

confidence: 99%

“…We have chosen DHAP because high-dose Arac is an effective therapy in obtaining complete response in patients in relapse of aggressive NHL. [23][24][25] Furthermore, this drug allows intensification with APBSCT and may induce cure of aggressive relapsing NHL. In our series this regimen produced a high rate of CR (84%) and good PR (8%) after failure of CHOP without life-threatening toxicity.…”

Section: Figurementioning

confidence: 99%

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study

et al. 2002

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Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twentyfive patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabinemelphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.

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“…The goal of LM 1996 was to evaluate the efficacy and tolerance of the VAD+C regimen. 18 This trial was opened for patients aged between 18 and 75 years old. The primary objective of LM2001 was to evaluate the association of rituximab to the VAD+C, in terms of efficacy and toxicity in patients under 65 years of age.…”

Section: Methodsmentioning

confidence: 99%

“…17 Here we report the long-term follow-up results of two French GOELAMS studies which evaluated the tolerance and efficacy of the VAD+C regimen with or without rituximab in a total of 113 newly diagnosed MCL patients. 18 The prognostic value of the recently-devised MIPI score 19 and Ki67 expression status were also evaluated.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group

et al. 2010

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The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3-4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3-4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively. Conclusions The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: NCT00285389).

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Treatment of mantle-cell lymphomas with the VAD +/− chiorambucil regimen with or without subsequent high-dose therapy and peripheral blood stem-cell transplantation

Cited by 12 publications

References 18 publications

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study

Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group

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