Suitability of a new stable acetal analogue of aldoifosphamide for purging leukemic cells from human bone marrow |
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Authors: | B S Andersson Y Q Wang K B McCredie D Farquhar |
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Affiliation: | Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston 77030. |
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Abstract: | The in vitro cytotoxic properties of acetaldoifosphamide, a new chemically stable bis-acetate analogue of aldoifosphamide that requires enzymatic activation by cellular carboxylate esterases, has been compared with that of 4-hydroperoxycyclophosphamide (4-HC). On a molar basis, acetaldoifosphamide was 8-10 times more potent than 4-HC against two different human leukemic myeloid cell lines, but only twice as potent as 4-HC against normal bone marrow granulocyte-macrophage colony-forming cells (GM-CFC). Acetaldoifosphamide retained its activity against leukemic cell lines that were highly resistant to the antileukemic drugs doxorubicin and m-AMSA. GM-CFC doubling times after exposure of bone marrow to high concentrations of acetaldoifosphamide in suspension cultures were 6-12 hours. Similar doubling times were obtained after incubation of marrow with 4-HC. Acetaldoifosphamide has a sparing effect on hematopoietic stem cells that is similar to that found for 4-HC; however, it is considerably more potent than 4-HC. Acetaldoifosphamide is different from 4-HC in its chemical stability and its unique requirement for carboxylate esterase activation. We conclude that acetaldoifosphamide may have advantages over 4-HC for in vitro purging of leukemic cells from human bone marrow. |
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