Treatment of Childhood Acute Nonlymphocytic Leukemia with Individually Scheduled High Doses of Cytarabine: Preliminary Results of Study ANLL-82 of the Dutch Childhood Leukemia Study Group (DCLSG)
Experimental studies in animals have shown that high doses of cytosine arabinoside (HDARA-C) induce synchronization and possible recruitment of leukemic cells. Administration of a second HDARA-C injection at the moment of maximal accumulation of cells in S-phase resulted in the most effective reduction (one log) of leukemic cells . In a pilot study (ANLL-80) of 24 children with acute nonlymphocytic leukemia (ANLL), 12 injections of HDARA-C were administered at 24-h intervals, followed by two injections of adriamycin, which resulted in a remission rate of 71%. Without further treatment, however, early relapses occurred in the majority of these children. Cell kinetic studies in children with relapsed ANLL have shown a considerable range in the proliferative status of their disease, measured by flow cytometry. The percentage of cells in S-phase in the bone marrow (BM) at the time of relapse varied between 3.5% and 14%. An inverse relationship between the percentage of cells in S-phase at relapse and the time interval up to maximal accumulation of cells in S-phase after one injection of HDARA-C (1 g/m2) was established. The correlation between these two parameters was laid down in a “calibration curve” . The current protocol, ANLL-82, with an individually scheduled induction course consisting of 12 injections of HDARA-C and one injection of adriamycin, is based on these findings. In children in remission this was followed by allogeneic bone marrow transplantation (BMT) or maintenance treatment according to the VAPA-10 protocol .
KeywordsToxicity Leukemia Oncol Cytosine Adriamycin
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