IDA-FLAG (idarubicin, fludarabine, high dosage cytarabine and G-CSF)--an effective therapy regimen in treatment of recurrent acute myelocytic leukemia in children and adolescents. Initial results of a pilot study

Abstract

Intensive chemotherapy has improved the prognosis of patients with AML. The success rate of relapse treatment correlates with the length of first remission. Thus early relapses and primarily refractory diseases have a grave prognosis. New chemotherapeutic regimens could be useful for those patients. Patients treated for newly diagnosed or relapsed AML with polychemotherapy regimen of the AML-BFM-studies containing induction, consolidation and high-dose cytarabine combined with mitoxantrone (HAM) and relapsed within 2 up to 31 months after the first CR entered a pilot trial, the so called IDA-FLAG regimen. This regimen includes G-CSF (day 0 up to ANC > 1000/microliter, 400 micrograms/m2.d), fludarabine (day 1-4, 30 mg/m2.d), high-dose cytarabine (day 1-4, 2000 mg/m2.d) and idarubicin (day 2-4, 12 mg/m2.d). 10 patients aged 1,8 to 28,1 years (mean = 9,6 years) having the first (n = 8) or second relapse (n = 1) of AML or an acute blastcrisis of myelodysplastic syndrome (n = 1) (FAB classification: M1/M2 = 3, M4/M5 = 5, M7 = 1, CMML = 1) received 14 courses. Overall, 7 patients achieved CR with a mean duration of 8,9 months (1-22 months), one patient showed a partial remission and two were nonresponders. 4 patients are in continuous CR for 7,5 to 22 months (mean = 13,2 months). 3 patients got a bone marrow transplantation (allogenic = 2, autologous = 1) in CR following this treatment. Toxicity was considerable, mainly bone marrow aplasia with leucopenia < 1000/microliter for 15 to 40 days (mean = 26,1 days), neutropenia < 500/microliter for 14 to 39 days (mean = 26,0 days) and thrombocytopenia < 30,000/microliter for 14 to 90 days (mean = 36,5 days). Further important side effects were fever, mucositis and pneumonia. One patient died from an fulminant aspergillus sepsis during long-term neutropenia. The sequential administration of G-CSF, fludarabine, cytarabine and idarubicin is effective in treatment of relapsed AML in childhood and an advisable option prior to allogenic or autologous bone marrow transplantation. With regard to the unfavorable prognosis of relapsed or refractory AML the toxicity of this regimen seems acceptable.