The influence of SLC19A1 gene polymorphisms on high dose methotrexate toxicity in childhood acute lymphoblastic leukemia and non-Hodgkin malignant lymphoma: introducing a haplotype based approach
Background: We investigated the clinical relevance of SLC19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML).
Mehods: Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities.
Results: Patients with SLC19A1 rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071-0.725), p<0.009). SLC19A1 TGTTCCG haplotype (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023-0.852), p=0.030).
Discussion: SLC19A1 SNP and haplotype analysis could provide additional information for personalised HD-MTX therapy in children with ALL/NHML in order to achieve safer treatment. However further studies are needed to validate the results.