Abstract
The arabinoside cytosine (Ara-C) dose-response relationship was investigated in a slow-growing rat leukemia (BNML) which is a realistic model for human acute myelocytic leukemia (AML). For both the tumor load reduction determined as leukemic colony-forming units spleen (LCFU-s) and the normal stem cell toxicity determined as colony forming units spleen (CFU-s), a plateau curve was observed. Maximum LCFU-s reduction was observed after high-dose Ara-C (200 mg/kg), while the greatest CFU-s reduction occurred following a ten fold lower dose. For the high Ara-C dose, several methods of administration were compared: rapid intravenous (IV), intramuscular, subcutaneous, intraperitoneal, and continuous infusion. The most effective tumor load reduction was obtained by rapid IV interval treatment. In addition, rapid IV interval administration of Ara-C was less toxic to normal bone marrow stem cells than continuous infusion of the drug. The results of these studies may justify the application of high-dose Ara-C interval treatment in human AML.
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