Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyl-lysophospholipid.
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 micrograms/mL of edelfosine. There were 9 lymphoblastic and 15 myelogenous leukemia patients. The median time to granulocyte recovery to 500/microL was 26 and 33 days for the 50 and 75 microgram/mL doses, respectively. The patient whose marrow was purged at the dose of 100 micrograms/mL failed to engraft. The median time to platelet recovery to 25,000/microL was 45 and 37 days for the 50 and 75 micrograms/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 micrograms/mL of edelfosine is a safe dose and is recommended for a phase II trial.
Vogler
W R
WR
Department of Medicine, Emory University School of Medicine, Atlanta, GA.
Berdel
W E
WE
Olson
A C
AC
Winton
E F
EF
Heffner
L T
LT
Gordon
D S
DS
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000502:physiology; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D015925:Cryopreservation; D005260:Female; D006098:Granulocytes / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000601:surgery*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010742:Phospholipid Ethers / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D015996:Survival Rate; D013997:Time Factors
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; C026659:edelfosine