Influence of plasma methotrexate level and MTHFR genotype in Korean paediatric patients with acute lymphoblastic leukaemia

Abstract

Whether plasma MTX concentrations and MTHFR C677T and A1298C polymorphisms could be used as a predictor of occurrence of MTX-related toxicities in Korean paediatric patients with acute lymphoblastic leukaemia (ALL) were assessed. HD-MTX related toxicities, MTHFR polymorphisms and MTX plasma concentrations following 337 HD-MTX cycles to 117 children with ALL on maintenance therapy were analyzed. A significantly higher frequency of hyperbilirubinemia (P = 0.0443) and renal toxicity (P = 0.0107) were associated with high MTX concentrations by Fisher’s exact test. Moreover, high MTX concentrations at 24 h, 48, and 72 h were significantly associated with increased frequency of vomiting (P < 0.05) and hyperbilirubinemia (P < 0.05) by Mann-Whitney U test. There was a significantly higher frequency of mucositis in patients with the MTHFR 677 TT genotype (P = 0.0273) and a significantly higher frequency of MTX dose reduction in patients with the 677 TT genotype (P = 0.0217), compared to the CC/CT genotype. Independently, plasma MTX concentrations and MTHFR C677T genotype could be useful markers for tailoring MTX dosing and monitoring adverse effects in childhood ALL HD-MTX therapy in Korean patients.

Keywords:

• Methotrexate
• MTHFR
• Korean pediatric patients
• Acute lymphoblastic leukemia
• Toxicity
• Polymorphism

Disclosure statement

The authors declare no competing interests.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Notes on contributors

Hyojin Chae

Hyojin Chae, MD, PhD, Associate Professor, Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea. Dr. Chae’s main interests include clinical chemistry, pharmacokinetics and pharmacogenetics.

Myungshin Kim, MD, PhD, Professor, Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea. Catholic Genetic Laboratory Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea. Dr. Kim is the Chief of the Catholic Genetic Laboratory Center and Center for Applied Genomics & Precision Medicine. Her main interests include genomics in medicine, rare disease, diagnostic hematology and cell therapy.

Sun Hee Choi, RN, PhD, Nurse Choi was previously the Head Nurse for the pediatric chemotherapy and hematopoietic cell transplantation ward at Seoul Saint Mary’s Hospital, The Catholic University of Korea. Her chief research interests include the key role of nursing in the care of the pediatric hematology/oncology patient.

Seongkoo Kim, MD, Clinical Assistant Professor, Department of Pediatrics, Seoul Saint Mary’s Hospital, The Catholic University of Korea. Dr. Kim’s main interests include pediatric leukemias, and hematopoietic cell transplantation.

Jae Wook Lee, MD, PhD, Associate Professor, Department of Pediatrics, Seoul Saint Mary’s Hospital, The Catholic University of Korea. Dr. Lee’s main interests include pediatric leukemias, and hematopoietic cell transplantation.

Nack-Gyun Chung, MD, PhD, Professor, Department of Pediatrics, Seoul Saint Mary’s Hospital, The Catholic University of Korea. Dr. Chung is the Chief of the Division of Hematology and Oncology, Department of Pediatrics, The Catholic University of Korea. His main interests include pediatric leukemias, bone marrow failure and hematopoietic cell transplantation.

Bin Cho, MD, PhD, Professor, Department of Pediatrics, Seoul Saint Mary’s Hospital, The Catholic University of Korea. Dr. Cho is the Chief of the Department of Pediatrics, The Catholic University of Korea. His main interests include pediatric leukemias and hematopoietic cell transplantation.

Yonggoo Kim, MD, PhD, Professor, Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea. Catholic Genetic Laboratory Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea. Dr. Kim’s main interests include diagnostic hematology, genetics and cell therapy.