Fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin for relapsed childhood acute myeloid leukemia

BackgroundThe combination of fludarabine (Flu), high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF; FLAG), with anthracyclines has become standard chemotherapy for refractory acute myeloid leukemia (AML) in European children and adults. To clarify the efficacy and the safety of FLAG-idarubicin (IDA) for children prospectively, we planned a multicenter phase II study (AML-R11) by the Japanese Pediatric Leukemia/Lymphoma Study Group. MethodsPatients with AML aged between 2 and 20years old, who had the first bone marrow (BM) relapse or induction failure, were enrolled. The FLAG-IDA regimen consisted of Flu 30mg/m(2) for 5days, Ara-C 2g/m(2) for 5days, G-CSF (lenograstim) 5g/kg for 6days and IDA 10mg/m(2) for 3days. The primary endpoint was remission rate after therapy. ResultsDue to drug supply issues, the trial was suspended after the inclusion of seven eligible patients. There were six cases of early relapse within 1year of the first remission. All seven patients completed the therapy and no early death was observed. Hematological toxicity was common, and one patient developed grade 4 non-hematological toxicity of bacterial meningitis. Although only one patient with late relapse achieved complete remission, minimal residual disease was positive on both flow cytometry and Wilms' tumor 1 mRNA. Two patients were alive in remission following hematopoietic stem cell transplantation, whereas the other five patients died of either the disease or treatment-related causes. ConclusionFLAG-IDA might be tolerable for children with refractory AML although the efficacy should be further investigated.