High-dose cytarabine, idarubicin, and granulocyte colony-stimulating factor remission induction therapy for previously untreated de novo and secondary adult acute myeloid leukemia.

This report describes the preliminary results of the remission induction phase of a protocol for previously untreated de novo and secondary acute myeloid leukemia (AML) designed to deliver very intensive therapy over a brief period of time using hematopoietic growth factor support. Remission induction therapy consisted of cytarabine 3 g/m2 (1.5 g/m2 for age > 50 years) intravenously over 1 hour every 12 hours for 12 doses and idarubicin 12 mg/m2 over 30 minutes on days 2, 3, and 4 of cytarabine, followed by 10 micrograms/kg granulocyte colony-stimulating factor subcutaneously daily until the absolute neutrophil count increased to > or = 5.0 x 10(9)/L on 2 consecutive days. Twenty-seven patients received all the planned doses of chemotherapy. The complete remission (CR) rate to a single course of therapy was 65% in 20 patients with de novo AML (median age, 60.5 years; age range, 26 to 78 years); for those aged less than 60 and > or = 60 years, the CR rates were 90% and 40%, respectively. In contrast, only two of 10 patients with secondary AML (median age, 68 years; age range, 35 to 77 years) achieved a CR. The median time from initiation of chemotherapy to recovery of 0.5 x 10(9)/L neutrophils in de novo AML patients achieving CR was 20 days (range, 18 to 23 days). Median times to last platelet transfusion and to 100 x 10(9)/L platelet count were 23 days (range, 18 to 41 days) and 28 days (range, 24 to 97 days), respectively. The major nonhematologic toxicity was transient hyperbilirubinemia, which was observed in 64% of patients. Reversible cerebellar toxicity was seen in three patients. Thus, idarubicin at full dose (12 mg/m2 x 3 days) may be safely administered with high-dose cytarabine, even in elderly patients. The use of granulocyte colony-stimulating factor is associated with rapid neutrophil recovery without obvious toxicity. The CR rate for de novo AML patients treated with a single course of high-dose cytarabine, idarubicin, and granulocyte colony-stimulating factor is at least comparable to CR rates achieved with standard-dose cytarabine and anthracycline regimens. The response of secondary AML patients remains inferior.