FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of 'poor risk' acute myeloid leukemias.

Twenty-eight patients with poor prognosis acute myeloid leukemia (AML) received therapy with two courses of fludarabine 30 mg/m2/day + ara-C 2 g/m2/day (days 1-5) and G-CSF 5 mg/kg/day (FLAG) (from day 0 to polymorphonuclear recovery). Eighteen patients were considered 'refractory' (eight primarily resistant, five relapsing within 6 months of initial remission, or at a second relapse; five relapsing after an autologous bone marrow transplantation procedure. Ten cases were defined 'secondary' AML (diagnosis of AML made after a preexisting diagnosis of: myelodysplastic syndrome: five cases; myelodysplastic syndrome after therapy for breast cancer: one case; previously untreated, and concomitant, non-Hodgkin's lymphoma: two cases; Hodgkin's disease treated with chemoradiotherapy: one case). Overall, 15 patients (58%) achieved a complete remission (CR). Two patients died of infection during induction, and 11 had resistant disease. Analyzing the data in relation to selected host and disease characteristics, the response varied widely. The highest CR rates (89%) were obtained in secondary AML; in particular, two cases of 'second-primary' (concomitant with low-grade non-Hodgkin's lymphoma) AML obtained CR for both diseases. Refractory AML differed widely for response: high CR rate (75%), although with short mean CR duration for primary resistance AML, and very poor response (11% CR) for relapsed (early, second, after ABMT) cases. Interestingly, a slow kinetic of leukemic growth in vivo before FLAG administration was significantly related to the response and outcome (p = 0.0002). Hematological and nonhematological toxicities were acceptable. In conclusion, the FLAG regimen has significant antileukemic activity and acceptable toxicity especially in secondary AML, both with and without coexisting lymphoid malignancy.