Autologous bone marrow transplantation for acute leukemia using transplant chemopurified with metabolite of oxazaphosphorines (ASTA Z 7557, INN mafosfamide). First clinical results.
The contamination of autologous marrow with clonogenic tumor cells has been the main argument against ABMT in acute leukemia. In a preclinical study we evaluated an active cyclophosphamide derivative named "ASTA Z 7557". We observed that the toxic effect of this drug on CFU-GM growth was dependent on nucleated cell concentration as well as on red blood cell contamination. The potency of the drug was in close relationship with the incubation temperature. The growth of leukemic CFU was inhibited with an ASTA Z dose higher than 30 micrograms/ml. In our system, beyond 40 micrograms/ml more than 95% of committed stem cells are destroyed. Fifteen patients had autotransplant because of AML for 10 patients and because of ALL for 5 patients (4 patients were grafted in relapse and 11 patients in remission). We demonstrated that the marrow take was possible although the inoculum is CFU-GM depleted. Five of the 10 AML patients are alive and remain disease-free at 45+, 65+, 190+, 345+ and 570+ days from ABMT without any maintenance treatment. Four of the 5 ALL patients are alive, three of them in complete remission (40+, 110+, 250+ days). The number of patients reported in this clinical study was relatively small and more cases should be evaluated to be conclusive. Nevertheless the feasibility of chemopurified ABMT was demonstrated.
D000328:Adult; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D004341:Drug Evaluation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007945:Leukemia, Lymphoid / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects*; D014182:Transplantation, Autologous
C037933:Asta Z 7557; D003520:Cyclophosphamide