Effect of folate status and methylenetetrahydrofolate reductase genotypes on the complications and outcome of high dose methotrexate chemotherapy in north Indian children with acute lymphoblastic leukemia

Nirmalya Roy Moulik; Archana Kumar; Suraksha Agrawal; Abbas Ali Mahdi; Ashutosh Kumar

doi:10.4103/0971-5851.180144

Indian Journal of Medical and Paediatric Oncology, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2016; 37(02): 85-89
DOI: 10.4103/0971-5851.180144

ORIGINAL ARTICLE

Effect of folate status and methylenetetrahydrofolate reductase genotypes on the complications and outcome of high dose methotrexate chemotherapy in north Indian children with acute lymphoblastic leukemia

Nirmalya Roy Moulik

Department of Pediatrics, Division of Pediatric Hematology/Oncology, King George's Medical University, Lucknow, Uttar Pradesh, India

,

Archana Kumar

Department of Pediatrics, Division of Pediatric Hematology/Oncology, King George's Medical University, Lucknow, Uttar Pradesh, India

,

Suraksha Agrawal

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

,

Abbas Ali Mahdi

Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India

,

Ashutosh Kumar

Department of Hematopathology, King George's Medical University, Lucknow, Uttar Pradesh, India

› Institutsangaben

Abstract

als PDF herunterladen

Abstract

Purpose: The genes of the folate metabolic pathway have been associated with toxicities during high dose methotrexate therapy for childhood ALL, however, the importance of intrinsic folate status in this regard is unclear. Methods: In the present study the effect of precourse folate levels and MTHFR genotypes on the complications during high dose methotrexate chemotherapy in children with ALL were examined. Results: Twenty-one children were studied. Folate deficiency was associated with higher incidence of neutropenia (P = 0.03) and longer duration of chemotherapy interruption (P = 0.009). Children with MTHFR1298 mutations needed more red cell transfusion (P = 0.03). All 3 deaths encountered were seen in folate deficient children. Conclusions: Folate deficiency was associated with higher complications during high dose methotrexate therapy, the implications of which are important especially in resource poor settings with high prevalence of folate deficiency.

Keywords

Childhood acute lymphoblastic leukemia - folate deficiency - high-dose methotrexate

PDF (536 kb)

Referenzen

References
1 Bostrom BC, Erdmann GR, Kamen BA. Systemic methotrexate exposure is greater after intrathecal than after oral administration. J Pediatr Hematol Oncol 2003;25:114-7.
2 Kapoor G, Sinha R, Abedin S. Experience with high dose methotrexate therapy in childhood acute lymphoblastic leukemia in a tertiary care cancer centre of a developing country. Pediatr Blood Cancer 2012;59:448-53.
3 Cohen IJ. Defining the appropriate dosage of folinic acid after high-dose methotrexate for childhood acute lymphatic leukemia that will prevent neurotoxicity without rescuing malignant cells in the central nervous system. J Pediatr Hematol Oncol 2004;26:156-63.
4 Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, Garcia-Orad A. A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia. Pharmacogenomics J 2013;13:498-506.
5 Robien K. Folate during antifolate chemotherapy: What we know... and do not know. Nutr Clin Pract 2005;20: 411-22.
6 Holmboe L, Andersen AM, Mørkrid L, Slørdal L, Hall KS. High dose methotrexate chemotherapy: Pharmacokinetics, folate and toxicity in osteosarcoma patients. Br J Clin Pharmacol 2012;73:106-14.
7 Valik D, Sterba J, Bajciova V, Demlova R. Severe encephalopathy induced by the first but not the second course of high-dose methotrexate mirrored by plasma homocysteine elevations and preceded by extreme differences in pretreatment plasma folate. Oncology 2005;69:269-72.
8 Imanishi H, Okamura N, Yagi M, Noro Y, Moriya Y, Nakamura T, et al. Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. J Hum Genet 2007;52:166-71.
9 Liu SG, Li ZG, Cui L, Gao C, Li WJ, Zhao XX. Effects of methylenetetrahydrofolate reductase gene polymorphisms on toxicities during consolidation therapy in pediatric acute lymphoblastic leukemia in a Chinese population. Leuk Lymphoma 2011;52:1030-40.
10 Salazar J, Altés A, del Río E, Estella J, Rives S, Tasso M, et al. Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia. Pharmacogenomics J 2012;12:379-85.
11 Haase R, Elsner K, Merkel N, Stiefel M, Mauz-Körholz C, Kramm CM, et al. High dose methotrexate treatment in childhood ALL: Pilot study on the impact of the MTHFR 677C>T and 1298A>C polymorphisms on MTX-related toxicity. Klin Padiatr 2012;224:156-9.
12 D'Angelo V, Ramaglia M, Iannotta A, Francese M, Pota E, Affinita MC, et al. Influence of methylenetetrahydrofolate reductase gene polymorphisms on the outcome of pediatric patients with non-Hodgkin lymphoma treated with high-dose methotrexate. Leuk Lymphoma 2013;54: 2639-44.
13 Zheng MM, Yue LJ, Chen XW, Wen FQ, Li CG, Yang CL, et al. Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia. Zhongguo Dang Dai Er Ke Za Zhi 2013;15:201-6.
14 Liao QC, Li XL, Liu ST, Zhang Y, Li TY, Qiu JC. Association between the methylenetetrahydrofolate reductase gene polymorphisms and haplotype with toxicity response of high dose methotrexate chemotherapy. Zhonghua Liu Xing Bing Xue Za Zhi 2012;33:735-9.