Association of ABCC2 with levels and toxicity of methotrexate in Malaysian Childhood Acute Lymphoblastic Leukemia (ALL). (2nd April 2020)

• Record Type: Journal Article
• Authors: Razali, Rizal Husaini; Noorizhab, Mohd Nur Fakhruzzaman; Jamari, Hisyam; James, Richard Johari; Teh, Kok Hoi; Ibrahim, Hishamshah Mohd; Teh, Lay Kek; Salleh, Mohd Zaki
• Is Part Of: Pediatric hematology and oncology. Volume 37:Number 3(2020)
• Page Start: 185
• Page End: 197
• Publication Date: 2020-04-02
• Subjects: ABCC2 -- acute lymphoblastic leukemia -- ARID5B -- childhood -- methotrexate; Pediatric hematology -- Periodicals; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Hematologic Diseases -- Child; Hematologic Diseases -- Infant; Neoplasms -- Child; 618.9215
• DOI: 10.1080/08880018.2019.1705949
• Languages: English
• ISSNs: 0888-0018

Abstract

Abstract: Studies had shown that genetic polymorphism plays a significant role in the pharmacokinetics and pharmacodynamics variation of high dose methotrexate (MTX), 5000 mg/m 2 regimen. The objective of this study was to investigate the genetic variations associated with the serum level and toxicity of MTX in Malaysian children with acute lymphoblastic leukemia (ALL). Thirty-eight patients were genotyped for rs717620 ( ABCC2 ), rs4948496 ( ARID5B ), rs1801133 ( MTHFR ) and rs4149056 ( SLCO1B1 ). Serum levels of MTX at 48 h post 24 h of intravenous infusion were analyzed by high - performance liquid chromatography - mass spectrometry. The ABCC2 genotype was significantly associated with the serum levels of MTX at 48 h after treatment ( p = 0.017). Patients with CT and TT of rs717620 ( ABCC2 ) and TC and CC of rs4948496 ( ARID5B ) were significantly associated with leukopenia grade I–IV (Fisher Exact Test; p = 0.03 and 0.02, respectively). The three most common MTX related toxicities were leukopenia (60.5%), increased alanine aminotransferase enzyme (47.4%), and thrombocytopenia (47.4%). Our results demonstrate that by prescreening of patients for ABCC2 and ARID5B associated with the serum levels and adverse effects of MTX would identify patients at risk and therefore help a pediatric oncologist to personalize chemotherapy drugs for precision health.