Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged marrow for acute lymphoblastic leukemia

Abstract

Ten patients age 13-52 years with acute lymphoblastic leukemia (ALL) in first complete remission (CR) (1), second CR (6), or relapse (3) were treated with cyclophosphamide 50 mg/kg daily x 4 and total body irradiation 3 Gy daily x 4 followed by infusion of autologous marrow purged with 4-hydroperoxycyclophosphamide (4-HC) at 100-120 micrograms/ml. The patients transplanted in relapse also received 2 mg vincristine and corticosteroids. All marrows were harvested while patients were in CR. The nucleated marrow cell dose was 3.5 +/- 0.7 x 10(8)/kg, and the CFU-GM content of the transplant was 0.4 +/- 0.5 x 10(3)/kg after purging with 4-HC. Median time from transplantation is 48 months. The neutrophil count (ANC) exceeded 1.0 x 10(9)/L at a median of 26 days and platelets exceeded 50 x 10(9)/L at 34 days. All patients were in remission after transplantation (ABMT). Five patients relapsed 2-9 months after ABMT (actuarial rate 60%). Three patients are alive and in CR at 17+, 43+, and 54+ months after ABMT. Purging marrow with 4-HC did not adversely affect engraftment, but it is not clear if the high relapse rate was due to incomplete ex vivo purging or inadequacy of the conditioning regimen.