Effect of ITPA Polymorphism on Adverse Drug Reactions of 6-Mercaptopurine in Pediatric Patients with Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

6-Mercaptopurine (6-MP) is a cornerstone of the maintenance regimen for pediatric acute lymphoblastic leukemia (ALL). Inosine triphosphate pyrophosphatase (ITPA) is considered a candidate pharmacogenetic marker that may affect metabolism and 6-MP-induced toxicities; however, the findings are inconsi...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-03, Vol.15 (4), p.416
Main Authors: Lee, Yeonhong, Jang, Eun Jeong, Yoon, Ha-Young, Yee, Jeong, Gwak, Hye-Sun
Format: Article
Language:English
Subjects:
6-mercaptopurine
adverse drug reactions
Ethnicity
inosine triphosphate pyrophosphatase
ITPA 94C>A
Leukemia
Leukopenia
Meta-analysis
Metabolism
Metabolites
Neutropenia
Pediatrics
Polymorphism
Sensitivity analysis
Systematic Review
Toxicity
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Summary:6-Mercaptopurine (6-MP) is a cornerstone of the maintenance regimen for pediatric acute lymphoblastic leukemia (ALL). Inosine triphosphate pyrophosphatase (ITPA) is considered a candidate pharmacogenetic marker that may affect metabolism and 6-MP-induced toxicities; however, the findings are inconsistent. Therefore, we attempted to evaluate the effect of ITPA 94C>A polymorphism on 6-MP-induced hematological toxicity and hepatotoxicity through a systematic review and meta-analysis. A literature search for qualifying studies was conducted using the PubMed, Web of Science, and Embase databases until October 2021. Overall, 10 eligible studies with 1072 pediatric ALL patients were included in this meta-analysis. The results indicated that ITPA 94C>A was significantly associated with 6-MP-induced neutropenia (OR 2.38, 95% CI: 1.56−3.62; p = 0.005) and hepatotoxicity (OR 1.98, 95% CI: 1.32−2.95; p = 0.0009); however, no significant association was found between the ITPA 94C>A variant and 6-MP-induced leukopenia (OR 1.75, 95% CI: 0.74−4.12; p = 0.20). This meta-analysis demonstrated that ITPA 94C>A polymorphism could affect 6-MP-induced toxicities. Our findings suggested that ITPA genotyping might help predict 6-MP-induced myelosuppression and hepatotoxicity.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15040416