Cytosine arabinoside in the treatment of T-cell acute lymphoblastic leukemia

Abstract

The place of cytosine arabinoside (araC) in the treatment of T-cell acute lymphoblastic leukemia was studied by measuring nucleoside transport sites and the conversion of araC to its triphosphate (araCTP) in lymphoblasts from the peripheral blood of two patients, who were then treated with araC. Equilibrium binding of 3H-nitrobenzylmercaptopurine riboside (3H-NBMPR), a specific ligand of the nucleoside transporter, gave 16,510 to 29,400 sites/cell for T-lymphoblasts on presentation or early in relapse compared with 2730 +/- 1570 sites/cell for non-T-lymphoblasts. Accumulation of araCTP from 1 microM araC was four times greater in T-cell than non-T-cell lymphoblasts. One patient was treated with araC (100 mg/m2 daily x 7 days, continuous intravenously) at the time of her first leukemic relapse and complete remission was achieved with this single agent. When this patient relapsed and developed advanced disease the T lymphoblasts showed a 75% reduction in their ability to accumulate araCTP which paralleled a reduction in 3H-NBMPR binding. The second patient achieved complete remission with araC given in low dose (15 mg twice daily by subcutaneous injection) for 21 days at the time of a localised relapse in the mediastinum and pleura. These studies suggest that araC may have a place in the therapy of early stage T-lymphoblastic disease.