Effects of <i>SLCO1B1</i> on elimination and toxicities of high-dose methotrexate in pediatric acute lymphoblastic leukemia-Reference-Cited by-同舟云学术

Effects of SLCO1B1 on elimination and toxicities of high-dose methotrexate in pediatric acute lymphoblastic leukemia

Published:2022-10 Issue:15 Volume:23 Page:821-834
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Yang Fei-Fei¹,Xue Tian-Lin²,Gao Chao²,Wu Ying¹,Lin Wei¹,Li Jun²,Zhang Rui-Dong¹,Zheng Hu-Yong¹,Liu Shu-Guang²^ORCID

Affiliation:

1. Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China

2. Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China

Abstract

Aim: To evaluate the association between SLCO1B1 polymorphisms and elimination/toxicities of high-dose methotrexate (MTX). Methods: SLCO1B1 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. Results: SLCO1B1 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, SLCO1B1 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. Conclusions: Our data demonstrate that genotyping of SLCO1B1 might be useful to optimize MTX therapy.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2022-0098

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