CYTOKINETICALLY BASED INDUCTION CHEMOTHERAPY AND SPLENECTOMY FOR CHILDHOOD ACUTE NONLYMPHOCYTIC LEUKEMIA

Abstract

A 4-drug regimen, based on cell kinetic principles, induced complete remissions in 68 of 95 children (72%) with acute nonlymphocytic leukemia (ANLL). Patients entered remission after 2-5 weekly cycles of vincristine-daunorubicin (day 1) followed by sequential cytosine arabinoside and 6-azauridine (days 4-7). With continuation therapy of monthly vincristine-doxorubicin-cyclophosphamide, weekly cytosine arabinoside, and daily 6-mercaptopurine, the median duration of complete remission was 10 mo. and the median survial time, 21 mo. Portal triaditis, evident in 11 of 23 patients with liver biopsies, was associated with long remissions. A larger spleen size (> 5 cm) and a higher myeloblast labeling index (> 10%) at diagnosis were clearly related to shorter durations of remission. Splenectomy within 1 mo. of remission had no statistically significant effect on the frequency of relapse or length of remission. Patients without CNS leukemia at diagnosis, all treated prophylactically with intrathecal methotrexate, had a low frequency of initial CNS relapse (3/56, 5%). The 2-yr disease-free survival rate is 29% (20 of 68 patients attaining complete remission). Fifteen patients have completed 2.5 yr of therapy, and each remains in continuous complete remission, off treatment, for 1+ to 36+ mo. This induction chemotherapy was as effective as more intensive regimens, with the advantage of less toxicity and shorter periods of hospitalization.