CONGENITAL THIOPURINE METHYLTRANSFERASE DEFICIENCY AND 6-MERCAPTOPURINE TOXICITY DURING TREATMENT FOR ACUTE LYMPHOBLASTIC-LEUKEMIA
CONGENITAL THIOPURINE METHYLTRANSFERASE DEFICIENCY AND 6-MERCAPTOPURINE TOXICITY DURING TREATMENT FOR ACUTE LYMPHOBLASTIC-LEUKEMIA
复制标题
DOI：
10.1136/adc.69.5.577
复制
发表时间：
1993-11-01
影响因子：
5.2
通讯作者：
LILLEYMAN, JS
中科院分区：
文献类型：
--
作者：
LENNARD, L;GIBSON, BES;LILLEYMAN, JS
两名患有急性淋巴细胞白血病（ALL）的儿童每天服用6-巯基嘌呤作为英国国家治疗试验的一部分，在标准方案剂量的25%时反复出现严重的骨髓抑制。发现两者都具有不可检测的细胞内巯基嘌呤甲基转移酶（TPMT）活性，TPMT是一种控制6-巯基嘌呤的主要替代分解代谢途径之一的酶，在方案剂量的10-25%时，两种患者产生的细胞毒性药物代谢物浓度均高于其他服用100%剂量的患者。缺乏TPMT的正常人群中。重要的是要认识到这样的人，以避免致命的骨髓衰竭，通过无意中过量，并确保足够的药物作用，可以达到约10%的标准剂量。
Two children with acute lymphoblastic leukaemia (ALL) taking daily 6-mercaptopurine as part of a national UK therapeutic trial repeatedly developed profound myelosuppression on 25% of the standard protocol dose. Both were found to have undetectable intracellular activity of thiopurine methyltransferase (TPMT), an enzyme controlling one of the major alternative catabolic pathways of 6-mercaptopurine, and both produced higher concentrations of cytotoxic drug metabolites at 10-25% of the protocol dose than other patients taking 100%.It is supposed that these patients represent the 0.33% of the normal population constitutionally lacking TPMT. It is important to recognise such individuals both to avoid fatal bone marrow failure through inadvertent overdosage, and to be reassured that an adequate drug effect can be achieved at around 10% of the standard dose.