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 remains a challenge. The morbidity of further chemotherapy is considerable, as most patients have already been exposed to intensive multiagent chemotherapy. The FLAG (fludarabine, high-dose cytarabine, and G-CSF) regimen is as intensive but less cardiotoxic because of the avoidance of anthracyclines.


METHODS
Nineteen children were treated in two U.K. centers with the FLAG regimen for relapsed and refractory acute myeloid leukemia (AML) and acute 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 in 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 obtained in 4, and 2 patients were considered nonresponders. There were seven patients alive at 12 months (mean) posttherapy; one of these is awaiting bone marrow transplantation (BMT). All patients experienced grade 4 hematological toxicity; no patient died of infection. Thirteen patients received BMT as consolidation (seven unrelated donor; six sibling allografts). Six of these have died, four due to pneumonitis.


CONCLUSIONS
FLAG can be regarded as an effective protocol for inducing remission in a group of heavily pretreated children. Its toxicity is acceptable due to the avoidance of anthracyclines.
McCarthy
A J
AJ
Royal Hospital for Sick Children, Bristol, United Kingdom. amcc@nildram.co.uk
Pitcher
L A
LA
Hann
I M
IM
Oakhill
A
A
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000628:therapy; D012008:Recurrence; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine