Faculty Opinions recommendation of Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years.

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>1 6%, LDH > 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.

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Autologous Stem Cell Transplantation and Rituximab for Mantle Cell Lymphoma.

Blood ◽

10.1182/blood.v106.11.2092.2092 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2092-2092

Author(s):

Francisco Javier Capote ◽

E. González-Barca ◽

J.M. Bergua ◽

M.J. Pascual ◽

R. García-Boyero ◽

...

Keyword(s):

Stem Cell ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Mantle Cell Lymphoma ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Cell Lymphoma ◽

High Dose ◽

Mantle Cell

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.

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Rituximab Improves the Outcome of Upfront Autologous Stem Cell Transplantation in Mantle Cell Lymphoma: A Comparison of Different Strategies.

Blood ◽

10.1182/blood.v110.11.5106.5106 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5106-5106

Author(s):

Michael Rieger ◽

Mathias Witzens-Harig ◽

Manfred Hensel ◽

Baerbel Seyfarth ◽

Maike Nickelsen ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Mantle Cell Lymphoma ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Cell Lymphoma ◽

First Line ◽

Rituximab Maintenance ◽

Mantle Cell

Abstract Introduction: First-line autologous stem cell transplantation (SCT) is an accepted therapy for mantle cell lymphoma (MCL). We have recently shown that 2 standard doses of rituximab significantly improve the outcome of TBI-based upfront SCT in MCL when administered peritransplant (Haematologica 92:42; 2007). The purpose of the present retrospective analysis was to compare this approach with alternative rituximab-based strategies. Patients and treatment strategies: 34 consecutive patients treated in KI-HH received 3–6 cycles of CHOP prior to stem cell mobilization with Dexa-BEAM (n=20) or DHAP (n=14), followed by TBI-cyclophosphamide-rituximab myeloablation and SCT (CHOP/R-TBI-CY group). Patients treated in HD received 3–8 cycles of R-CHOP for cytoreduction (n=28) and mobilization (n=23; the remaining 5 patients were mobilized with R-DHAP/HAM) followed by BEAM and SCT (R-CHOP/BEAM group). 12 patients of this group received additional rituximab maintenance after SCT. Results: With a median follow-up of 38 months (9–111), estimated 4-year progression-free survival (PFS) from diagnosis of patients treated with CHOP/R-TBI-CY and R-CHOP/BEAM was 83% and 72% (log rank, p=.38), respectively. Of note, with a median follow-up of 30 months (14–57) there was no relapse in the 12 pts receiving maintenance therapy with rituximab, translating into a significantly better 4-y PFS in patients receiving R-CHOP/BEAM with rituximab maintenance vs those without (100% vs. 56%; p=.021). The PFS difference between the R-CHOP/BEAM group and the CHOP/R-TBI-CY group became borderline significant after omitting the rituximab maintenance patients (p=.055). Conclusions: In advanced-stage MCL, addition of rituximab improves disease control provided by first-line SCT. Whereas the exact dose and timing of rituximab administration remains to be settled, prospective investigation of post-transplant rituximab maintenance appears to be particularly promising.

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