First Line Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma (MCL).

Despite recent progress in treatment, MCL remains associated with a poor outcome demonstrating a continuous pattern of relapse. In 2002, we initiated a pilot study investigating the feasibility of allogeneic stem cell transplantation (SCT) as part of first line therapy for MCL. The results of the same approach done as part of second line treatment are also reviewed.

Newly diagnosed MCL patients referred to our center were offered participation in a tandem approach therapy. First line treatment consisted of 6 to 8 cycles of R-CHOP chemotherapy. Chemotherapy sensitive patients then underwent stem cell collection and were treated with high dose BEAM chemotherapy and autologous SCT. At day +100 post autologous SCT, consenting patients with an HLA identical sibling received out-patient non-myeloablative (NMA) stem cell transplantation with fludarabine and cyclophosphamide as conditioning regimen and tacrolimus + MMF based graft-versus-host disease (GVHD) prophylaxis. An unrelated donor search was initiated for patients younger then 50 years old. Patients with chemotherapy refractory or recurrent disease were proposed second line salvage chemotherapy. Chemotherapy sensitive patients in this group underwent a tandem approach as part of their salvage treatment and chemotherapy resistant patients received a standard myeloablative SCT with Cy-TBI or Bu-Cy conditioning.

A total of 33 patients referred to our center with MCL received a stem cell transplant. 21 received an allogeneic SCT, of which 14 patients underwent NMA SCT and 7 standard myeloablative (MA) SCT while 12 received a single autologous SCT,16 patients were evaluated for first line tandem approach while 17 were referred for relapsed or resistant disease. 11/16 newly diagnosed MCL patients with a median age of 53, underwent an allogeneic SCT as part of their first line treatment while 5/16 median age 57, did not, lacking a compatible sibling or suitable unrelated donor and were treated with an autologous SCT after R-CHOP chemotherapy. With a median follow-up (FU) of 43 months from SCT (7/11) 64% patients receiving an allogeneic SCT (8 NMA and 3 MA) as part of their first line therapy are alive and free of disease while (4/11) patients respectively died (3 NMA and 1 MA) at 8, 12, 24 and 48 months post allo-SCT from TRM (3/4) or recurrent disease (1/4). Of the 17 patients referred for recurrent or refractory disease, 10/17 median age 52, received an allogeneic SCT. 6/10 received a NMA SCT while 4/10 received a standard myeloablative SCT. With a median FU of 42 months, 60% of patients receiving an allogeneic SCT as part of salvage therapy are alive and disease free. 5/6 patients receiving NMA SCT for resistant or recurrent disease are still alive and disease free while only one patient treated with myeloablative SCT is alive and disease free 87 months post transplant. While (4/10) patients died at 6, 7, 15 and 16 months post transplant (3/4) from TRM and (1/4) from relapse. Long term disease control was strongly associated with the development of chronic GVHD (86%). As expected and despite a shorter FU time of 22 months, relapse (33%) was the major cause of treatment failure after autologous SCT while TRM (28%) was the major cause of treatment failure post allogeneic SCT. NMA allogeneic SCT was associated with an estimated 1 year TRM of 10% and should be the modality selected in chemosensitive patients while the prevention and treatment of GVHD remains an important challenge.

Despite the small sample size and short FU period, allogeneic SCT offers a promising approach to first line treatment of MCL. It should still be viewed as investigational and proposed as part of a larger prospective study. When applied to resistant or recurrent disease, allogeneic SCT remains an effective modality of treatment associated with acceptable toxicity in a rather incurable disease and should be considered the standard approach.

No relevant conflicts of interest to declare.