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)

Abstract

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 [1]. 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” [2]. 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 [3].

This report is also on behalf of G. E. van Zanen, J. de Koning, J. A. Rammeloo, W.A. Kamps, E. F. van Leeuwen, F. A. E. Nabben, E. J. M. Sjamsoedin-Visser, G. A. M. de Vaan, F. C. de Waal, R. S. Weening, and E. R. van Wering.