T-cell depletion plus salvage immunotherapy with donor leukocyte infusionsas a strategy to treat chronic-phase chronic myelogenous leukemia patientsundergoing HLA-identical sibling marrow transplantation

T-cell depletion (TCD) of the donor marrow graft has been shown to reduce t he severity of graft-versus-host disease (GVHD) in patients with chronic-ph ase (CP) chronic myelogenous leukemia (CML) undergoing HLA-identical siblin g allogeneic marrow transplantation. However, there has been a correspondin g reduction in the graft versus-leukemia effect so that any decrease in GVH D-related mortality has been offset by an increased rate of disease relapse . Therapy of recurrent disease with donor leukocyte infusions (DLI) has bee n proven to be effective salvage therapy for the majority of patients who r elapse after allogeneic BMI with CP CML, However, the overall impact of sal vage DLI therapy on the survival of CP CML patients initially transplanted with TCD marrow grafts is not defined. To address this question, we have ev aluated a clinical strategy of TCD followed by targeted adoptive immunother apy with DLI in 25 CP CML patients undergoing allogeneic BMT from HLA-ident ical siblings. All patients received a standardized preparative regimen alo ng with ex vivo TCD and posttransplant cyclosporine as GVHD prophylaxis. Du rable engraftment was observed in all 25 patients. The incidence of grade I I to IV acute GVHD was 8%. The cumulative incidence of transplant related m ortality (TRM) was 4%, and the 1-year probability of overall survival was 9 6%, The a-year cumulative relapse incidence was 49%. All relapsed patients received DLI to reinduce remission. The total T-cell dose administered to t hese patients varied from 0.1 to 5.0 x 10(8) T cells/kg, Complete responses were observed in 12 of 14 patients, with 1 additional patient still too ea rly to evaluate. Three patients died of GVHD after DLI, and 1 relapsed into blast crisis after a transient cytogenetic remission. Of the remaining 10 patients, 8 are in molecular remission, 1 is alive in relapse, and 1 is rec eiving DLI treatment. The median follow-up after infusion of surviving DLI patients in remission is 5.3 years, The probability of overall B-year survi val for the entire population is 80%, with a median follow up of 6.4 years. We conclude that the clinical strategy of TCD followed by targeted adoptiv e immunotherapy with DLI for those patients with evidence of recurrent dise ase is a viable transplant strategy for CP CML, resulting in 80% survival a nd a low risk of acute GVHD and transplant-related mortality. (C) 1999 by T he American Society of Hematology.