Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality

This study investigated the use of a nonablative conditioning regimen to de crease toxicity and achieve engraftment of an allogeneic blood stem cell tr ansplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prio r response to conventional chemotherapy. Patients received a preparative re gimen of fludarabine (25 mg/m(2) given daily for 5 days or 30 mg/m(2) daily for 3 days) and intravenous cyclophosphamide (1 g/m(2) given daily for 2 d ays or 750 mg/m(2) daily for 3 days). Nine patients received rituximab in a ddition to the chemotherapy. Tacrolimus and methotrexate were used for graf t-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; the ir median age was 51 years. Twelve were in complete remission (CR) at trans plantation. All patients achieved engraftment of donor cells. The median nu mber of days with severe neutropenia was 6. Only 2 patients required more t han one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than gra de IL All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being al ive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by all ogeneic stem cell transplantation is a promising therapy for indolent lymph oma with minimal toxicity and myelosuppression. Further studies are warrant ed to compare nonablative allogeneic hematopoietic transplantation with alt ernative treatment strategies. (C) 2001 by The American Society of Hematolo gy.