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目的探讨不同水化量对大剂量甲氨蝶呤(HD-MTX)血药浓度的影响,以及与不良反应的关系。方法以完成诱导、巩固阶段化疗后拟进入庇护所治疗的ALL患儿和非霍奇金淋巴瘤患儿为研究对象;采用自身对照的设计方案;每例患儿给予3、4次HD-MTX化疗,每例每次5 g.m-2,每例次的水化量分别为5 000 mL.m-2.d-1(5 L组)、4 000 mL.m-2.d-1(4 L组)和3 000 mL.m-2.d-1(3 L组),碱化量及四氢叶酸钙解救量均恒定。每例次化疗于开始用药后0 h、24 h、36 h、42 h、48 h、54 h采集外周静脉血样,并于开始用药后2 h(三联鞘注前)行腰椎穿刺留取脑脊液标本,用高效液相色谱分析仪测定其MTX浓度。结果12例患儿共进行了42例次HD-MTX化疗,共测定血药浓度238次。不同水化组之间各时间点的血药浓度相互比较,24 h MTX血药浓度测得值3 L组显著高于4 L组和5 L组,其不良反应无统计学差异。结论HD-MTX化疗时水化量的多少对MTX的血药浓度有一定的影响,尤其在开始用药后36 h内,二者成反比关系。化疗后的不良反应在3 000~5 000 mL.m-2.d-1水化量范围内无统计学差异。
Objective To investigate the effect of different hydration levels on the blood concentration of high-dose methotrexate (HD-MTX) and its relationship with adverse reactions. Methods The children with ALL and non-Hodgkin’s lymphoma who were enrolled in asylum after completion of induction and consolidation phase chemotherapy were enrolled in this study. The self-control design was used. Each patient was given 3,4 HD-MTX Chemotherapy, each with 5 gm-2, the amount of hydration in each case were 5 000 mL.m-2.d-1 (5 L), 4 000 mL.m-2.d-1 L group) and 3 000 mL.m-2.d-1 (3 L group). The amounts of alkalinization and calcium leucovorin rescue were all constant. Peripheral blood samples were collected at 0, 24, 36, 42, 48, 54 hours after the start of chemotherapy in each case of chemotherapy, and cerebrospinal fluid specimens were obtained by lumbar puncture 2 hours after the start of medication , And its MTX concentration was measured by high performance liquid chromatography. Results A total of 42 HD-MTX chemotherapies were performed in 12 patients. The blood concentration was determined 238 times. The blood concentration of different hydration groups at different time points compared with each other, 24 h MTX blood concentration measured 3 L group was significantly higher than the 4 L group and 5 L group, the adverse reaction was not statistically different. Conclusion The amount of hydration in HD-MTX chemotherapy has a certain impact on the plasma concentration of MTX, especially in the first 36 hours after treatment, the two are inversely proportional relationship. Adverse reactions after chemotherapy in the 3 000 ~ 5 000 mL.m-2.d-1 hydration within the range of no significant difference.