改良CLAG方案治疗儿童复发/难治急性髓系白血病的疗效和安全性

doi:10.12372/jcp.2024.23e0555

摘要/Abstract

摘要：

目的探讨减低化疗剂量的改良CLAG方案（克拉屈滨、阿糖胞苷、粒细胞集落刺激因子）治疗复发/难治急性髓系白血病（R/R-AML）儿童的疗效及安全性。方法回顾性分析2016年6月至2023年4月接受改良CLAG方案治疗的R/R-AML患儿的临床资料，计算总体反应率（ORR）、不良反应发生率、总生存（OS）率和无事件生存（EFS）率。结果 26例患儿中复发17例，其中1例为睾丸白血病复发，3例为骨髓2次复发，余均为骨髓首次复发，难治9例。所有患儿均完成1疗程改良CLAG方案化疗，1例未评估治疗反应桥接造血干细胞移植，余25例患儿ORR为84.0 %（21/25）。复发患儿的ORR为81.3 %（13/16），难治患儿的ORR为88.9 %（8/9）。细胞遗传学分层为低危的患儿ORR为76.9 %（10/13），中高危患儿ORR为91.7 %（11/12）。所有患儿64个月的OS率和EFS率分别为69.7 %和63.3 %，15例治疗有反应并顺利桥接异基因造血干细胞移植的患儿64个月OS率和EFS率均为92.3 %。最常见的不良反应为骨髓抑制（100 %）和胃肠道反应（100 %），其次为感染（57.7 %）、转氨酶升高（34.6 %）、出血（19.2 %），1例患儿因4级颅内出血放弃，其他不良反应均经对症治疗后好转。结论减低化疗剂量的改良CLAG方案是儿童R/R-AML的一种有效、安全的治疗选择。

关键词: 急性髓系白血病, 复发/难治, 疗效, 安全性, 儿童

Abstract:

Objective To investigate the efficacy and safety of modified CLAG regimen (cladribine + cytarabine + granulocyte colony-stimulating factor) with reduced chemotherapy dose in the treatment of children with relapsed/refractory acute myeloid leukemia (R/R-AML). Methods The clinical data of children with R/R-AML treated with the modified CLAG regimen from June 2016 to April 2023 were retrospectively analyzed, and the overall response rate (ORR), incidence of adverse reactions, overall survival (OS) rate, and event-free survival (EFS) rate were calculated. Results Among all the children, 17 had recurrent AML, of them 1 had testicular leukemia recurrence, 3 had secondary recurrence in the bone marrow, and the rest had first recurrence in the bone marrow. Nine patients had refractory AML. All children completed 1 course of chemotherapy with modified CLAG regimen, and hematopoietic stem cell transplantation (HSCT) was bridged in 1 patient with no assessed response to treatment, with an ORR of 84.0 % (21/25) in the remaining 25 children. The ORR was 81.3 % (13/16) in the relapsed children and 88.9 % (8/9) in the refractory children. The ORR was 76.9 % (10/13) in children with low risk cytogenetic stratification and 91.7 % (11/12) in children with moderate and high risk cytogenetic stratification. The 64-month OS and EFS rates of all patients were 69.7 % and 63.3 %, respectively. The 64-month OS and EFS rates of 15 children who responded to treatment and successfully bridged allogeneic HSCT were 92.3 %. The most common adverse reactions were myelosuppression (100 %) and gastrointestinal reactions (100 %), followed by infection (57.7 %), elevated transaminases (34.6 %), and bleeding (19.2 %), and one child abandoned treatment due to grade 4 intracranial hemorrhage. All other adverse reactions were improved after symptomatic treatment. Conclusions The modified CLAG regimen with reduced chemotherapy dose is an effective and safe treatment option for children with R/R-AML.

Key words: acute myeloid leukemia, relapsed or refractory, efficacy, safety, child

尚倩雯, 张永湛, 陆爱东, 贾月萍, 左英熹, 丁明明, 张乐萍, 曾慧敏. 改良CLAG方案治疗儿童复发/难治急性髓系白血病的疗效和安全性[J]. 临床儿科杂志, 2024, 42(7): 589-594.

SHANG Qianwen, ZHANG Yongzhan, LU Aidong, JIA Yueping, ZUO Yingxi, DING Mingming, ZHANG Leping, ZENG Huimin. The efficacy and safety of modified CLAG regimen for relapsed or refractory acute myeloid leukemia in children[J]. Journal of Clinical Pediatrics, 2024, 42(7): 589-594.

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参考文献 16

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项目	结果
年龄[M(P₂₅~P₇₅)]/岁	10.0(2.0~15.0)
性别[n(%)]
男	18(69.2)
女	8(30.8)
初诊白细胞计数[M(P₂₅~P₇₅)]/×10⁹·L^-1	20.0(1.2~321.0)
初诊血红蛋白计数[M(P₂₅~P₇₅)]/g·L^-1	79.0(31.0~111.0)
初诊血小板计数[M(P₂₅~P₇₅)]/×10⁹·L^-1	42.0(12.0~143.0)
FAB分型[n(%)]
M0	1(3.8)
M2	15(57.7)
M4	1(3.8)
M5	9(34.6)
融合基因[n(%)]
RUNX1-RUNX1T1	12(46.2)
CBFβ-MYH11	1(3.8)
KMT2A-MLLT3	1(3.8)
NUP98-NSD1	1(3.8)
TLS-ERG	1(3.8)
EP300-ETV6	1(3.8)
无融合基因	9(34.6)
细胞遗传学风险分层[n(%)]
低危	14(53.8)
中高危	12(46.2)
CNSL[n(%)]	2(7.7)
疾病状态[n(%)]
复发	17(65.4)
难治	9(34.6)

病例类型	治疗前骨髓或髓外情况	例数	治疗后骨髓或髓外情况	ORR
复发	NR	11	7例CR（3例MRD转阴），2例PR，1例NR，1例未评估	90.0%
	PR	5	3例CR（2例MRD转阴），2例PR	60.0%
	睾丸白血病	1	睾丸体积明显缩小	100%
难治	NR	3	2例CR（1例MRD转阴），1例NR	66.7%
难治	PR	6	6例CR（1例MRD转阴）	100%

不良反应	例数[n(%)]
骨髓抑制	26(100)
感染	15(57.7)
脓毒症	6(23.1)
口腔感染	6(23.1)
上呼吸道感染	4(15.4)
肛周感染	4(15.4)
肺部感染	2(7.7)
急性腮腺炎	1(3.8)
急性腹膜炎	1(3.8)
疱疹病毒感染	2(7.7)
趾甲沟炎	1(3.8)
出血	5(19.2)
转氨酶升高	9(34.6)
胃肠道反应	26(100)
治疗相关死亡	1(3.8)