AI Article Synopsis
- The study assessed how specific genetic polymorphisms (rs11045879 and rs4149056) impact the elimination and side effects of high-dose methotrexate (MTX) in children with leukemia.
- Carriers of the rs11045879C variant showed increased MTX levels in the blood after 96 hours and took longer to eliminate the drug, while those with the rs4149056C variant needed more doses of leucovorin to counteract MTX toxicity compared to non-carriers.
- The findings suggest that genetic testing could help tailor MTX treatment, potentially reducing harmful toxicities like thrombocytopenia and renal issues.
Article Abstract
To evaluate the association between polymorphisms and elimination/toxicities of high-dose methotrexate (MTX). rs11045879 and rs4149056 polymorphisms were retrospectively genotyped in 301 children with newly diagnosed acute lymphoblastic leukemia. MTX concentration, doses of leucovorin rescue and toxicities were recorded. rs11045879C carriers (CC + CT) had higher plasma MTX levels at 96 hr, and longer MTX elimination time. The number of leucovorin rescue doses in rs4149056C carriers (CC + CT) was more than those in TT ones. Moreover, polymorphisms were associated with HDMTX toxicities including thrombocytopenia, renal toxicity and anal mucositis, but not associated with MTX level at other time points or delayed elimination. Our data demonstrate that genotyping of might be useful to optimize MTX therapy.
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| http://dx.doi.org/10.2217/pgs-2022-0098 | DOI Listing |
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