大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病甲氨蝶呤排泄延迟的影响因素及患儿预后分析  

Influencing factors of delayed elimination of methotrexate in children with acute lymphoblastic leukemia treated by high-dose methotrexate and their prognostic analysis

作　　者：崔东艳 徐雨婷 刘璐 刘爱国[1] 张艾[1] 王雅琴[1] 胡群[1] Cui Dongyan;Xu Yuting;Liu Lu;Liu Aiguo;Zhang Ai;Wang Yaqin;Hu Qun(Department of Pediatric Hematology and Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Pharmacy,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Hematology,Children's Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]华中科技大学同济医学院附属同济医院儿童血液病专科,武汉430030 [2]华中科技大学同济医学院附属同济医院药学部,武汉430030 [3]复旦大学附属儿科医院血液科,上海201102

出　　处：《白血病．淋巴瘤》2022年第10期587-592,共6页Journal of Leukemia & Lymphoma

基　　金：CCCG-ALL2015多中心协作项目(WHTJ-2015043)。

摘　　要：目的:探讨儿童急性淋巴细胞白血病(ALL)大剂量甲氨蝶呤(HD-MTX)治疗后甲氨蝶呤(MTX)排泄延迟的影响因素及MTX排泄延迟、HD-MTX减量对患儿预后的影响。方法:回顾性分析2015年1月至2020年6月于华中科技大学同济医学院附属同济医院按照中国抗癌协会小儿肿瘤专业委员会(CCCG)-ALL 2015方案诊治的242例ALL患儿的临床资料,其中低危、中高危患儿分别接受3、5 g/m^(2) MTX化疗4次,监测血清MTX浓度,以给药44 h血清MTX浓度>1μmol/L为排泄延迟,并分为轻度(>1μmol/L且≤5μmol/L)、中度(>5μmol/L且≤10μmol/L)和重度(>10μmol/L)排泄延迟。采用单因素及多因素logistic回归分析MTX排泄延迟的影响因素,采用单因素Cox比例风险模型分析患儿复发的相关因素。结果:242例ALL患儿共完成962例次HD-MTX化疗,给药44 h血清中位MTX浓度[M(Q1,Q3)]为0.45μmol/L(0.33μmol/L,0.72μmol/L),MTX排泄延迟总发生率为17.7%(170/962),轻、中、重度排泄延迟发生率分别为13.8%(133/962)、2.6%(25/962)、1.2%(12/962)。logistic回归分析结果显示,年龄≥7岁(OR=1.68,95%CI 1.17~2.41,P=0.005)、单次MTX剂量>3 g/m^(2)(OR=2.14,95%CI 1.52~3.03,P<0.001)及首次HD-MTX化疗(OR=2.05,95%CI 1.43~2.93,P<0.001)为MTX排泄延迟的独立危险因素。中位随访50个月(34个月,68个月),12.8%(31/242)患儿复发,中位复发时间30个月(30个月,39个月)。单因素Cox回归分析结果显示,不同性别、免疫表型、危险度、MTX排泄延迟发生次数、HD-MTX化疗完成度(MTX平均剂量与初始计划剂量的比值)患儿复发率差异均无统计学意义(均P>0.05)。结论:ALL患儿发生MTX排泄延迟的独立危险因素有年龄≥7岁、单次MTX剂量>3 g/m^(2)及首次HD-MTX化疗,MTX排泄延迟及HD-MTX减量对疾病复发无明显影响。Objective:To investigate the influencing factors of delayed methotrexate (MTX) elimination after high-dose methotrexate (HD-MTX) treatment in children with acute lymphoblastic leukemia (ALL) and the effects of delayed MTX elimination and HD-MTX reduction on the prognosis of children with ALL.Methods:The clinical data of 242 children with ALL diagnosed and treated in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2015 to June 2020 in accordance with the Chinese Children's Cancer Group study ALL 2015 (CCCG-ALL 2015) were retrospectively analyzed. Low risk and intermediate/high risk children respectively received 3 g/m^(2) and 5 g/m^(2) HD-MTX for 4 times, and the serum MTX concentration was monitored. The serum MTX concentration > 1 μmol/L at 44 h of administration was considered as the delayed elimination, which was divided into mild (> 1 μmol/L and ≤ 5 μmol/L), moderate (> 5 μmol/L and ≤ 10 μmol/L) and severe (> 10 μmol/L) delayed elimination. Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of delayed MTX elimination, and univariate Cox proportional hazards model was used to analyze the related factors of ALL relapse. Results:The 242 children with ALL completed 962 times of HD-MTX chemotherapy. The median serum MTX concentration [ M ( Q1, Q3)] at 44 h of administration was 0.45 μmol/L (0.33 μmol/L, 0.72 μmol/L). The total incidence of delayed MTX elimination was 17.7% (170/962). The incidence of mild, moderate and severe delayed elimination was 13.8% (133/962), 2.6% (25/962) and 1.2% (12/962), respectively. Logistic regression analysis showed that age ≥ 7 years old ( OR = 1.68, 95% CI 1.17-2.41, P = 0.005), MTX dose >3 g/m^(2) at each course ( OR = 2.14, 95% CI 1.52-3.03, P < 0.001) and the first course of HD-MTX chemotherapy ( OR = 2.05, 95% CI 1.43-2.93, P < 0.001) were independent risk factors for delayed MTX elimination. The median follow-up time was 50 months (34 months, 68 months), 1

关 键 词：白血病 淋巴样 儿童 甲氨蝶呤 药物监测 复发 药物排泄延迟 

分 类 号：R733.71[医药卫生—肿瘤]