Autologous Stem Cell Transplantation and Rituximab for Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2092-2092
Author(s):  
Francisco Javier Capote ◽  
E. González-Barca ◽  
J.M. Bergua ◽  
M.J. Pascual ◽  
R. García-Boyero ◽  
...  

Abstract Introduction: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma comprising up 5% of non-Hodgkins lymphomas. Although the prognosis for MCL patients has improved in recent years, the outlook for those with advanced or recurrent disease remains poor and the role of hematopoietic stem cell transplantation is unclear. The HyperCVAD-M/A regimen (fractionated high-dose cyclophosphamide, vincristine, doxorubicin and prednisolone alternated with methotraxate and cytarabine) has yielded encouraging results when combined with autologous stem cell transplantation (ASCT). In an effort to improve these results further, we have combined rituximab in vivo purging and post-transplant consolidation with HyperCVAD-M/A plus ASCT. Methods: Patients aged <65 years with previously untreated or relapsed MCL were treated with four courses of HyperCVAD-M/A followed by four once-weekly doses of rituximab 375mg/m2 as purging prior to stem cell mobilization and harvesting, high-dose chemotherapy (ICT-CY or BEAM), stem cell reinfusion and four further doses of rituximab immunotherapy post-transplant. Results: Of the 40 patients enrolled so far, 20 (15 male, 5 female; 18 previously untreated) have been transplanted. The median age was 50 years (range 38–63 years). After the final post-ASCT immunotherapy all 20 patients were in clinical complete remission. With a median follow-up of 36 months from diagnosis (range 7–64 months), 18 patients remain alive with 13 in complete remission. One patient died 15 months post-ASCT without evidence of disease recurrence. Kaplan-Meier estimates of 5-year overall and event-free survival are 90% and 65% respectively. Conclusions: This approach seems safe and feasible and produces durable remissions; longer follow-up of a more patients will be required to assess the effect of the procedure on survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1390-1390
Author(s):  
Francisco J. Capote ◽  
M. J. Pascual ◽  
E. Gonzalez-Barca ◽  
J. M. Bergua ◽  
A. Jimenez ◽  
...  

Abstract Introduction: Mantle cell lymphoma (MCL) is a CD20+ malignancy comprising up 5% of non-Hodgkin’s lymphomas, and has a poor prognosis under standard chemotherapy. The HyperCVAD-M/A regimen (fractionated high-dose cyclophosphamide, vincristine, doxorubicin and prednisolone alternated with methotraxate and cytarabine) has yielded encouraging results when combined with autologous stem cell transplantation (ASCT) in MCL, with 5-year failure-free survival of 54% and overall survival 72%. In an effort to improve these results further, we have combined rituximab in vivo purging and post-transplant consolidation with HyperCVAD-M/A plus ASCT. Methods: Patients aged <65 years with previously untreated or relapsed MCL were treated with four courses of HyperCVAD-M/A followed by four once-weekly doses of rituximab 375mg/m2 as purging prior to stem cell mobilization and harvesting, high-dose chemotherapy (ICT-CY or BEAM), stem cell reinfusion and four further doses of rituximab immunotherapy post-transplant. Results: Of the 34 patients enrolled so far, 15 (12 male, 3 female; 12 previously untreated) have been transplanted. The median age was 52 years (range 47–63 years). After the final post-ASCT immunotherapy all 15 patients were in clinical complete remission. With a median follow-up of 30 months from diagnosis (range 7–52 months), 14 patients remain alive with 13 in first complete remission. One patient died 15 months post-ASCT without evidence of disease recurrence. Kaplan-Meier estimates of 4-year overall and event-free survival are 93.3% and 86.6% respectively. Conclusions: This approach seems safe and feasible and produces durable remissions; longer follow-up of a more patients will be required to assess the effect of the procedure on survival.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 581-581 ◽  
Author(s):  
Richard Delarue ◽  
Corinne Haioun ◽  
Vincent Ribrag ◽  
Pauline Brice ◽  
Alain Delmer ◽  
...  

Abstract Introduction: Treatment of mantle cell lymphoma (MCL) in younger patients (pts) is still a challenge, with questions about best induction regimen before autologous stem cell transplantation (ASCT) and impact of Rituximab. We report here the final results with extended follow-up of a prospective phase II trial. Methods: Patients under 66 years with histologically proven, stage III-IV, MCL were included. Treatment consisted of three courses of CHOP with Rituximab at the third one and three courses of RDHAP. Peripheral blood stem cells harvest was performed and responding pts were eligible for an ASCT after high dose radio-chemotherapy with TAM6 (TBI 10 Gy, Aracytine 6 g/m², Melphalan 140 mg/m²) or BEAM if TBI could not be performed. Results: From May 2000 to September 2003, 60 pts were included. Median age was 57 years. Characteristics of patients were as follow : bone marrow involvement 85%, leukemic disease 48%, gastrointestinal involvment 52%, PS&gt;1 6%, LDH &gt; 1N 38%. Overall response rate was high with 93% after (R)CHOP and 95% after RDHAP. Interestingly, CR was uncommon after (R)CHOP (12%), whereas high proportion of patients (61%) were in CR after RDHAP, suggesting higher efficacy of high dose AraC. Forty-nine pts were autografted (41 with TAM6) : all patients but two (96%) were in CR. With a median follow-up of 67 months, median EFS was 83 months and median OS was not reached. Five years OS was 75%. Neither toxic death nor unexpected toxicities were observed. The comparison with our previous French oligocentric study using the same regimen but without Rituximab (Lefrere, Hematologica 2007) suggests a better outcome when Rituximab is added (median EFS : 51 months). Conclusion: This study confirms that regimens containing Aracytine and Rituximab are safe and prolong survival and may even induce cure in MCL patients. Thus, they should be used in induction treatment before ASCT. This regimen is currently compared with the classical RCHOP induction in a multicentric European protocol within the EMCL network.


Cancer ◽  
2005 ◽  
Vol 104 (7) ◽  
pp. 1434-1441 ◽  
Author(s):  
Catherine Thieblemont ◽  
Daciana Antal ◽  
Laurence Lacotte-Thierry ◽  
Vincent Delwail ◽  
Daniel Espinouse ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2734-2734 ◽  
Author(s):  
Mars B. Van’t Veer ◽  
Annelise Notenboom ◽  
Marius McKenzie ◽  
Hanneke Kluin-Nelemans ◽  
Rien van Oers ◽  
...  

Abstract The Dutch Hemato-Oncology Study Group (HOVON) evaluated in a phase II trial the efficacy of the addition of rituximab, high dose Ara-C and autologous stem cell transplantation after BEAM conditioning to conventional CHOP in 88 previously untreated patients with mantle cell lymphoma, with respect to remission rate, failure free survival (FFS) and overall survival (OS). From 2002 to 2005, 86 eligible patients were included and evaluated. The male : female ratio was: 4 and the median age 55 years (32–66). Median follow-up of all patients still alive was 25.5 months. Patients were treated with R-CHOP21 x 3 (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 day 1 and prednisone 100 mg days 1 – 5). Stem cells were harvested after high dose Ara-C x 1 (2g/m2 BID days 1 – 4), followed by rituximab on day 11 for in vivo purging and G- CSF. After haematological recovery BEAM conditioning (carmustine 300mg/m2 day 1, Ara-C 200mg/m2 and etoposide 200 mg/m2 days 2 – 5 and melphalan 2 x 100 mg/m2 day 6) was given with autologous stem cell support day 8). After 3 x R-CHOP 17 patients did not reach PR and went off study, according to the protocol, and 5 patients were excluded for other reasons. Sixty four patients received HD Ara-C and 63 patients proceeded to BEAM. Haematological toxicity was as follows: the median time of recovery of leukocytes (> 1,0 x 109/l) from start of high dose Ara-C was 17 days (range: 0 – 59 days), from start of BEAM 26 days (range: 17 – 55). For platelets the median time to recovery (> 50 x 109/l) from start of high dose Ara-C was 23 days (range: 0 – 44 days) and from start of BEAM 25 days (range: 16 – 364). Non-hematological toxicity grade 3–4 was seen during CHOP in 13%, after HD Ara-C in 20%, mainly gastro-intestinal, and after BEAM in 51%, mainly gastro-intestinal and liver, of the patients. Grade 3–4 infections were seen during CHOP in 17%, after HD Ara-C in 30% and after BEAM in 59% of the patients. Responses to treatment are summarised in Table 1. At two years FFS was 67%, OS was 81%. An analysis restricted to the 63 patients who completed the protocol treatment showed FFS 90% and OS 98% at two years. We conclude that intensification of first line treatment with rituximab, HD Ara-C and BEAM is beneficial with respect to FFS and OS in younger MCL patients and that this regimen is well tolerated. Table 1. Response to treatment N CR PR NR/PD Not yet known after 3x CHOP 83 13 (16%) 51 (61%) 17 (20%) 2 after HD Ara-C 64 22 (34%) 28 (44%) 14 after BEAM 63 43 (68%) 13 (21%) 7 died early 1


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