Quantitative Assessment of Molecular Remission Following Autologous Stem Cell Transplantation Predicts Long Term Remission in Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3275-3275 ◽  
Author(s):  
Christiane Pott ◽  
Carsten Schrader ◽  
Stefan Gesk ◽  
Lana Harder ◽  
Markus Tiemann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
High Dose ◽  
Negative Group ◽  
Molecular Remission ◽  
Positive Group ◽  
Mantle Cell

Abstract Mantle cell lymphoma (MCL) is characterized by a poor response to cytostatic therapy and a short survival with a median of less than 3 years. High-dose chemotherapy followed by autologous peripheral stem cell transplantation (ASCT) provides a potential curative option for the treatment of younger patients. The prognostic relevance of minimal residual disease (MRD) detection after intensive conventional treatment and high dose therapy has been proven for follicular lymphoma but is still under debate in MCL. Aim of this study was the quantitative evaluation of MRD and the evaluation of its prognostic impact on progression free survival and long-term remission in patients with MCL after ASCT. Quantitative Real-Time PCR for clonal IGH rearrangements (IGH-RQ-PCR) was performed in 29 patients with MCL treated with CHOP-like induction, stem-cell mobilisation with DexaBEAM. and subsequent ASCT. Quantitative MRD assessment was performed prior and during treatment as well as 3,6 and 12 months after PBSCT by IGH-RQ-PCR. 14/27 patients evaluable for MRD after ASCT achieved a complete clinical and molecular remission, whereas 13 patients had detectable MRD within the first year after ASCT. Molecular remission after ASCT was strongly predictive for improved outcome with a median PFS of 95 months in the MRD negative group compared to 21 months in the MRD positive group (p<0.0001). Overall survival differed significantly with 55.8 months in the MRD positive group, whereas median OS of the MRD negative group has not been reached (p<0.003). In multivariate analysis, molecular remission and bulky disease were independent prognostic factors for PFS (p=0.0007 and p=0.0210 respectively). Quantitative MRD measured in the stem cell products of 28 patients was not predictive for achieving molecular remission. We conclude that sequential quantitative monitoring of residual disease after ASCT is a powerful indicator for treatment outcome in MCL and defines subgroups of patients with a significantly different prognosis.

Quantitative assessment of molecular remission after high-dose therapy with autologous stem cell transplantation predicts long-term remission in mantle cell lymphoma

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2271-2278 ◽  
Author(s):  
Christiane Pott ◽  
Carsten Schrader ◽  
Stefan Gesk ◽  
Lana Harder ◽  
Markus Tiemann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
High Dose ◽  
Negative Group ◽  
Molecular Remission ◽  
Positive Group ◽  
Mantle Cell

Abstract To evaluate the prognostic impact of minimal residual disease (MRD), quantitative real-time polymerase chain reaction (RQ-PCR) of clonal IGH rearrangements was performed in 29 patients with mantle cell lymphoma (MCL) treated with high-dose radiochemotherapy and autologous stem cell transplantation (ASCT). Fourteen of 27 patients evaluable for MRD after ASCT achieved complete clinical and molecular remission, whereas 13 patients had detectable MRD within the first year after ASCT. Molecular remission after ASCT was strongly predictive for improved outcome, with a median progression-free survival (PFS) of 92 months in the MRD-negative group compared with 21 months in the MRD-positive group (P < .001). Median overall survival (OS) was 44 months in the MRD-positive group and has not been reached in the MRD-negative group (P < .003). In multivariate analysis, molecular remission and bulky disease were independent prognostic factors for PFS (P = .001 and P = .021, respectively). While cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP)–like cytoreduction had only modest influence, ara-C–containing mobilization and myeloablative radiochemotherapy significantly reduced MRD. Quantitative MRD measured in the stem cell products of 27 patients was not predictive for molecular remission. We conclude that sequential quantitative monitoring of residual disease after ASCT is a powerful indicator for treatment outcome in MCL and defines subgroups of patients with a significantly different prognosis.

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.

Long-term clinical and molecular remissions in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation

2013 ◽  
Vol 93 (5) ◽  
pp. 803-810 ◽  
Author(s):  
Bernd Metzner ◽  
Thomas H. Müller ◽  
Wolfgang Gebauer ◽  
Jochen Casper ◽  
Doris Kraemer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Mantle Cell

scholarly journals Long-Term Results of High-Dose Therapy and Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: Effectiveness of Maintenance Rituximab

2017 ◽  
Vol 23 (11) ◽  
pp. 1861-1869 ◽  
Author(s):  
Matthew G. Mei ◽  
Thai M. Cao ◽  
Lu Chen ◽  
Joo Y. Song ◽  
Tanya Siddiqi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
Long Term Results ◽  
High Dose ◽  
High Dose Therapy ◽  
Mantle Cell

Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma

2009 ◽  
Vol 27 (26) ◽  
pp. 4365-4370 ◽  
Author(s):  
Niels S. Andersen ◽  
Lone B. Pedersen ◽  
Anna Laurell ◽  
Erkki Elonen ◽  
Arne Kolstad ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Clinical Relapse ◽  
Molecular Remission ◽  
Mantle Cell

Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m2 weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.

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.

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.

Long term outcome of patients with mantle cell lymphoma following autologous stem cell transplantation

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 6660-6660
Author(s):  
E. D. Jacobsen ◽  
D. Neuberg ◽  
D. C. Fisher ◽  
L. M. Nadler ◽  
R. J. Soiffer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Mantle Cell
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