FLAG方案治疗小儿复发难治性急性白血病临床研究

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

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)×5+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AML CR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。

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 5 μg/ （ 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, re- spectively. The median duration of ANC 〉0. 5 × 109/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-t^ansplant pa- tients, 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; g 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, es- pecially for patients with relapsed AML and treatment as a first line regimen.