Treatment of core‐binding‐factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony‐stimulating factor results in improved event‐free survival

Abstract BACKGROUND. Acute myelogenous leukemia (AML) associated with core‐binding‐factor (CBF) abnormalities is the type of leukemia most responsive to cytarabine (ara‐C) therapy and is of relative favorable prognosis. In vitro and ex vivo observations suggest that increases in intracellular ara‐C levels influenced by administration of fludarabine and granulocyte colony‐stimulating factor (GCSF) increase the effect of ara‐C, prompting us to clinically evaluate the efficacy of such combinations. METHODS. We analyzed the event‐free survival of patients with newly diagnosed CBF AML treated with fludarabine and ara‐C (FA) (N = 45) or with FA and GCSF (FLAG) (N = 22) and compared results to patients treated with regimens consisting of idarubicin and ara‐C with or without GCSF (IA/IAG) (N = 47). RESULTS. After accounting for prognostic covariates other than treatment (including year in which treatment was administered), FA, and in particular FLAG, were associated with longer event‐free survival than IA/IAG. CONCLUSIONS. Thus, our data lends clinical credence to the observed modulation of ara‐C by fludarabine and GCSF. Cancer 2008. © 2008 American Cancer Society.