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Pediatr Blood Cancer. 2016 Sep;63(9):1539-45. doi: 10.1002/pbc.26045. Epub 2016 May 10.

Association Between Combined Presence of Hepatitis C Virus and Polymorphisms in Different Genes With Toxicities of Methotrexate and 6-Mercaptopurine in Children With Acute Lymphoblastic Leukemia.

Author information

1
Department of Clinical Pharmacy, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
2
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
3
Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
4
Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
5
Department of Pediatrics, Hematology-Oncology Division, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.

Abstract

BACKGROUND:

The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL).

PROCEDURE:

One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records.

RESULTS:

There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases.

CONCLUSIONS:

The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.

KEYWORDS:

HCV; acute lymphoblastic leukemia; chemotherapy; children; genetic polymorphism; toxicities

PMID:
27163515
DOI:
10.1002/pbc.26045
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