Prognostic Significance of Positron Emission Tomography (FDG-PET) at Baseline and After 4 Cycles of R-CHOP in 75 Patients with Mantle Cell Lymphoma Treated with Intensive Chemotherapy and Autologous Stem Cell Rescue.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1226-1226 ◽  
Author(s):  
Rony Schaffel ◽  
Craig H. Moskowitz ◽  
Jocelyn C. Maragulia ◽  
Carol S. Portlock ◽  
Cyrus V. Hedvat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
Sequential Therapy ◽  
Proliferation Index ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Mantle Cell ◽  
Autologous Stem Cell Rescue

Abstract Abstract 1226 Poster Board I-248 Background The value of FDG-PET in mantle cell lymphoma (MCL) has not been addressed in a homogeneous group of pts. The optimal initial therapy is controversial; however, intensified therapy followed by consolidation with high-dose therapy and autologous stem cell rescue (HDT-ASCR) is associated with superior progression-free survival (PFS) compared to CHOP-based therapy. In this study, we examined the prognostic value of FDG-PET in a group of uniformly treated pts with upfront HDT-ASCR consolidation. The role of FDG-PET was evaluated: at baseline; as a predictor of proliferation index (PI); and as interim evaluation after induction therapy prior to HDT-ASCR. Pts and Methods Pts received sequential therapy consisting of sequential R-CHOP-14 × 4 followed by RICE x 2-3 cycles and consolidation with HDT-ASCR. FDG-PET and diagnostic CT imaging was obtained at baseline and after R-CHOP (N=75). The number of cycles of RICE was determined by the PET and CT response after induction with R-CHOP-14×4; pts with FDG-avid disease received a third cycle. Additional therapy was administered in 10 pts who had persistent FDG-avid disease after RICE with the objective of achieving the best response prior to the HDT-ASCR. Therapy included bortezomib in 7 cases and other treatment in 3 cases. The PI was determined by quantitative image analysis of Ki-67 stained slides (N=39). The median follow-up was 3.4 years. Results The median age was 59 years, 71% had bone marrow disease and 85% had stage 4 disease. According to the MIPI score, 50% had low-risk, 35% had intermediate-risk and 15% had high-risk disease. The baseline FDG-PET was positive in 71 pts (95%) and the median SUV was 5.5 (1.6-14). The baseline SUV was not prognostic after the stratification of the pts by the median SUV (PFS 81% vs 84% and overall survival (OS) 100% vs 74%, p=0.15). The median PI was 22% for the pts with an SUV below the median and 36% for the other group (P=0.03, Mann-Whitney). Interim FDG-PET evaluation after induction with R-CHOP-14 was available in 69 pts among the 71 with a positive test at baseline, the exam was negative in 49 pts (71%). A negative interim FDG-PET was associated with a better PFS (84% v 40% at 4years, p<0.0001) and a better OS (94% v 70% at 4 years, p=0.019). When FDG-PET results were added to response determined by CT scan, there was no difference in PFS between FDG-PET negative with either a CT CR (N=28) or CT PR (N=20) (91% vs 73% at 4 years, P=0.89). In contrast, patients with a CT PR had an inferior PFS and OS when the FDG-PET was positive (N=19) compared when the FDG-PET was negative (42% vs 76% at 4 years, P=0.008). The 4-year OS was 96% for FDG-PET negative CT CR, 91% for FDG-PET negative CT PR and 70% for FDG-PET positive CT PR (P=0.08). Conclusions In MCL, a baseline FDG-PET is useful as not all cases are positive. Though SUV correlates with the PI, the pretreatment SUV alone is not prognostic. Pts in PR by CT are separated by the FDG-PET result with negative pts having a superior outcome. The interim FDG-PET after induction with R-CHOP-14 × 4 is prognostic for PFS and OS in a program of sequential therapy with upfront consolidation with HDT/ASCR. Disclosures No relevant conflicts of interest to declare.

Sequential Chemotherapy Followed by High Dose Therapy and Autologous Stem Cell Rescue for Mantle Cell Lymphoma: Impact of MIB-1 on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3759-3759
Author(s):  
Andrew D Zelenetz ◽  
Craig Moskowitz ◽  
Jocelyn Maragulia ◽  
Carol S. Portlock ◽  
Julie Teruya-Feldstein
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Sequential Chemotherapy ◽  
Dose Therapy ◽  
Stem Cell Rescue ◽  
Mantle Cell ◽  
Mib 1

Abstract Introduction: Optimal management of mantle cell lymphoma (MCL) remains undefined. However, recent data support the conclusion that upfront consolidation with high dose therapy with autologous stem cell rescue (HDT/ASCR) can improve the PFS (Dreyling, et al., 2005; Geisler, et al., 2008) and possibly OS (Geisler, et al. 2008). Based on gene expression profiling data, the proliferation signature has emerged as a critical determinant of prognosis in MCL (Rosenwald, et al., 2003). Immunohistochemical assessment of proliferation as estimated by MIB-1 (Ki-67) staining has been shown to predict outcome in patients with MCL treated with chemotherapy or immunochemotherapy. With conventional chemotherapy, the reported MIB-1 staining cutoff associated with poor prognosis reportedly varies from 10–30%. Since 1994 we have treated patients (pts) with MCL with sequential chemotherapy followed by HDT/ASCR. The current analysis is a retrospective review of our treatment program focused on the impact of upfront consolidation with HDT/ASCR on the prognostic significance of proliferation as measured by MIB-1 immunohistochemistry. Methods: Seventy-nine patients underwent upfront consolidation with HDT/ASCR for MCL. Fifty-two patients had evaluation of proliferation by MIB-1 immunohistochemistry. MIB-1 expression was estimated visually and assigned a percentage. Patients were binned into quintiles of MIB-1 expression: 0–20% (n=32, 61.5%); 21–40% (n=5, 9.6%); 41–60% (n=5, 9.6%); 61–80% (n=5, 9.6%); and 81–100% (n=5, 9.6%). Outcomes were analyzed by the method of Kaplan-Meier and comparisons were by log-rank. Results: The EFS and OS at 5 years was 65.1% and 61.4% respectively for the subset of patients with available MIB-1 staining (n=52); the outcomes for the entire group (n=79) did not differ from the subset. Outcomes (PFS, OS) were evaluated by MIB-1 quintile with successive cutoff values of 20%, 40%, 60% and 80%. MIB-1 cutoff values of 40% or less were not predictive of outcome. However, when the cutoff was 60% or 80%, both the PFS and OS were significantly worse for the high proliferation group. Nineteen percent of patients had a proliferation fraction of greater than 60%. For patients with MIB-1 staining of >60% the PFS was 4.2 years and was not reached for the group with staining ≤60% (p=0.004). Similarly, overall survival was significantly different, (p=0.031). Conclusions: These findings suggest that upfront consolidation with HDT/ASCR can partially overcome the adverse impact of proliferation on outcome and the adverse outcomes are seen in a subgroup of approximately 20% of patients with MIB-1 staining of greater than 60%.

Mantle Cell Lymphoma

2016 ◽  
Vol 34 (11) ◽  
pp. 1256-1269 ◽  
Author(s):  
Chan Yoon Cheah ◽  
John F. Seymour ◽  
Michael L. Wang
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Kinase Inhibitor ◽  
Cell Lymphoma ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell ◽  
Molecular Pathophysiology

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma previously considered to have a poor prognosis. Large gains were made in the first decade of the new century when clinical trials established the importance of high-dose therapy and autologous stem-cell rescue and high-dose cytarabine in younger patients and the benefits of maintenance rituximab and bendamustine in older patients. In particular, greater depth of understanding of the molecular pathophysiology of MCL has resulted in an explosion of specifically targeted new efficacious agents. In particular, agents recently approved by the Food and Drug Administration include the proteasome inhibitor bortezomib, immunomodulator lenalidomide, and Bruton’s tyrosine kinase inhibitor ibrutinib. We review recent advances in the understanding of MCL biology and outline our recommended approach to therapy, including choice of chemoimmunotherapy, the role of stem-cell transplantation, and mechanism-based targeted therapies, on the basis of a synthesis of the data from published clinical trials.

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.

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.

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