Ex vivo elimination of lymphoblastic leukemia cells from human marrow by mafosfamid.
Studies were performed to evaluate the anti-tumor activity of mafosfamid, a new synthetic derivative of cyclophosphamide. We tested its ability to eliminate lymphoblastic leukemia cells from autologous bone marrow grafts following a 30 min preincubation in a highly sensitive clonogenic assay. Treatment with 50-100 micrograms mafosfamid/ml eliminated more than 4 logs of contaminating clonogenic tumor cells from a 200-fold excess of normal bone marrow. Flow cytometric studies showed differences in cell cycle kinetics between mafosfamid-resistant and mafosfamid-susceptible tumor cell clones. Compared to drug susceptible clonogenic tumor cells, clones that resisted treatment with 100 micrograms mafosfamid/ml exhibited a smaller percentage of cells in S-phase, indicating that mafosfamid is mostly cytotoxic to rapidly cycling tumor cells. The combination of mafosfamid and a target cell selective immunotoxin containing pokeweed anti-viral protein was superior to mafosfamid alone or immunotoxin alone for purging mafosfamid-resistant leukemic cells from human marrow.
D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004351:Drug Resistance; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000473:pathology*; D014410:Tumor Stem Cell Assay
D004273:DNA, Neoplasm; C037933:Asta Z 7557; D003520:Cyclophosphamide