Induction failures in childhood acute nonlymphocytic leukemia: etoposide/5-azacytidine for cases refractory to daunorubicin/cytarabine.

Treatment with a combination of daunorubicin (45 mg/m2 IV, days 1-3) and cytarabine (100 mg/m2 continuous IV infusion, days 4-10) failed to induce complete remission in 31 of 87 children (36%) with acute nonlymphocytic leukemia (ANLL). Six patients with monocytic or promyelocytic leukemia died before day 14 of therapy from complications of hyperleukocytosis and coagulopathy; an additional 10 failed because of fatal infections associated with drug-induced marrow hypoplasia, and the remaining 15 had residual leukemia despite receiving two courses of daunorubicin and cytarabine. Alternative therapy with etoposide (250 mg/m2, IV, days 1-3, 7-9) and 5-azacytidine (300 mg/m2 IV, days 4, 5, 9, 10) induced complete remission in nine (60%) of the 15 patients with resistant leukemia. Among the six children who failed to respond to either regimen, three had cytochemical and immunophenotypic features indicative of acute mixed-lineage leukemia, and one had monosomy 7 syndrome. Our findings suggest that the addition of etoposide and 5-azacytidine to a basic daunorubicin-cytarabine regimen would increase remission induction rates in childhood ANLL. Careful determination of pretreatment characteristics, including blast cell immunophenotype and cytogenetic properties, are needed to identify unusual cases of ANLL that may require selective therapy.