Quarello Paola, Berger Massimo, Rivetti Elisa, Galletto Chiara, Masetti Riccardo, Manicone Rosaria, Barisone Elena, Pession Andrea, Fagioli Franca
Regina Margherita Children's Hospital, Turin, Italy.
J Pediatr Hematol Oncol. 2012 Apr;34(3):208-16. doi: 10.1097/MPH.0b013e3182427593.
Despite the success in treating the majority of children with newly diagnosed acute leukemia, children with relapsed or refractory disease are an exceptionally difficult group of patients to cure. We assessed the combination of fludarabine with cytarabine and granulocyte colony-stimulating factor (FLAG) and nonpegylated liposomal doxorubicin (Myocet) in children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) refractory to first-line therapy or who had relapsed after risk-tailored chemotherapy. We treated 35 patients with FLAG-Myocet. The median age at treatment was 9 years and 7 months (range, 1 to 18 y). The 94% of ALL patients (16/17) and the 61% AML patients (11/18) achieved complete remission after FLAG-Myocet. A partial response was observed in the 17% of AML patients (3/18). Twenty-eight of 35 (80%) patients received hematopoetic stem cell transplantation in remission induced by FLAG-Myocet regimen. The ALL and AML overall survival at 3 years after FLAG-Myocet is 33% and 38%, respectively. The probability of ALL and AML event-free survival at 3 years after FLAG-Myocet is 33% and 40%, respectively. The probability of ALL and AML disease-free survival at 3 years after hematopoietic stem cell transplantation is 19% and 58%, respectively. Nonhematological toxicity was remarkably low, while almost all patients showed severe hematological toxicity. FLAG-Myocet is an efficient and a well-tolerated regimen that allows nearly all patients to undergo hematopoetic stem cell transplantation. FLAG-Myocet proved to be safe in terms of acute cardiac toxicity although particular care must be taken to reduce infectious complications due to severe myelosuppression. The promising results shown in our study need to be confirmed by larger and possibly randomized trials.
尽管在治疗大多数新诊断的急性白血病儿童方面取得了成功，但复发或难治性疾病的儿童是一组极难治愈的患者。我们评估了氟达拉滨与阿糖胞苷和粒细胞集落刺激因子（FLAG）以及非聚乙二醇化脂质体阿霉素（Myocet）联合使用，用于一线治疗难治或在风险调整化疗后复发的急性淋巴细胞白血病（ALL）或急性髓性白血病（AML）儿童。我们用FLAG-Myocet治疗了35例患者。治疗时的中位年龄为9岁7个月（范围1至18岁）。94%的ALL患者（16/17）和61%的AML患者（11/18）在接受FLAG-Myocet治疗后实现完全缓解。17%的AML患者（3/18）观察到部分缓解。35例患者中有28例（80%）在FLAG-Myocet方案诱导缓解后接受了造血干细胞移植。FLAG-Myocet治疗后3年ALL和AML的总生存率分别为33%和38%。FLAG-Myocet治疗后3年ALL和AML无事件生存率分别为33%和40%。造血干细胞移植后3年ALL和AML无病生存率分别为19%和58%。非血液学毒性非常低，而几乎所有患者都表现出严重的血液学毒性。FLAG-Myocet是一种有效且耐受性良好的方案，几乎允许所有患者接受造血干细胞移植。尽管必须特别注意减少由于严重骨髓抑制引起的感染并发症，但就急性心脏毒性而言，FLAG-Myocet被证明是安全的。我们研究中显示的有前景的结果需要通过更大规模且可能是随机的试验来证实。
