Fludarabine and cytarabine in patients with acute myeloid leukemia refractory to two different courses of front-line chemotherapy.

The most effective regimen for acute myeloid leukemia (AML) patients who do not achieve complete remission (CR) after two different courses of front-line chemotherapy has not been established. We therefore evaluated the efficacy, toxicity, and prognostic factors for achieving CR following treatment with fludarabine and cytarabine in 25 newly diagnosed AML patients who did not respond to initial therapy with idarubicin and cytarabine followed by mitoxantrone and etoposide. CR was achieved in 32% of patients; in 55% of patients with intermediate-risk karyotype and in 14% with unfavorable-risk. Eight percent died of infectious complications. Median duration of overall survival was 6.6 months (95% CI 3.4 months to ∞); 3.4 months (95% CI 0.8-8.6 months) for patients with an unfavorable-risk karyotype and 18.1 months (95% CI 5.0 months to ∞) with an intermediate-risk karyotype (p=0.02). Our data suggest that poor-risk karyotype patients are unlikely to benefit from third course treatment with fludarabine-cytarabine, and that this regimen merits further investigation in AML patients with good or intermediate-risk karyotype that have persistent leukemia after two courses of front-line chemotherapy.