Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation

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Kim, Inho; Lee, Kyung-Hun; Kim, Jin Hee; Ra, Eun Kyung; Yoon, Sung-Soo; Hong, Yun-Chul; Park, Sung Sup; Kim, Chul Soo; Park, Seonyang; Kim, Byoung Kook
Issue Date
Springer Verlag
Ann Hematol 86:41-48
AdolescentAdultCase-Control StudiesFemaleGene FrequencyGenotype*Hematopoietic Stem Cell Transplantation/adverse effects/mortality*Histocompatibility TestingHumansMaleMethylenetetrahydrofolate Reductase (NADPH2)/*geneticsMiddle Aged*Polymorphism, Single Nucleotide*SiblingsSurvival AnalysisTransplantation, Homologous/adverse effects/mortalityTreatment Outcome
To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a short course of MTX as a graft-versus-host disease prophylaxis. Patients with the 677TT genotype showed higher total bilirubin levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07) and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6 vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/mul was slower for patients with the 677TT genotype than for patients with other genotypes (677TT, 59 days; 677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T polymorphism on treatment-related mortality (TRM) were also analyzed. One-year cumulative TRMs for patients with the TT genotype and the other genotypes were 66 and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56% (p=0.11). No association was observed between the A1298C polymorphism and clinical outcome for any of the different genotypes. Therefore, patients at high risk of developing hepatic toxicity and with a poor likelihood of survival could be selected by genotyping MTHFR C677T before allogeneic stem cell transplantation.
1432-0584 (Electronic)
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College of Medicine/School of Medicine (의과대학/대학원)Laboratory Medicine (검사의학전공)Journal Papers (저널논문_검사의학전공)
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