scholarly journals Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma

Author(s):  
Jorge E. Romaguera ◽  
Luis E. Fayad ◽  
Lei Feng ◽  
Kimberly Hartig ◽  
Pamela Weaver ◽  
...  
1998 ◽  
Vol 16 (12) ◽  
pp. 3803-3809 ◽  
Author(s):  
I F Khouri ◽  
J Romaguera ◽  
H Kantarjian ◽  
J L Palmer ◽  
W C Pugh ◽  
...  

PURPOSE Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.


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.


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 ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3050-3050 ◽  
Author(s):  
Francesco Merli ◽  
Stefano Luminari ◽  
Fiorella Ilariucci ◽  
Caterina Stelitano ◽  
Mario Petrini ◽  
...  

Abstract BACKGROUND. Rituximab plus HyperCVAD alternating with High Dose Methotrexate and Cytarabine (R-HCVAD) has been tested in patients with newly diagnosed Mantle Cell Lymphoma (MCL) with promising results (Romaguera et al. JCO 2005). In 2005 the Gruppo Italiano Studio Linfomi (GISL) started a phase II multicenter study investigating clinical activity and toxicity of R-HCVAD in a similar group of patients. PATIENTS AND METHODS. To be included in the trial patients must have histologically confirmed diagnosis of MCL, be younger than 70 years, have adequate organ function. Chemotherapy consisted of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicine, and dexamethasone(considered one cycle) alternating every 21 days with rituximab plus high dose methotrexate-cytarabine (considered one cycle) for a total of eight cycles per the MD Anderson protocol. Patients with baseline PCR positivity for t(11;14) on bone marrow (BM) had to perform PCR assessment of BM at evaluation of response and during follow-up. Only patients achieving partial response (PR) were to be addressed to HDC followed by ASCT. RESULTS. Thirty-two patients were enrolled. There were 23 males and 9 females; median age was 54 yrs (29 to 66), 80% were in stage IV, 50% and 71% had Gastrointestinal (GI) and BM involvement, respectively; PCR for t(11;14) was positive on BM in 51% of cases. Seven patients did not complete treatment due to toxicity; of these, two patients died (one with septic shock at cycle 1, one with pulmonary aspergillosis at cycle 4), one patient had thrombosis of central line extended to right atrium at cycle 1, one had grade IV skin reaction at cycle 3, one had a severe pneumonia at cycle 1, two had persistent grade IV hematological toxicity after cycle 1 and 5, respectively. All patients had grade III–IV hematological toxicity. Response was assessed in 17 patients with 16 CR and 1 PR. PCR for t(11;14) negativity on BM was achieved in 4/9 patients after cycle 4 and in 8/9 after cycle 8. After a median follow-up of 24 months 1 patient progressed at 6 months and 1 patient relapsed after 26 months of follow-up. Two-year Failure Free Survival (FFS) was 75% (IC95% 53 to 87) and 2 year Disease Free Survival was 93%(IC95% 59–99). CONCLUSIONS. Though longer follow-up is needed R-HCVAD regimen used in our multicenter setting confirmed high efficacy in terms of response (both clinical and molecular) and FFS. However the regimen was associated to a severe toxicity profile that caused treatment discontinuation in several patients and that may limit its use in the clinical setting.


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

2019 ◽  
Vol 26 (2) ◽  
pp. 273-278
Author(s):  
Merih K Çakar ◽  
Emre Tekgündüz ◽  
Mehmet S Dal ◽  
Alparslan Merdin ◽  
Semih Başçı ◽  
...  

IntroductionThe aim of this study was to investigate the influence of high-dose cytosine arabinoside (HDAC)-containing treatments followed by autologous hematopoietic stem cell transplantation on the survival of patients with mantle cell lymphoma.Material and methodsThe data of 27 MCL patients who were followed-up between January 2009 and December 2015 were analyzed retrospectively.ResultsThe median age of the patients was 63 (range, 45–82) with 22 (81.4%) males and 5 (18.6%) females. Eight of 27 patients were treated with HDAC-containing regimens either as induction or salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT). The patients who received HDAC-containing regimen followed by AHSCT were found to have better one-year survival compared to others ( p = 0.03). Median follow-up of patient cohort was 27.6 months and median overall survival (OS) was not reached. The probability of one-year OS for all patients was 76.8%.ConclusionOur findings suggest that HDAC treatment followed by AHSCT seems to provide the best outcome for young-fit patients presenting with mantle cell lymphoma.


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