Toxicity of ASTA Z 7557 (INN mafosfamide) to normal- and leukemic stem cells: implications for autologous bone marrow transplantation.

Abstract

The activity of the in vitro active cyclophosphamide metabolite ASTA Z 7557 against pluripotent hemopoietic 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 X 10(-6) M), followed by CFU-C (D0 = 16.4 X 10(-6) M), while CFU-S were least sensitive (D0 = 22.1 X 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.

• Authors: A Hagenbeek, A C Martens
• Journal: Investigational new drugs (Invest New Drugs) Vol. 2 Issue 2 Pg. 237-43 ( 1984) ISSN: 0167-6997 [Print] United States
• PMID: 6381383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Asta Z 7557
• Cyclophosphamide

Topics

• Animals
• Bone Marrow Transplantation
• Cell Survival (drug effects)
• Colony-Forming Units Assay
• Cyclophosphamide (analogs & derivatives, pharmacology)
• Hematopoietic Stem Cells (drug effects)
• Leukemia, Experimental (therapy)
• Mice
• Neoplastic Stem Cells (drug effects)
• Rats
• Rats, Inbred BN
• Stem Cells (drug effects)
• Transplantation, Autologous
• Tumor Stem Cell Assay