FLAG (fludarabine, high-dose cytarabine, and G-CSF) for refractory and high-risk relapsed acute leukemia in children

Background. The treatment of relapsed and refractory leukemia in children r emains a challenge. The morbidity of further chemotherapy is considerable, as most patients have already been exposed to intensive multiagent chemothe rapy. The FLAG (fludarabine, high-dose cytarabine, and G-CSF) regimen is as intensive but less cardiotoxic because of the avoidance of anthracyclines. Procedure. Nineteen children were treated in two U.K. centers with the FLA G regimen for relapsed and refractory acute myeloid leukemia (AML) and acut e lymphoblastic leukemia (ALL). There were 13 males and 6 females, with an age range of 1.9 to 14.2 years. AML was the diagnosis in 12 children, ALL i n 4, biphenotypic leukemia in 3. Eight patients had refractory disease, 11 were in relapse (5 in first relapse, 4 in second, and 2 in third). Results. Complete remission was obtained in 13 patients, partial remission was obta ined in 4, and 2 patients were considered nonresponders. There were seven p atients alive at 12 months (mean) posttherapy; one of these is awaiting bon e marrow transplantation (BMT). All patients experienced grade 4 hematologi cal toxicity; no patient died of infection. Thirteen patients received BMI as consolidation (seven unrelated donor; six sibling allografts). Six of th ese have died, four due to pneumonitis. Conclusions. FLAG can be regarded a s an effective protocol for inducing remission in a group of heavily pretre ated children. Its toxicity is acceptable due to the avoidance of anthracyc lines. (C) 1999 Wiley-Liss, Inc.