AIM: Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma. PATIENTS & METHODS: Patients (n = 71) were genotyped for MTHFR C677T, MTHFR A1298C, SLC19A1 G80A, ABCG2 C421A and ABCB1 C3435T using the Sequenom MassARRAY platform. Plasma MTX concentrations at 48 h were measured by fluorescence polarization immunoassay. RESULTS: Forty-eight patients had hematopoietic toxicity, 51 had hepatic toxicity and 36 had mucositis. Patients homozygous for MTHFR 677TT were associated with increased risk of both hematopoietic (odds ratio [OR]: 9.03; 95% CI: 2.28-36.16; p = 0.002) and hepatic (OR: 3.92; 95% CI: 1.01-15.11; p = 0.036) toxicities. Hepatic toxicity was associated with SLC19A1 G80A (OR: 5.27, 95% CI: 1.21-22.72; p = 0.032) and ABCB1 C3435T (OR: 8.62; 95% CI: 1.96-37.57; p = 0.004). However, polymorphisms in MTHFR A1298C and ABCG2 C421A were not associated with any of the toxicities, and mucositis was not associated with any polymorphisms of the MTX pathway genes. Patients with MTHFR C677T and ABCB1 C3435T polymorphisms appear to have significantly higher MTX plasma concentrations (p < 0.05). CONCLUSION: Our results in Asian adults provides evidence for the contribution pharmacogenetics to the toxicity of high-dose MTX and plasma MTX concentrations at 48 h following treatment in patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma. These results will contribute towards the effort of MTX therapy individualization.
AIM: Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma. PATIENTS & METHODS:Patients (n = 71) were genotyped for MTHFRC677T, MTHFRA1298C, SLC19A1G80A, ABCG2 C421A and ABCB1C3435T using the Sequenom MassARRAY platform. Plasma MTX concentrations at 48 h were measured by fluorescence polarization immunoassay. RESULTS: Forty-eight patients had hematopoietic toxicity, 51 had hepatic toxicity and 36 had mucositis. Patients homozygous for MTHFR 677TT were associated with increased risk of both hematopoietic (odds ratio [OR]: 9.03; 95% CI: 2.28-36.16; p = 0.002) and hepatic (OR: 3.92; 95% CI: 1.01-15.11; p = 0.036) toxicities. Hepatic toxicity was associated with SLC19A1G80A (OR: 5.27, 95% CI: 1.21-22.72; p = 0.032) and ABCB1C3435T (OR: 8.62; 95% CI: 1.96-37.57; p = 0.004). However, polymorphisms in MTHFRA1298C and ABCG2 C421A were not associated with any of the toxicities, and mucositis was not associated with any polymorphisms of the MTX pathway genes. Patients with MTHFRC677T and ABCB1C3435T polymorphisms appear to have significantly higher MTX plasma concentrations (p < 0.05). CONCLUSION: Our results in Asian adults provides evidence for the contribution pharmacogenetics to the toxicity of high-dose MTX and plasma MTX concentrations at 48 h following treatment in patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma. These results will contribute towards the effort of MTX therapy individualization.
Authors: Ankit Anand; Prathima Anandi; Natasha A Jain; Kit Lu; Neil Dunavin; Christopher S Hourigan; Robert Q Le; Puja D Chokshi; Sawa Ito; David F Stroncek; Marianna Sabatino; A John Barrett; Minoo Battiwalla Journal: Support Care Cancer Date: 2015-07-21 Impact factor: 3.603
Authors: Ravi Ramalingam; Harpreet Kaur; Julius Xavier Scott; Latha M Sneha; Ganeshprasad Arunkumar; Arathi Srinivasan; Solomon F D Paul Journal: Cancer Chemother Pharmacol Date: 2022-02-14 Impact factor: 3.333
Authors: Mark C Zobeck; M Brooke Bernhardt; Kala Y Kamdar; Karen R Rabin; Philip J Lupo; Michael E Scheurer Journal: Pediatr Blood Cancer Date: 2021-03-31 Impact factor: 3.167