High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3158-3162 ◽  
Author(s):  
Ajay K. Gopal ◽  
Joseph G. Rajendran ◽  
Stephen H. Petersdorf ◽  
David G. Maloney ◽  
Janet F. Eary ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Remission Rate ◽  
Disease Free Survival ◽  
High Dose ◽  
Specific Monoclonal Antibody ◽  
Free Survival ◽  
Mantle Cell

Abstract Relapsed mantle cell lymphoma is a radiation-sensitive malignancy that is unlikely to be cured by treatment with conventional high-dose therapy and autologous stem cell transplantation. We tested the safety and efficacy of using a CD20-specific monoclonal antibody conjugated with 131I to deliver high-dose radiation selectively to all lymphoma sites. Patients with relapsed or refractory mantle cell lymphoma received infusions of 131I-labeled CD20-specific monoclonal antibody (Tositumomab). The antibody dose was 1.7 mg/kg body weight, and the amount of 131I was calibrated to deliver 20 to 25 Gy to vital normal organs. This treatment was followed 10 days later by administration of high-dose etoposide (30-60 mg/kg), cyclophosphamide (60-100 mg/kg), and infusion of cryopreserved autologous stem cells. The 16 patients in this study had received a median of 3 prior treatments, and 7 had chemotherapy-resistant disease. The median dose of 131I was 510 mCi (18.87 GBq). There were no therapy-related deaths. Among the 11 patients with conventionally measurable disease at the time of treatment, the respective complete and overall response rates were 91% and 100%. Fifteen patients remain alive, and 12 have had no progression of lymphoma at 6 to 57 months from transplantation and 16 to 97 months from diagnosis. Overall survival at 3 years from transplantation is estimated at 93%, and progression-free survival is estimated at 61%. High-dose treatment with 131I-Tositumomab, etoposide, and cyclophosphamide results in a high remission rate and may provide long-term disease-free survival for patients with relapsed or refractory mantle cell lymphoma.

Rituximab and Stem Cell Transplantation Produces Durable Remissions in Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1390-1390
Author(s):  
Francisco J. Capote ◽  
M. J. Pascual ◽  
E. Gonzalez-Barca ◽  
J. M. Bergua ◽  
A. Jimenez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell

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.

Nordic Mantle Cell Lymphoma (MCL) Project: Preemptive Rituximab Treatment of Molecular Relapse Following Autotransplant Can Reinduce Molecular Remission and Prolonged Disease-Free Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2429-2429
Author(s):  
Christian H. Geisler ◽  
Erkki Elonen ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Lone B. Pedersen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
High Dose ◽  
Clinical Relapse ◽  
Relapse Free Survival ◽  
Molecular Remission ◽  
Free Survival ◽  
Mantle Cell ◽  
Disease Free

Abstract The 2nd. Nordic Lymphoma Group mantle cell lymphoma (MCL2) protocol has demonstrated the importance of Ara-C and Rituximab in the induction chemotherapy and stem-cell mobilisation before high-dose therapy and autologous stem-cell transplant (1). By July 2005, 128 patients (83% stage IV) had completed protocol treatment consisting of 3 series of R-CHOP and 3 series of R-Ara-C, stem-cell harvest and high-dose therapy with BEAM/BEAC with ASCT. The 5-year failure-free and overall survival is 50% and 83% respectively, significantly higher than the historic control group of the Nordic MCL1 protocol with the same treatment without HD-Ara-C and Rituximab (P&lt;0.0001). Patients with a molecular marker (t(11;14) or clonal IgH rearrangement) identified at the time of diagnosis in bone marrow and blood, undergo regular molecular follow-up posttransplant,. Patients who turn PCR-positive or increase their qPCR signal, without clinical disease, are offered preemptive treatment with Rituximab 375 mg/m2 Wx4. Of 75 patients with molecular markers who had completed treatment, 55 remain PCR-negative and 20 have become/remained PCR-pos. posttransplant. Clinical relapse ocurred significantly more often in the latter group (11 of 20) than in the PCR-neg. patients (4 of 55) (P&lt;0.0001) (Fig.1). Ten of the 20 PCR-positive patient did not receive preemptive rituximab: five due to immediate clinical relapse, 2 due to stable qPCR signals, one due to protocol error and two await treatment. Of 10 patients who did receive preemptive rituximab 8 again became PCR-negative and 2 remain PCR-positive. Six of the 10 Rituximab treated patients remain in clinical and molecular remission 200–600 days after the Rituximab treatment (Fig. 2). Conclusions: In MCL, molecular relapse is a harbinger of imminent clinical relapse, whereas continuous molecular remission is associated with prolonged disease-free survival (89% at 4 years) Rituximab preemptive treatment can reinduce molecular remission and may delay clinical relapse. Following molecular relapse, only Rituximab treated patients (6 of 8 evaluable) remain disease-free. FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE. FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE.

A Retrospective Analysis of Mantle Cell Lymphoma Patients Series Treated Upfront by Sequential High Dose Immunochemotherapy Supported by In Vivo Purged Stem Celle Double Autologous Transplantation: A Monocentric Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4949-4949
Author(s):  
Andrea Ferrario ◽  
Giorgia Saporiti ◽  
Nicola Orofino ◽  
Francesco Onida ◽  
Daniele Vincenti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
Standard Dose ◽  
Autologous Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell ◽  
High Dose Cytarabine ◽  
Disease Free

Abstract Abstract 4949 Mantle Cell Lymphoma (MCL) is a rare lymphoma that accounts for 3–10% of all non Hodgkin's Lymphoma in adults. Being associated with rapid progression and high recurrence rate, although some treatment improvements during the last years, it is still considered an incurable disease. In order to overcome the poor outcome obtained with conventional chemotherapy, new treatment strategies using high dose chemotherapy supported by autologous stem cell transplantation (ASCT) have been developed in young patients. In particular the use of high dose cytarabine and rituximab prior to ASCT has been demonstrated to improve outcome in terms of response and disease free survival. The present study is a restrospective analysis conducted in our centre in order to evaluate the outcome of 16 MCL patients treated upfront with sequential high dose immunochemotherapy followed by double ASCT. From 2000 to 2011, 16 MCL patients, eligible for ASCT, have been consecutively treated as follow: a) standard dose phase: APO: doxorubicin, 75 mg/sqm i.v., day 1; prednisone, 60 mg/sqm orally, day 1 to 5 and day 9 to 12; vincristine, 1.4 mg/sqm i.v., day 1 and 8; DHAP: cisplatin 70 mg/sqm, day 1; cytarabin 1500 mg/sqm i.v., days 2–3; dexametasone 40 mg i.v., days 1 to 3; b) rituximab high dose sequence: high dose cyclophosphamide (CTX 5 g/sqm) and high dose cytarabine (Ara-C 2 g/sqm every 12 hours for 6 consecutive days) followed by peripheral blood stem cell (PBSCs) collection; c) high dose melphalan (180 mg/sqm) and high dose mitoxantrone plus melphalan (60 mg/sqm and 180 mg/sqm, respectively) followed by PBSCs infusion. Rituximab (375 mg/sqm) was infused twice after CTX, cytarabine and double autologous transplantation (modified from Gianni et al, Blood, 102, 749, 2003). All patients (9 female and 7 male) had a histological diagnosis of MCL according to the WHO classification criteria; molecular rearrangement of bcl-1 locus was detected by PCR in the bone marrow of 8 patients. The median age at diagnosis was 57 years (range 50–68); 14 patients were in stage IV and 2 in stage III; 2 patients had bulky disease at presentation. Four patients were in overt leukemic phase and 2 had extranodal localization. According to MIPI score, 14 patients (87%) were classified as low risk and 2 (13%) as intermediate risk. Double transplant was performed in all patients except one (who refused it). The standard dose phase, including a median number of 4 cycles (range 3–5), was generally well tolerated, with only one patient experiencing tumor lysis syndrome. After induction, clinical CR was achieved in six patients. PBSCs were successfully collected after both the CTX/rituximab (1.8-9.7×10̂6/Kg) and the Ara-C/rituximab (7.1- 40.0×10̂6/Kg) cycles. At the end of these phases, 7 patients (44%) were in CR while 9 (56%) were in PR. Following transplants, median times to ANC >500/μL were 11 days (range 10–14) in both the procedures, whereas median times to platelet recovery (>50000/μL) were 19 days (range 10–44) after the first transplant and 24 days (range 11–298) after the second one. After a median follow-up of 38 months (range 14–111), 10 patients (62%) were alive (8 in CR, 2 in relapse), whereas 6 died from disease progression. Our study confirmed that in MCL the use of sequential high dose immunochemotherapy including rituximab and high dose cytarabine followed by double autologous transplantation is associated to high remission rates with long-term disease-free survival in a significant proportion of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Beac and BEAM High-Dose Chemotherapy in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation Are Efficacious, with Comparable Toxicity

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5828-5828
Author(s):  
Noa Lavi ◽  
Ron Ram ◽  
Odelia Amit ◽  
Netanel A Horowitz ◽  
Tzila Zuckerman
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell

Abstract Introduction: Autologous stem cell transplantation (ASCT) is currently considered the standard first-line consolidation therapy for younger patients with mantle cell lymphoma (MCL). In general, there are limited data regarding a preferred high-dose therapy (HDT) regimen preceding ASCT to be used in patients with non-Hodgkin lymphoma (NHL). Although BEAM and BEAC regimens (including BCNU, etoposide, cytosar in both regimens and melphalan or cytoxan, respectively) have been commonly employed as conditioning HDT in patients with aggressive or recurrent NHL, there have been few reports comparing these two regimens. A retrospective analysis found the superiority of BEAM over BEAC in terms of overall survival (OS) and event-free survival (EFS). Regimen-related toxicities were similar, except that BEAM was associated with more frequent lower gastrointestinal mucositis. Other studies reported that these two regimens had equivalent efficacy and outcome, as measured by EFS and OS. Further studies are required to define the optimal regimen for each specific NHL subtype. The current study aimed to compare the efficacy and toxicity of BEAC versus BEAM as a consolidation HDT in young patients with MCL undergoing ASCT. Methods: This is a retrospective analysis of outcomes in patients with MCL who received high-dose chemotherapy with BEAM or BEAC regimen followed by ASCT in two bone marrow transplant centers in Israel. OS, progression-free-survival (PFS) and regimen toxicity were compared. Results: Fifty five patients with MCL who were diagnosed between 1995-1/2016 and received consolidation with BEAC or BEAM HDT regimen were included in the analysis. Twenty seven patients were treated with BEAM and 28 patients - with BEAC. No significant differences between the two groups were revealed in terms of age, sex, the Mantle Cell Lymphoma International Prognostic Index (MIPI), induction treatment protocol and percentage of patients who were transplanted at first complete response (CR1) (Table 1). The amount of infused CD34 cells was significantly higher in the BEAM group, and the number of days until platelet engraftment was significantly greater in the BEAC group. There were no differences in the number of blood transfusions or hospitalization days between the groups (Table 2). In terms of HDT toxicity, there was a trend to a higher rate of grade 3-4 upper mucositis with BEAM protocol; no other differences in toxicity between the regimens were observed (Table 3). Non-relapse mortality at day 30 post-transplant was 0% in both groups. A median follow-up of surviving patients was 31 (range 1-119) months. PFS at 3 years in patients receiving BEAM and BEAC was 65% and 78%, respectively (p=.75). In univariate analysis, age less than 60 years, low-to-intermediate MIPI and transplant at CR1 were found to significantly improve PFS, while no difference in PFS was found between the two treatment regimens. In multivariate analysis, low-to-intermediate MIPI and transplant at CR1 appeared to significantly increase PFS (P = 0.02 and 0.03, respectively). There was no difference in the 3-year OS between the two HDT regimens (58% in the BEAM group and 81% in the BEAC groups; p=.31). Conclusion: BEAC and BEAM high dose chemotherapy regimens followed by autologous stem cell transplantation have similar efficacy and toxicity in patients with MCL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-term disease-free survival of patients with advanced mantle-cell lymphoma following high-dose chemotherapy

1998 ◽  
Vol 21 (1) ◽  
pp. 55-57 ◽  
Author(s):  
N Kröger ◽  
M Hoffknecht ◽  
P Dreger ◽  
W Krüger ◽  
W Zeller ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell ◽  
Disease Free

scholarly journals Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome After High-Dose Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2558
Author(s):  
Malte Roerden ◽  
Stefan Wirths ◽  
Martin Sökler ◽  
Wolfgang A. Bethge ◽  
Wichard Vogel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Clinical Decision Making ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Mantle Cell ◽  
Autologous Grafts

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.

1998 ◽  
Vol 16 (12) ◽  
pp. 3803-3809 ◽  
Author(s):  
I F Khouri ◽  
J Romaguera ◽  
H Kantarjian ◽  
J L Palmer ◽  
W C Pugh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Mantle Cell ◽  
Previously Treated

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.

scholarly journals Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas – a single centre experience

2016 ◽  
Vol 51 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Lucka Boltezar ◽  
Karlo Pintaric ◽  
Jože Pretnar ◽  
Maja Pohar Perme ◽  
Barbara Jezersek Novakovic
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Treatment ◽  
Mantle Cell

Abstract Background Advanced follicular lymphoma (FL) and mantle cell lymphoma (MCL) are incurable diseases with conventional treatment. The high dose treatment (HDT) with autologous stem cell transplantation (ASCT), however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS) and overall survival (OS) in patients with FL and MCL treated with ASCT. Patients and methods Seventeen patients with FL and 29 patients with MCL were included, 15 of them were transplanted to consolidate the response to second line treatment and 24 to consolidate their first remission, respectively. All were conditioned with total body irradiation (TBI) and high dose cyclophosphamide between 2006 and 2014 and all were transplanted with peripheral blood stem cells. Results The estimated 5-year OS for FL was 87.8% (95% confidence interval [CI] 59.5%–96.8%) and for MCL 79.3% (95% CI 56.1%–91.1%), respectively. The estimated 5-year EFS for FL was 76.0% (95% CI 48.0%–90.3%) and for MCL 69.8% (95% CI 45.5%–84.8%), respectively. There were no secondary hematological malignancies observed in either group. Conclusions Based on above results, the ASCT with TBI is a good treatment option in terms of long-term survival for patients with follicular and mantle cell lymphoma demonstrating a relatively low rate of late toxicities and secondary malignancies.

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