Andersen J B, Szumlanski C, Weinshilboum R M, Schmiegelow K
Laboratory of Paediatric Haematology and Oncology, The Juliane Marie Centre, State University Hospital, Copenhagen, Denmark.
Acta Paediatr. 1998 Jan;87(1):108-11. doi: 10.1080/08035259850158001.
Two children with acute lymphoblastic leukaemia (ALL) were found to be thiopurine methyltransferase (TPMT)-deficient by both genotype and phenotype. They were monitored with haematological parameters and red blood cell concentrations of 6-thioguanine nucleotides (E-6TGN) and methotrexate (E-MTX, including MTX polyglutamates), in relation to the doses of 6-mercaptopurine (6MP) and methotrexate (MTX), during their maintenance chemotherapy. Both patients developed severe pancytopenia at the standard protocol dose of 6MP. Even at 25% and 5%, respectively, of the protocol dose of 6MP, they achieved E-6TGN values several-fold above the population median, but without unacceptable bone-marrow toxicity. Their high E-6TGN values had only a minor influence on their E-MTX values and their tolerance to oral MTX, but severe pancytopenia followed high-dose MTX infusions. Due to the risk of fatal myelosuppression we recommend up-front determination of TPMT activity in patients treated with 6MP or azathioprine.
两名急性淋巴细胞白血病（ALL）患儿经基因型和表型检测均发现硫嘌呤甲基转移酶（TPMT）缺乏。在维持化疗期间，对他们进行了血液学参数监测，并检测了红细胞中6-硫鸟嘌呤核苷酸（E-6TGN）和甲氨蝶呤（E-MTX，包括甲氨蝶呤多聚谷氨酸盐）的浓度，这些指标与6-巯基嘌呤（6MP）和甲氨蝶呤（MTX）的剂量相关。两名患者在标准方案剂量的6MP治疗下均出现了严重的全血细胞减少。即使分别给予6MP方案剂量的25%和5%，他们的E-6TGN值仍比总体中位数高出数倍，但未出现不可接受的骨髓毒性。他们较高的E-6TGN值对其E-MTX值及口服MTX耐受性影响较小，但高剂量MTX输注后出现了严重的全血细胞减少。鉴于存在致命性骨髓抑制的风险，我们建议在接受6MP或硫唑嘌呤治疗的患者中预先测定TPMT活性。
