FLAG-IDA诱导化疗方案中不同剂量阿糖胞苷治疗儿童急性髓系白血病疗效比较

doi:10.12372/jcp.2024.23e0900

摘要/Abstract

摘要：

目的分析儿童急性髓系白血病（AML）在FLAG-IDA诱导化疗方案中接受不同剂量阿糖胞苷的疗效及安全性。方法回顾性分析2015年1月至2022年10月收治的初诊AML患儿的临床资料，依照FLAG-IDA诱导化疗方案中阿糖胞苷使用剂量分为标准剂量和高剂量两组，比较诱导化疗后两组间疗效及毒副反应情况。结果纳入121例AML患儿，男71例、女50例，初诊中位年龄6.7（2.6~10.9）岁。标准剂量组30例，高剂量组91例。与标准剂量组比较，高剂量组诱导化疗的完全缓解率较低，中性粒细胞减少持续时间较短，化疗后天冬氨酸氨基转移酶与丙氨酸氨基转移酶水平较高，差异有统计学意义（P<0.05）。两组间毒副反应差异无统计学意义（P>0.05）。中位随访时间为37.0（12.0~46.0）月。标准剂量组的3年总体生存率和无事件生存率分别为（91.1±6.0）%、（79.5±8.3）%，高剂量组的3年总体生存率和无事件生存率分别为（64.5±11.5）%、（57.5±10.7）%，两组间3年总体生存率和无事件生存率差异均无统计学意义（P>0.05）。结论在诱导化疗中选择标准剂量的阿糖胞苷可能获得更优的疗效，发生肝功能损害的程度相对较低。

关键词: 急性髓系白血病, 阿糖胞苷, 疗效, 儿童

Abstract:

Objective To explore the efficacy and safety of different doses of cytarabine (Ara-C) in FLAG-IDA regimen as induction therapy in children with acute myeloid leukemia (AML). Methods 121 children who newly diagnosed AML from January 2015 to October 2022 were enrolled in this study. Participants were divided into two groups according to the dose of cytarabine used in the FLAG-IDA induction chemotherapy regimen: the standard-dose (SD) group and the high-dose (HD) group. Therapeutic efficacy and toxicity and side effects of the two groups after the induction chemotherapy were compared. Result A total of 121 children with AML were included, 71 males and 50 females, with a median age at first diagnosis of 6.7 (2.6~10.9) years. There were 30 cases in the SD group and 91 cases in the HD group. Compared with the SD group, the CR rate of induction chemotherapy in the HD group was lower, the duration of neutropenia was shorter, and the levels of AST and ALT after chemotherapy were higher, and the difference was statistically significant (P<0.05). There was no statistically significant difference in toxic and side effects between the two groups (P>0.05). The median follow-up time was 37.0 (12.0~46.0) months. The 3-year OS and EFS of the SD group were (91.1±6.0) % and (79.5±8.3) % respectively, and the 3-year OS and EFS of the HD group were (64.5±11.5) %and (57.5±10.7) % respectively. There was no statistically significant difference in 3-year OS and EFS between the two groups (P>0.05). Conclusion Standard-dose cytarabine can obtain better efficacy and less side effects in induction chemotherapy.

Key words: acute myeloid leukemia, cytarabine, efficacy, child

李怡蓉, 李惠萍, 高靖瑜, 肖玉华, 陈小敏, 卢艳玲, 赵娜娜, 冯晓勤. FLAG-IDA诱导化疗方案中不同剂量阿糖胞苷治疗儿童急性髓系白血病疗效比较[J]. 临床儿科杂志, 2024, 42(8): 673-677.

LI Yirong, LI Huiping, GAO Jingyu, XIAO Yuhua, CHEN Xiaomin, LU Yanling, ZHAO Nana, FENG Xiaoqin. Comparison of different doses of cytarabine for induction chemotherapy in children with acute myeloid leukemia in FLAG-IDA regimen[J]. Journal of Clinical Pediatrics, 2024, 42(8): 673-677.

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项目	标准剂量组(n=30)	高剂量组(n=91)	统计量	P
初诊年龄[M(P₂₅~P₇₅)]/岁	9.1(2.6~10.9)	6.2(2.6~11.1)	Z=0.97	0.336
起病WBC≥50×10⁹·L^-1[n(%)]	10(33.3)	19(20.9)	χ²=1.92	0.217
男性[n(%)]	17(56.7)	54(59.3)	χ²=0.07	0.833
髓外浸润[n(%)]	3(10.0)	10(11.0)	χ²=0.02	1.000
ELN风险分层[n(%)]			χ²=2.71	0.259
预后良好	3(10.0)	17(18.7)
预后中等	16(53.3)	34(37.4)
预后不良	11(36.7)	40(44.0)
染色体[n(%)]			χ²=1.08	0.582
正常核型	11(36.7)	42(46.2)
预后良好核型	9(30.0)	20(22.0)
其他核型	10(33.3)	29(31.8)
化疗前AST[M(P₂₅~P₇₅)]/U·L^-1	21(15.8~32.0)	21.0(16.0~31.0)	Z=0.25	0.805
化疗前ALT[M(P₂₅~P₇₅)]/U·L^-1	13(9.0~27.3)	12.0(9.0~21.0)	Z=0.51	0.610

项目	标准剂量组(n=30)	高剂量组(n=91)	统计量	P
诱导缓解为CR[n(%)]	29(96.7)	74(81.1)	－	0.042¹⁾
MRD[n(%)]			－	0.057¹⁾
<0.1 %	10(33.3)	50(55.6)
≥0.1 %	20(66.7)	41(44.4)
ANC减少持续时间( x±s)/d	32.7±7.3	28.2±7.7	t=2.79	0.006
PLT减少持续时间[M(P₂₅~P₇₅)]/d	21.0(17.0~24.0)	20.0(17.0~24.0)	Z=0.64	0.529
HB减少持续时间( x±s)/d	35.6±13.3	31.2±13.9	t=1.52	0.130
毒副反应[n(%)]
药物热	16(53.3)	32(35.2)	χ²=3.11	0.078
药物疹	3(10.0)	2(2.2)	χ²=1.78	0.183
严重感染	4(13.3)	19(20.9)	χ²=0.83	0.361
化疗后AST[M(P₂₅~P₇₅)]/U·L^-1	23.6(16.2~31.0)	31.0(19.5~38.4)	Z=2.00	0.045
化疗后ALT[M(P₂₅~P₇₅)]/U·L^-1	19.5(12.3~30.9)	25.8(15.4~48.5)	Z=2.25	0.024