Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyl-lysophospholipid

Abstract

Alkyl-lysophospholipids are anticancer agents that are selectively toxic to leukemic cells and relatively sparing of normal bone marrow cells. Thus, they would be likely candidates for purging remission marrows before autologous bone marrow transplant. One of the more promising agents is edelfosine, which could be safely used for purging without prolonging marrow recovery. Assays for marrow progenitor cells were performed before and after purging and cryopreservation in 64 patients. There was no significant reduction in colony formation after purging when compared with unpurged cryopreserved marrow, but there was a significant reduction after cryopreservation. Twenty-four patients with acute leukemia in second (16 patients) or third remission (3 patients), early relapse (3 patients), or in first remission with successfully treated extramedullary relapse (2 patients) received marrow-ablative chemotherapy and total body irradiation followed by infusion of marrow purged for 4 hours with 50 to 100 μg/mL of edelfosine. There were 9 lymphoblastic and 15 myelogenous leukemia patients. The median time to granulocyte recovery to 500/ μL was 26 and 33 days for the 50 and 75 μg/mL doses, respectively. The patient whose marrow was purged at the dose of 100 μg/mL failed to engraft. The median time to platelet recovery to 25,000/ μL was 45 and 37 days for the 50 and 75 μg/mL doses, respectively. Twenty-nine percent of the patients remain disease free from 131 to 1,291 days, with a median of 356 days. These results have established that purging with 75 μg/mL of edelfosine is a safe dose and is recommended for a phase II trial. © 1992 by The American Society of Hematology.