UCSF Benioff Children's Hospital Oakland, Oakland, CA.
J Pediatr Hematol Oncol. 2022 Mar 1;44(2):e521-e525. doi: 10.1097/MPH.0000000000002313.
Persistently elevated absolute neutrophil counts during maintenance for acute lymphoblastic leukemia is a risk factor for relapse and may be related to wild-type thiopurine methyltransferase activity and overly efficient shunting of 6-mercaptopurine to hepatotoxic metabolites (6-methylmercaptopurine nucleotides), leading to low 6-thioguanine nucleotides. 6-mercaptopurine is also metabolized by xanthine oxidase, and therefore allopurinol, an inhibitor of xanthine oxidase, allows for increased 6-thioguanine nucleotides and decreased 6-methylmercaptopurine nucleotide. Here, we report our experience with allopurinol for persistently elevated absolute neutrophil count or hepatotoxicity and suggest an algorithmic approach for checking thiopurine metabolites and initiating allopurinol in acute lymphoblastic leukemia maintenance.
在急性淋巴细胞白血病的维持治疗期间，持续升高的绝对中性粒细胞计数是复发的危险因素，可能与野生型巯基嘌呤甲基转移酶活性和 6-巯基嘌呤向肝毒性代谢物（6-甲基巯基嘌呤核苷酸）的过度有效分流有关，导致 6-硫鸟嘌呤核苷酸水平降低。6-巯基嘌呤也可被黄嘌呤氧化酶代谢，因此，黄嘌呤氧化酶抑制剂别嘌醇可增加 6-硫鸟嘌呤核苷酸并减少 6-甲基巯基嘌呤核苷酸。在这里，我们报告了别嘌醇在持续升高的绝对中性粒细胞计数或肝毒性方面的应用经验，并提出了一种用于检查巯基嘌呤代谢物和启动急性淋巴细胞白血病维持治疗中别嘌醇的算法方法。
