title: Phase I study of combination drug purging for autologous bone marrow transplantation.
abstract: In a phase I clinical trial of autologous bone marrow transplantation, we determined the feasibility of ex vivo purging with high concentrations of pharmacologics in combination. Light-density cells isolated from the grafts of 26 patients with acute leukemia or lymphoblastic lymphoma were treated with 4-hydroperoxycyclophosphamide (4-HC; 30 to 60 micrograms/mL), vincristine (Vcr; 1.5 to 3.0 micrograms/mL), and methylprednisolone sodium succinate (MP; 5 mg/mL). All patients received marrow-lethal induction therapy followed by infusion of the treated grafts. Three patients died of transplant-related complications before achieving peripheral blood recovery of greater than 0.5 x 10(9) granulocytes per liter. All other patients achieved this parameter of engraftment at a median of 35 days after marrow infusion. The median time to last platelet transfusion was 45 days. These durations of aplasia were similar to those experienced by other patients receiving density-gradient separated grafts treated with 60 micrograms/mL of 4-HC as a single agent. No patient required infusion of untreated reserve marrow because of engraftment failure. The colony-forming unit-granulocyte macrophage (CFU-GM) content of the grafts after purging predicted these parameters of engraftment. Colony-forming unit-leukemia (CFU-L) cultured from the grafts of 12 of the patients treated for acute lymphoblastic leukemia (ALL) were considerably more sensitive to the combination regimen than to 4-HC alone; the sensitivity of CFU-GM from these patients did not differ between the two regimens. The results of this trial indicate the feasibility of treating autologous bone marrow grafts with high concentrations of pharmacologics in combination. The use of combinations may increase the efficacy of ex vivo purging without increasing the toxicity to normal hematopoietic cells.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, MD.
authors.forename: S D
authors.initials: SD
authors.lastname: Rowley
authors.forename: C B
authors.initials: CB
authors.lastname: Miller
authors.forename: S
authors.initials: S
authors.lastname: Piantadosi
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
authors.forename: G W
authors.initials: GW
authors.lastname: Santos
authors.forename: R J
authors.initials: RJ
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D016465:Bone Marrow Purging / Q000379:methods*; D002648:Child; D003520:Cyclophosphamide / Q000031:analogs & derivatives; D004341:Drug Evaluation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000601:surgery; D008297:Male; D008775:Methylprednisolone; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000601:surgery; D014182:Transplantation, Autologous; D014750:Vincristine
chemical_list: D014750:Vincristine; D003520:Cyclophosphamide; C011272:perfosfamide; D008775:Methylprednisolone