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

Abstract

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. Procedure 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. Med. Pediatr. Oncol. 32:411–415, 1999. © 1999 Wiley‐Liss, Inc.

FLAG-liposomal Doxorubicin (Myocet) Regimen for Refractory or Relapsed Acute Leukemia Pediatric Patients

“…13,16,[22][23][24][25] McCarthy and colleagues showed the results of FLAG regimen in a heterogeneous group of 19 children heavily pretreated with intensive multiagent chemotherapy because of multiple relapses or primary resistant acute leukemias. Twelve patients had a primary diagnosis of AML, 4 patients had ALL and 3 patients had biphenotypic leukemia.…”

“…Although all patients suffered prolonged neutropenia, only 1 episode of severe sepsis was experienced. 22 The addition of anthracyclines seems to improve the antileukemic activity of FLAG even though the cumulative toxicity and mainly drug-induced cardiotoxicity limit their administration especially in heavily pretreated patients.…”

Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group

“…Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Several studies demonstrated that the combination of FAMP and cytarabine (FAMP/AC) [23][24][25][26] or FAMP/AC plus IDA were efficacious and tolerable in both adults and children with refractory or recurrent AML. [27][28][29][30] After induction therapy, CCG-2961 compared FAMP/AC/IDA as described by Avramis et al to a second course of hybrid 5-drug IdaDCTER therapy.…”

Phase I and pharmacokinetic study of 3′-C-ethynylcytidine (TAS-106), an inhibitor of RNA polymerase I, II and III,in patients with advanced solid malignancies

“…For example, cytarabine and fludarabine remain amongst the most active, broad-spectrum antileukemic agents available [24][25][26], whereas gemcita- bine has demonstrated clinically relevant antitumor activity in patients with non-small cell lung, pancreatic, bladder, ovarian and breast cancers [11,12,[27][28][29][30]. More recently, decitabine and clofarabine have received regulatory approval in the United States and elsewhere for the treatment of myelodysplastic syndromes and pediatric leukemias, respectively [31], further demonstrating that the development of novel nucleoside analogs may produce incremental clinical benefit.…”