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Related Collections Transplantation Brief Reports Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2001, Vol. 98, No. 1, pp. 231-234 BRIEF REPORT Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism Cornelia M. Ulrich, Yutaka Yasui, Rainer Storb, Mark M. Schubert, John L. Wagner, Jeannette Bigler, Kiley S. Ariail, Cassie L. Keener, Sue Li, Hao Liu, Federico M. Farin, and John D. Potter From the Public Health Sciences Division and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, and School of Medicine, School of Dentistry, and School of Public Health, University of Washington, Seattle. This study investigated whether a polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T) modifies responses to methotrexate (MTX) in patients undergoing bone marrow transplantation. About 10% to 12% of the population carry the MTHFR TT genotype (enzyme activity, 30% of wild type [CC]). Patients (n = 220) with chronic myelogenous leukemia underwent marrow allografts and were given a short course of MTX. MTX toxicity measures included the oral mucositis index (OMI), speed of engraftment (platelet and granulocyte counts), and bilirubin. Patients with lower MTHFR activity (TT genotype) had 36% higher mean OMI during days 1 to 18 (+5.7, P = .046) and 20% higher OMI between days 6 and 12 (+3.8, P = .27). Platelet counts recovered more slowly among patients with the TT genotype compared to wild type (24% slower recovery to 10 000 platelets/µL, P = .23; 34% slower to 20 000/µL, P = .08). Patients with decreased MTHFR activity appear at risk of higher MTX toxicity. Because of the high prevalence of the TT genotype, these results may have implications for MTX dosage. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Attribution of posttransplantation toxicity to methotrexate regarding genotype of methylenetetrahydrofolate reductase gene (MTHFR) polymorphism needs further clarification Keitaro Matsuo, Ritsuro Suzuki, Yasuo Morishima, Nobuyuki Hamajima, Cornelia M. Ulrich, Rainer Storb, Mark M. Schubert, and John D. Potter Blood 2001 98: 2283. [Full Text] [PDF] This article has been cited by other articles: A. Ongaro, M. De Mattei, M. G. Della Porta, G. Rigolin, C. Ambrosio, F. Di Raimondo, A. Pellati, F. F. Masieri, A. Caruso, L. Catozzi, et al. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020