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本文报告的118例小儿急性淋巴细胞白血病用常规诱导化疗方案已获完全缓解,并且用 MTX 鞘内注射以及头部照射以预防脑膜白血病。维持化疗包括用6-MP,1/日;MTX,1/周;VCR 1/月及强的松治疗。82例6-MP 和 MTX 在上午给药,36例在晚上给药。Kaplan-Meier’s 无病生存期认为在晚上化疗较好,回归分析证实了这点,其无病生存期为78周以上,上午给药比晚上给药的复发危险性高4.6倍以上。作者认为,维持化疗的时间作用不十分清楚,但在人类和鼠类生物规律的大多数研究中认为,代谢变化是受睡眠和活动的影响。在人类骨髓细胞毒性限于MTX 和6-MP 剂量的增大,正常骨髓细胞 DNA 合成作用在夜间最低,因此在晚上投予 MTX 和6-MP,正常细胞优于白血病细胞,白血病细胞 DNA 合成作用白天变化最小及不稳定。因为正常白细胞双氢叶酸的最大还原作用在夜间,所以能保护对 MTX 的毒性作用。上午投予口服维持化疗药还可能导致因伴随食物的摄取使之吸收更加不稳定,某些食物可产生血浆中短暂的嘌呤物质升高,可与6-MP 和 MTX 产生竞争
The 118 reported cases of pediatric acute lymphoblastic leukemia have been completely rehabilitated with conventional induction chemotherapy and MTX intrathecal injection and head irradiation have been used to prevent meningeal leukemia. Maintenance chemotherapy included 6-MP, 1/day; MTX, 1/week; VCR 1/month and prednisone. 82 cases of 6-MP and MTX were administered in the morning and 36 cases were administered in the evening. Kaplan-Meier’s disease-free survival was considered to be better at night, and regression analysis confirmed this, with a disease-free survival of 78 weeks or more, with a risk of recurrence of 4.6 times higher in the morning than in the evening. The authors believe that the time to maintain chemotherapy is not very clear, but in most studies of human and rodent biology, it is believed that metabolic changes are affected by sleep and activity. Since the cytotoxicity of human bone marrow is limited to the increase of MTX and 6-MP doses, DNA synthesis of normal bone marrow cells is the lowest at night, so MTX and 6-MP are administered at night. Normal cells are better than leukemia cells, and DNA synthesis of leukemia cells is effective during the daytime. The changes are minimal and unstable. Because the maximum reduction of normal leukocyte dihydrofolate is at night, it can protect the toxic effects on MTX. Oral administration of chemotherapy drugs in the morning may also lead to more unstable absorption due to concomitant food intake. Certain foods may produce transient elevated purine levels in the plasma and may compete with 6-MP and MTX.