Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma

Abstract

In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n ‫؍‬ 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versushost disease. Our results show that longterm disease-free survival in mantle cell lymphoma is possible after rituximabcontaining autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.

The current therapeutic scenario for relapsed mantle cell lymphoma

“…In contrast, considering the low efficacy and the increased toxicity of an auto-SCT approach in second-line [19], such a treatment should be offered only to fit MCL patients who did not receive auto-SCT as first-line. Finally, among palliative approaches for elderly patients, the efficacy, feasibility and low toxicity of an oral low-dose metronomic polichemotherapy combination (PEP-C) is noteworthy, optionally in combination with rituximab and thalidomide [20,21].…”

“…Anderson [19] 35 most-chemosensitive (88%) patients (median age 58 years) received a NMA allo-SCT (fludarabine, cyclophosphamide and high-dose rituximab). A 6-year PFS rate of 46% was reported, with a plateau phase after 3 years and no relapse after 63 months of follow-up, whereas the 6-year overall survival (OS) was 53%.…”

Mantle Cell Lymphoma: Decision Making for Transplant

“…Analysis of this patient group did not reveal a plateau in the survival curve 88 . Addition of rituximab to ASCT regimen leads to better event free survival (EFS) curves in patients with first remission, not affecting progression in patients with relapsed/refractory disease 91 . The R-HDS regimen consisting of high-dose sequential chemotherapy (including intravenous administration of high-dose cyclophosphamide, high-dose cytarabine, highdose melphalan, and high-dose mitoxantrone plus melphalan) and in vivo purging with rituximab resulted in OS and EFS rates at 54 months were 89% and 79%, respectively 96 .…”

“…Multiply relapsed patients will not do well after autologous transplants 91,103 . Best time to perform an autologous transplant is following CR 91, 92, 119, 120 obtained after high-dose therapy with hyperCVAD or HDS regimen, coupled with rituximab 91 , including in vivo purging prior to stem cell collection 81,92,96 . With this approach, patients eligible for these sequential intensive regimens may enjoy long term disease free survival, although cure cannot be achieved 121 .…”

“…Since conventional and dose intense chemotherapy regimens have failed to induce cure or a plateau phase in time to treatment failure curves, high dose therapy with autologous stem cell support have been studied in the relapse setting 88 as well as consolidating complete responses following frontline chemotherapy regimens [88][89][90][91][92][93][94] .…”