大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病排泄延迟分析  

Study on elimination delay in high dose methotrexate therapy in childhood acute lymphoblastic leukemia

作　　者：徐卫群[1] 汤永民[1] 方澄清[1] 宋华[1] 石淑文[1] 扬世隆[1] 任鼎泰[1] 沈红强[1] 钱伯芹[1] 

机构地区：[1]浙江大学医学院附属儿童医院,杭州310003

出　　处：《中华血液学杂志》2005年第1期15-18,共4页Chinese Journal of Hematology

摘　　要：目的观察儿童急性淋巴细胞白血病(ALL)大剂量甲氨蝶呤(HDMTX)疗法MTX排泄延迟的发生率和不良反应,探讨MTX排泄延迟与MTX剂量、用药方式的关系,及如何减少排泄延迟的发生。方法分析121例497例次儿童ALLHDMTX化疗的临床资料,比较有和无排泄延迟情况下HDMTX的不良反应。并按剂量(3g组和5g组)和用药持续时间(7h组和24h组)分组,比较排泄延迟的发生率、不良反应及各组四氢叶酸钙(CF)的解救剂量。结果总体排泄延迟发生率为12.1%,发生1次排泄延迟的相对概率是30.6%,再次发生的相对概率为45.9%,明显增加(P<0.01)。有排泄延迟的患儿排泄延迟时血小板较无排泄延迟时明显减低(P<0.01),CF解救剂量明显增加(P<0.01)。3g组排泄延迟时口腔黏膜损害较无排泄延迟时更明显(P<0.05),下一疗程化疗延迟(中位延迟4d)。3g组排泄延迟发生率(12.1%)与5g组(12.0%)比较差异无统计学意义(P>0.05),7h用药组排泄延迟发生率(13.6%)与24h用药组(11.9%)比较差异也无统计学意义(P>0.05)。无排泄延迟时5g组仅胃肠道反应较3g组明显增加(P<0.01),而CF解救剂量明显低于3g组(P<0.01)。结论HDMTX排泄延迟情况下骨髓抑制和口腔黏膜损害的不良反应增加,下一疗程化疗延迟,CF用量增加。HDMTX排泄延迟在3～5g/m2剂量范围里与MTX剂量、用药方式无关。Objective To observe the incidence of elimination delay in high dose methotrexate ^(HDMTX) therapy, its side effects and influence to next course of chemotherapy and analyze the relationship between the dosage, the duration of MTX infusion and the morbidity of the elimination delay. Methods A total of 121 childhood acute lymphoblastic leukemia (ALL) (497 infusions of HDMTX) were analysed in this study. The elimination delay rate and the adverse effects in different dose groups (3 g/m^2 vs 5 g/m^2 ) and different infusion duration groups (7 h vs 24 h) were compared. The adverse effect evaluation was based on the World Health Organization (WHO) Toxicity Grading Criteria. The rescue dosages of calcium folinate (CF) among these groups were compared through CF/MTX index. Results The overall morbidity of elimination delay was 12.1% with a relative risk of 30.6% for the first time. The relative risk for the second time of occurrence was increased to 45.9% (P<0.01) and it was not significantly increased for the third time (~35.3% ). Children with elimination delay had lower platelet count (P<0.01) and higher CF rescue dosage (P<0.01), while the damage of oral mucous membrane was more severe (P<0.05) and the next course of chemotherapy would be postponed for a median of 4 days in 3 g group. There was no significant difference in elimination delay rates between 3 g and 5 g groups (12.1% vs 12.0%, P>0.05), and between 7 h and 24 h MTX infusion groups (13.6% vs 11.9%, P>0.05). The only side effect occurred in 5 g group was gastrointestinal morbidity. The CF/MTX index of 5 g group without elimination delay was less than that of 3 g group (P<0.01). Conclusion Elimination delay in HDMTX therapy accompanies the suppression of bone marrow and damage of oral mucous membrane, which need more CF rescues and will postpone the following course of chemotherapy. Elimination delay is not associated with the duration of the infusion and the dosage of MTX within the range of 3～5 g/m^2 but there are individual differences.

关 键 词：排泄 发生率 剂量 不良反应 迟发 儿童急性淋巴细胞白血病 治疗 损害 

分 类 号：R733.7[医药卫生—肿瘤]