No preferential sensitivity of clonogenic AML cells to ASTA-Z-7557.

Abstract

ASTA-Z-7557, an in vitro active metabolite of cyclophosphamide, has recently been introduced to purge autologous bone marrow grafts of patients with AML. The rationale of this approach assumes a relatively higher sensitivity of leukemic cells to the drug as compared to that of normal marrow precursors. We have investigated in direct comparison the sensitivity to ASTA-Z-7557 of normal bone marrow progenitors (GM-CFC and BFU-E) and clonogenic leukemic cells (L-CFC). Normal bone marrow cells and purified leukemic blast cells were exposed to varying concentrations of the drug. Dose-response relationships did not indicate a selective cytotoxic susceptibility of L-CFC to ASTA-Z-7557. The recovery of bone marrow precursors following exposure to ASTA-Z-7557 depended on the cell concentration during exposure and was higher for 2 X 10(7) cells/ml than for 1 X 10(6)/ml. To mimic minimal residual leukemia cell mixtures of 95% irradiated normal bone marrow cells with 5% leukemic blast cells were exposed to ASTA-Z-7557. In this mixture killing of L-CFC was largely decreased. These data suggest that in vitro incubation of autologous bone marrow grafts of patients with minimal residual leukemia with ASTA-Z-7557 might not offer a therapeutic advantage.

• Authors: H C Kluin-Nelemans, A C Martens, B Löwenberg, A Hagenbeek
• Journal: Leukemia research (Leuk Res) Vol. 8 Issue 4 Pg. 723-8 ( 1984) ISSN: 0145-2126 [Print] England
• PMID: 6590937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Asta Z 7557
• Cyclophosphamide

Topics

• Cell Survival (drug effects)
• Cells, Cultured
• Cyclophosphamide (analogs & derivatives, pharmacology, therapeutic use)
• Hematopoietic Stem Cells (drug effects)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, pathology)