Toxicity of ASTA Z 7557 (INN mafosfamide) to normal- and leukemic stem cells: Implications for autologous bone marrow transplantation |
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Authors: | Anton Hagenbeek Anton C M Martens |
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Institution: | (1) Radiobiological Institute TNO, Rijswijk, The Netherlands;(2) Dept. of Hematology, Dr. Daniël den Hoed Cancer Center, Rotterdam, The Netherlands;(3) Radiobiological Institute TNO, P.O. Box 5815, 2280 Rijswijk, HV, The Netherlands |
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Abstract: | Summary The activity of the in vitro active cyclophosphamide metabolite ASTA Z 7557 against pluripotent hemo-poietic stem cells (CFU-S), in vitro myeloid precursor cells (CFU-C) and clonogenic leukemic cells (LCFU-S) was evaluated in a rat model for human acute myelocytic leukemia (BNML). LCFU-S were most sensitive (D0 = 10.9 × 10-6 M), followed by CFU-C (D0 = 16.4 × 10-6 M), while CFU-S were least sensitive (D0 = 22.1 × 10-6 M). Per cell population there were considerable variations in response when identical drug concentrations were tested in different experiments under the same standardized conditions.Furthermore, the concentration of leukemic cells in a normal marrow cell suspension appeared to correlate with the cytotoxic action of the drug against leukemia. A decreased cytotoxicity was already observed in mixtures containing 1 leukemic cell per 10 normal marrow cells.The implications of these findings in the BNML model for human autologous bone marrow transplantation are discussed. |
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Keywords: | in vitro chemotherapy ASTA Z 7557 BN rat acute myelocytic leukemia (BNML) hemopoietic stem cells clonogenic leukemic cells autologous bone marrow transplantation |
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