Volume 5 • Issue 1 • 1000134
J Biomol Res Ther
ISSN: 2167-7956 JBMRT, an open access journal
Open Access Research Article
Bhinder et al., J Biomol Res Ther 2015, 5:1
DOI: 10.4172/2167-7956.1000134
Keywords: Methotrexate; Pharmacogenetic testing; Leukemia
Introduction
Te ideal target of pharmacotherapy is to have optimal clinical
outcomes, characterized by the complete treatment of a health illness
with minimal adverse efects. As of today, is this possible? Until
recently, health care providers had no idea why certain patients have
a positive response to a drug therapy while others experience side
efects from same therapy. It is known that patients can achieve better
results when receiving individualized treatment, possibly because
individualized medicine requires that one seeks a deep understanding
on how medicine is metabolized by an individual’s body. Although
clinical practice experience indicates that to be mostly true, how can
we assure the best health care of tomorrow?
A form of providing individualized care is called pharmacogenomics
or pharmacogenetics. As described by the FDA, “pharmacogenomics
allows one to identify sources of an individual’s profle of drug response
and predict the best possible treatment option for this individual. Te use
of genomic information has opened new possibilities in drug discovery
and development.” Te FDA provides a table of pharmacogenomics
biomarkers in drug label, in order to identify responders and non-
responders to medications, avoid adverse events, and optimize drug
dose. Drug label may contain information on genomic biomarkers and
can describe: drug exposure and clinical response variability, risk for
adverse events, genotype specifc dosing, mechanisms of drug action,
and polymorphic drug target and disposition genes. For example, due
to the fact that medications like codeine do not properly work for some
individuals, specifcally those considered ultra-rapid metabolizers for
CYP2D6; the FDA has issued boxed warnings with use for this specifc
population, including counseling information [1].
Tere are many studies proposing that, by selecting treatment
based on a patient’s specifc genes via pharmacogenetic testing,
we can predict the probability of success or failure of a particular
pharmacotherapy. Based on individual specifc genetic diferences,
pharmacogenetics can explain existing variability in drug response
from its metabolism to adverse reactions. Methotrexate is commonly
used as a chemotherapeutic agent for childhood acute lymphoblastic
leukemia (ALL), amongst other diseases. However, treatment is limited
due to severe toxicity or low efcacy of treatment for certain patients.
Methotrexate has been shown to exhibit diferent responses based on
the genetic expressions and variations of the genes SLC19A, SHMT,
ABCB1, ATIC and MTHFR. For this literature evaluation, we examined
the clinical relevance of pharmacogenetics testing for leukemia patients
treated with Methotrexate. Furthermore, the treatment outcome for
*Corresponding author: Mohammad S Shawaqfeh, Pharm D, Ph.D, Nova
Southeastern University, Palm Beach Gardens, FL, United States, Tel: 561-805-
2243; E-mail: mshawaqfeh@nova.edu
Received February 28, 2015; Accepted December 15, 2015; Published December
26, 2015
Citation: Bhinder MTM, Halum AS, Mufih SM, Shawaqfeh M (2015) Pharmacogenetic
Testing for Methotrexate Treatment in Leukemia Patients. J Biomol Res Ther 4: 134.
doi:10.4172/2167-7956.1000134
Copyright: © 2015 Bhinder MTM, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Abstract
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 effcacious 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 signifcant 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.
Pharmacogenetic Testing for Methotrexate Treatment in Leukemia
Patients
Muhammad Tahir M Bhinder, Amin Saleh Halum, Suhaib M Mufih and Mohammad Shawaqfeh
1
*
College of Pharmacy, Nova Southeastern University, FL, USA
Journal of
Biomolecular Research & Therapeutics
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ISSN: 2167-7956