Журнал биомолекулярных исследований и терапии

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Pharmacogenetic Testing for Methotrexate Treatment in Leukemia Patients

Muhammad Tahir M Bhinder, Amin Saleh Halum, Suhaib M Muflih and Mohammad Shawaqfeh

Background: Pharmacogenetic testing can be used as a means to individualize a patient’s medical regimen in order to prevent future adverse drug events. Pharmacogenomics looks at individual genes and can predetermine a patient’s susceptibility to certain side effects of medications, as well as how efficacious a medication will be for that patient. Methotrexate has been shown to exhibit different responses based on the genetic expressions and variations of the genes SLC19A, SHMT, ABCB1, ATIC and MTHFR.

Objective: To determine the clinical relevance of pharamcogenetic testing for leukaemia patients treated with Methotrexate.

Method: A systematic review was conducted from September 2013-August 2015, primarily using the EMBASE and PubMed databases, identifying Cochrane reviews, controlled clinical trials, randomized control trials, meta-analyses and systematic reviews. Search terms that were initially included were the name of the genes individually (SLC19A, SHMT, ABCB1, ATIC and MTHFR), methotrexate, and leukemia. The results were further limited to English and those conducted on humans. Two reviewers extracted data and evaluated pertinent studies. A total of 82 articles were found, but were then narrowed down to 34 articles. The 34 articles were graded with the JADAD scale, with scores ranging from of 0-5 points. They were then evaluated for clinical relevance, and were reduced to 10 articles to be analysed for the purpose of the study.

Results: Of the 34 article graded, 26 articles had a score of 0 points.

Conclusion: Although there is significant evidence of an association between the clinical effects of methotrexate in leukemia patients and these genes, based on their JADAD scores, there appears to be a lack of high evidence clinical studies. None of the article found included randomized controlled trials, despite compelling evidence indicating a need for these high quality studies in order to administer methotrexate to patients in a safer manner.