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. The median time from disease diagnosis to HCT was 2.8 (range 0.4 to 9.5) years. The median number of prior treatment regimens was 4 (range 1 to 10). Recipients of unrelated grafts were more heavily pretreated than those of related grafts (median treatment regimens 5 versus 3, respectively). Forty-two percent (10/17 unrelated recipients versus 4/16 sibling recipients) of patients had failed autologous HCT. Thirty-nine percent of patients were refractory to salvage chemotherapy or planned autologous HCT. Forty-one percent of the unrelated recipients had moderate to large disease burdens compared to 25% of the related recipients. The median follow-up after HCT for surviving patients was 24.6 (range 2.7 to 41.7) months. Thirty-one of the 33 patients had stable engraftment, while 2 patients experienced non-fatal graft rejections. The incidences of acute grades II, III and IV, and chronic 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)], while 3 patients had progressive disease. Only 1 of the 17 patients who responded and none of the 13 transplanted in CR had disease relapse with a median follow-up of 24.6 months. Relapse and non-relapse 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. On univariate analysis, patients less than 55 years old had worse non-relapse mortality compared to patients who were older than 55 years (p=0.003), b2 microglobulin level greater than the median of 1.85 predicted worse survival (p=0.03), and preceding chemotherapy regimens > 4 predicted a higher risk of relapse. In the time-dependent analysis of the relationship of disease response with GVHD, there was no association between disease response and acute grades I-IV acute GVHD (p=0.36), but a trend was observed with chronic extensive GVHD (p=0.09). 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.
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