Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma

Abstract

We carried out HLA-matched related (n ‫؍‬ 16) and unrelated (n ‫؍‬ 17) hematopoietic cell transplantation (HCT) in 33 patients with relapsed and refractory mantle cell lymphoma after nonmyeloablative conditioning with fludarabine and 2 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Fourteen patients had failed high-dose autologous HCT. Of the 33 patients studied, 31 had stable engraftment, whereas 2 patients experienced nonfatal graft rejections. The incidences of acute grades II, III, and IV, and chronic graft-versus-host disease (GVHD) were 27%, 17%, 13%, and 64%, respectively. The overall response rate in the 20 patients with measurable disease at the time of HCT was 85% (n ‫؍‬ 17; 75% complete remissions [CR] and 10% partial remissions [PR]), whereas 3 patients had progressive disease. Only one of the 17 patients who responded and none of the 13 who received transplants in CR had disease relapse with a median follow-up of 24.6 months. Relapse and nonrelapse mortalities were 9% and 24%, respectively, at 2 years. The Kaplan-Meier probabilities of overall and disease-free survivals at 2 years were 65% and 60%, respectively. Allogeneic HCT after nonmyeloablative conditioning is a promising salvage strategy for patients with relapsed and refractory mantle cell lymphoma. The high response and low relapse rates with this approach suggest that mantle cell lymphoma is susceptible to graft-versus-tumor responses. (Blood.

Tacrolimus and mycofenolate mofetil as GvHD prophylaxis following nonmyeloablative conditioning and unrelated hematopoietic SCT for adult patients with advanced hematologic diseases

“…[10][11][12][13]31,32 The long-term results observed in our patients who failed to achieve remission before NM conditioning are poor, with a corresponding 3-year OS probability of 20%, which is significantly lower than the 59% for patients treated in remission.…”

“…7,8 This dilemma is most significant in patients with previous treatment failure or refractory disease, and becomes more important due to an increased usage of NM allo-transplants as final salvage strategy for patients with advanced or active disease. [9][10][11][12][13][14] Traditionally, a combination of CsA and mycophenolate mofetil (MMF) has been used as GvHD prophylaxis in the context of fludarabine/2 Gy TBI allografting, a NM regimen developed by Storb and colleagues in Seattle. 15,16,17 In 2005, Nieto et al 18 observed low rates of early-onset aGvHD in 32 patients receiving matched-sibling transplants, after conditioning with fludarabine/TBI using a combination of tacrolimus and MMF as GvHD prophylaxis.…”

Long-term progression-free survival after early autologous transplantation for mantle-cell lymphoma

“…26 Furthermore, reduced-intensity conditioning regimens allow allogeneic transplantation of a broader group of patients, and available data suggest that durable responses may be achieved in a substantial proportion of patients with relapsed or refractory MCL, suggesting that MCL is subject to potent GVL effects. 14,[27][28][29][30] Historically, MCL has been characterized by relatively brief remissions and short survival times relative to other non-Hodgkin's lymphoma subtypes. The developments of more aggressive induction chemotherapy regimens and monoclonal antibody therapy and advances in both transplantation and supportive care have improved the outlook for patients with MCL.…”

Mantle Cell Lymphoma: Decision Making for Transplant

“…In the allogeneic transplant setting, benefit of cure over transplant related mortality can be positively affected by using reduced intensity (RIC) or non-myeloablative (NMA) conditioning regimens [105][106][107][108][109][110][111][112][113][114][115][116] . Using donor lymphocyte infusions for GVL effect in patients undergoing allogeneic transplantation with RIC or NMA regimens, low transplant mortality rates (<10%) and higher OS (73 to 85%) and EFS rates (73 to 82%) can be achieved 105,117,118 .…”