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The effect of folinic acid on methylenetetrahydrofolate reductase polymorphisms in methotrexate-treated allogeneic hematopoietic stem cell transplants.

Abstract
This study examined the contribution single nucleotide polymorphisms (SNPs) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have on clinical outcomes in hematopoietic stem cell transplant patients treated with the antiproliferative drug methotrexate. Two common SNPs, 677C>T and 1298A>C, were genotyped by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) from samples obtained from patient DNA samples. Eleven clinical outcomes including survival and graft-versus-host disease (GVHD) were assessed against donor and recipient MTHFR genotypes against pretransplantation variables. Folinic acid (FA) as treatment for oral mucositis toxicity was used at investigator discretion in 72 of 140. Donor MTHFR 1298AA genotype was associated with decreased 5-year survival (P = .03) and event-free survival (EFS) (P = .02) in patients withheld FA. Donor MTHFR 677CC genotype was associated with earlier GVHD (P = .003), and more severe acute GVHD (P = 0.02). FA was significantly associated with decreased survival (P = 0.02) in patients given a donor MTHFR 677CT transplant. FA was significantly associated with decreased survival (P = .04), EFS (P = .009) in patients given a donor MTHFR 1298AC transplant MTHFR gene polymorphisms indicate a potentially useful gene for donor selection where more than one donor is available. Use of FA following transplantation should be reconsidered in the context of patient and donor MTHFR genotypes.
AuthorsNicholas M Murphy, Mary Diviney, Jeff Szer, Peter Bardy, Andrew Grigg, Rosemary Hoyt, Belinda King-Kallimanis, Rhonda Holdsworth, James McCluskey, Brian D Tait
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 18 Issue 5 Pg. 722-30 (May 2012) ISSN: 1523-6536 [Electronic] United States
PMID21920473 (Publication Type: Journal Article, Multicenter Study)
CopyrightCopyright © 2012 American Society for Blood and Marrow Transplantation. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Leucovorin
  • Methotrexate
Topics
  • Antineoplastic Agents (administration & dosage, adverse effects)
  • Australia
  • Cohort Studies
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Female
  • Genotype
  • Graft vs Host Disease (prevention & control)
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leucovorin (administration & dosage, therapeutic use)
  • Male
  • Methotrexate (administration & dosage, adverse effects)
  • Methylenetetrahydrofolate Reductase (NADPH2) (genetics, metabolism)
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide (genetics)
  • Severity of Illness Index
  • Stomatitis (drug therapy, enzymology, genetics, mortality)
  • Transplantation, Homologous

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