McCarthy A J, Pitcher L A, Hann I M, Oakhill A
Royal Hospital for Sick Children, Bristol, United Kingdom.
Med Pediatr Oncol. 1999 Jun;32(6):411-5. doi: 10.1002/(sici)1096-911x(199906)32:6<411::aid-mpo3>3.0.co;2-k.
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.
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).
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.
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.
儿童复发难治性白血病的治疗仍然是一项挑战。进一步化疗的发病率相当高，因为大多数患者已经接受过强化多药化疗。FLAG（氟达拉滨、大剂量阿糖胞苷和粒细胞集落刺激因子）方案同样强化，但由于避免使用蒽环类药物，心脏毒性较小。
19名儿童在英国的两个中心接受FLAG方案治疗复发难治性急性髓细胞白血病（AML）和急性淋巴细胞白血病（ALL）。其中男性13名，女性6名，年龄范围为1.9至14.2岁。12名儿童诊断为AML，4名诊断为ALL，3名诊断为双表型白血病。8名患者患有难治性疾病，11名患者复发（5名首次复发，4名第二次复发，2名第三次复发）。
13名患者获得完全缓解，4名患者获得部分缓解，2名患者被认为无反应。治疗后12个月（平均）有7名患者存活；其中1名正在等待骨髓移植（BMT）。所有患者均经历4级血液学毒性；无患者死于感染。13名患者接受BMT作为巩固治疗（7名无关供体；6名同胞异体移植）。其中6名患者死亡，4名死于肺炎。
FLAG可被视为诱导一组经过大量预处理儿童缓解的有效方案。由于避免使用蒽环类药物，其毒性是可以接受的。
