Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
J Rheumatol. 2010 Mar;37(3):485-90. doi: 10.3899/jrheum.090834. Epub 2010 Jan 15.
Azathioprine is widely used in patients with autoimmune diseases and after organ allografting. A recognized carcinogen, azathioprine is also associated with the development of therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML).
In 56 reported cases, azathioprine had been administered for a median of 65 months (range 6-192) to a median cumulative dose of 146 g (range 19-750) before t-MDS/AML developed.
In 11 patients, repeated episodes of cytopenias developed during azathioprine therapy, ante-dating the development of t-MDS/AML. In 33 cases with successful karyotypic analysis, 26 cases (79%) showed monosomy 7, deletion of the long arm of chromosomes 7 and 5, and rearrangement of chromosome 11q23. These changes were cytogenetic hallmarks of MDS/AML secondary to known leukemogenic agents and radiotherapy.
The observations implicate azathioprine as a leukemogenic agent. It will be prudent to review the need for azathioprine therapy when unexpected cytopenias occur and prescription has been prolonged.
硫唑嘌呤被广泛用于治疗自身免疫性疾病和器官移植后患者。作为一种公认的致癌物质，硫唑嘌呤也与治疗相关骨髓增生异常综合征和急性髓系白血病（t-MDS/AML）的发展有关。
在报告的 56 例病例中，t-MDS/AML 发生前，硫唑嘌呤的中位治疗时间为 65 个月（范围 6-192），中位累积剂量为 146g（范围 19-750）。
在 11 例患者中，在硫唑嘌呤治疗期间反复出现细胞减少症，早于 t-MDS/AML 的发生。在成功进行核型分析的 33 例病例中，26 例（79%）出现 7 号染色体单体、7 号和 5 号染色体长臂缺失以及 11q23 号染色体易位。这些变化是由已知的致白血病剂和放疗引起的 MDS/AML 的细胞遗传学特征。
这些观察结果表明硫唑嘌呤是一种致白血病剂。当出现意外的细胞减少症且处方延长时，应谨慎评估是否需要继续使用硫唑嘌呤治疗。
Zotero 插件