FLAG方案治疗小儿复发难治性急性白血病临床研究

目的探讨FLAG方案（氟达拉滨，阿糖胞苷，粒细胞集落刺激因子）治疗小儿复发难治性急性白血病的疗效。方法采用FLAG方案[氟达拉滨30mg／（m^2·d）X5＋阿糖胞苷2g／（m^2·d）×5d＋粒细胞集落刺激因子5μg/（kg·d）]治疗21例2—13岁的小儿复发难治性急性白血病，其中急性非淋巴细胞性白血病（AML）15例，急性淋巴细胞性白血病（ALL）6例。首次复发（R1）后首选FLAG方案者8例，次选10例，原发难治2例，第三次缓解（CR3）后FLAG巩固治疗1例。结果21例患儿中1例作为缓解后巩固治疗，1例因化疗后感染死亡而无法评估FLAG应用后缓解率；其他19例可评估患儿中9例（47％）获完全缓解（CR），3例（16％）部分缓解（PR），7例（37％）无效（NR），总有效率63％。其中AMLCR率57％，ALL为20％；R1后首选FLAG方案者CR率为57％，次选为20％。应用FLAG后患儿中性粒细胞〉0．5×10^9／L的中位时间为21（12～36）天，血小板〉20×10^9/L的中位时间为19．4（13～30）天。21例患儿中18例合并感染（86％），除1例死亡外其余均得到有效控制，治疗相关死亡率为4．76％。FLAG治疗后7例患儿进行了造血干细胞移植治疗，目前2例无病存活，分别已移植后无病生存14个月和56个月，其他4例死于移植相关并发症，1例死于移植后复发。另外14例非移植患儿中1例因FLAG相关感染死亡，7例因NR而放弃治疗或合并感染死亡，FLAG治疗有效的6例患儿中2例放弃治疗，4例复发死亡。本组患儿FLAG治疗后中位生存时间5个月。结论FLAG方案治疗小儿复发难治性白血病疗效肯定，毒副作用可以耐受；AML选择FLAG的疗效优于ALL；复发后首选FLAG治疗效果好于次选者。

Clinical study of FLAG regimen for children with relapsed or refractory acute leukemia

Objective To evaluate the efficacy of FLAG regimen in children with relapsed or refractory acute leukemia. Methods Totally 21 cases with relapsed or refractory leukemia(15 ALL,6 AML) were enrolled in this study.Fludarabine 30mg/(m~2·d)×5d+cytosine arabinoside 2g/(m~2·d)×5d+granulocyte-colony stimulating factor 5μg/(kg·d)×5d were used as the FLAG regimen.The median age in this group was 7(range 2-13) years old.FLAG was chosed in 8 patients as the first line treatment and in 10 patients as the second-line regimen after leukemia relapse.Another 2 primary refractory and 1 CR3 ALL patients received FLAG also.Results Nineteen of the 21 patients were eligible for assessment.Nine (47%) and 3(16%) patients achieved complete and partial remission with the overall response rate of 63%.57%CR and 20%PR was obtained in AML and ALL and 57%and 20%CR was gotten as first and second line treatment after relapse,respectively. The median duration of ANC>0.5×10~9/L was 21(12-36) days and platelet>20×10~9/L was 19.4(13- 30) days.Eighteen of 21 patients(86%) suffered severe infection during the regimen and all resolved after active antibiotic except 1 died of infection.The treatment-related mortality was 4.76%in this group.After achieving complete remission,7 patients received allogeneic stem cell transplantation,2 patients survived until the post transplant follow-up 14m and 56m; 4patients died of transplant-related complications and 1 died of post-transplant relapse.For the other 14 non-transplant patients, 1 died of infection during the FLAG regimen.Seven no-response cases died of giving up treatment or infection;Among 6 CR or PR patients 2 gave up treatment after remission;4 died of infection after relapse.Median survival was 5months in all cases.Conclusion FLAG seems to be a good choice and well tolerated in children with relapsed or refractory leukemia,especially for patients with relapsed AML and treatment as a first line regimen.