Xu Wei-qun, Tang Yong-min, Fang Cheng-qing, Song Hua, Shi Shu-wen, Yang Shi-long, Ren Ding-tai, Shen Hong-qiang, Qian Bai-qin
Division of Hematology and Oncology, Children's Hospital of Zhejiang University, School of Medicine, Hangzhou 310003, China.
Zhonghua Xue Ye Xue Za Zhi. 2005 Jan;26(1):15-8.
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.
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/m2 vs 5 g/m2) 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.
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).
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 approximately 5 g/m2 but there are individual differences.
观察大剂量甲氨蝶呤（HDMTX）治疗中清除延迟的发生率、副作用及其对下一疗程化疗的影响，并分析甲氨蝶呤剂量、输注时间与清除延迟发生率之间的关系。
本研究分析了121例儿童急性淋巴细胞白血病（ALL）患者（共497次HDMTX输注）。比较不同剂量组（3g/m² vs 5g/m²）和不同输注时间组（7小时 vs 24小时）的清除延迟率及不良反应。不良反应评价依据世界卫生组织（WHO）毒性分级标准。通过亚叶酸钙（CF）/甲氨蝶呤指数比较各组CF的解救剂量。
清除延迟的总体发生率为12.1%，首次发生的相对风险为30.6%。第二次发生的相对风险增至45.9%（P<0.01），第三次发生时未显著增加（35.3%）。发生清除延迟的儿童血小板计数较低（P<0.01），CF解救剂量较高（P<0.01），口腔黏膜损伤更严重（P<0.05），3g组下一疗程化疗中位推迟4天。3g组和5g组之间（12.1% vs 12.0%，P>0.05）以及甲氨蝶呤7小时和24小时输注组之间（13.6% vs 11.9%，P>0.05）清除延迟率无显著差异。5g组唯一出现的副作用是胃肠道不良反应。未发生清除延迟的5g组CF/甲氨蝶呤指数低于3g组（P<0.01）。
HDMTX治疗中的清除延迟伴有骨髓抑制和口腔黏膜损伤，需要更多CF解救，并会推迟后续化疗疗程。清除延迟与输注时间及3至5g/m²范围内的甲氨蝶呤剂量无关，但存在个体差异。
