• Rafael Bejar, Kristen E Stevenson, Bennett Caughey, R Coleman Lindsley, Brenton G Mar, Petar Stojanov, Gad Getz, David P Steensma, Jerome Ritz, Robert Soiffer, Joseph H Antin, Edwin Alyea, Philippe Armand, Vincent Ho, John Koreth, Donna Neuberg, Corey S Cutler, and Benjamin L Ebert.
• Rafael Bejar and Bennett Caughey, University of California at San Diego, La Jolla, CA; Kristen E. Stevenson, R. Coleman Lindsley, Brenton G. Mar, David P. Steensma, Jerome Ritz, Robert Soiffer, Joseph H. Antin, Edwin Alyea, Philippe Armand, Vincent Ho, John Koreth, Donna Neuberg, and Corey S. Cutler, Dana-Farber Cancer Institute; R. Coleman Lindsley and Benjamin L. Ebert, Brigham and Women's Hospital, Harvard Medical School, Boston; Petar Stojanov, Gad Getz, and Benjamin L. Ebert, Broad Institute, Cambridge, MA.
• J. Clin. Oncol. 2014 Sep 1; 32 (25): 2691-8.

PurposeRecurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known.Patients And MethodsWe used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.ResultsMutations were identified in 92% of patients, most frequently in the ASXL1 (29%), TP53 (21%), DNMT3A (18%), and RUNX1 (16%) genes. In univariable analyses, only TP53 mutations were associated with shorter overall (OS; hazard ratio [HR], 3.74; P < .001) and progression-free survival (HR, 3.97; P < .001). After adjustment for clinical variables associated with these end points, mutations in TP53 (HR, 2.30; P = .027), TET2 (HR, 2.40; P = .033), and DNMT3A (HR, 2.08; P = .049) were associated with decreased OS. In multivariable analysis including clinical variables, complex karyotype status, and candidate genes, mutations in TP53 (HR, 4.22; P ≤ .001) and TET2 (HR, 1.68; P = .037) were each independently associated with shorter OS. Nearly one half of patients (46%) carried a mutation in TP53, DNMT3A, or TET2 and accounted for 64% of deaths. Three-year OS in patients without these mutations was 59% (95% CI, 43% to 72%), versus 19% (95% CI, 9% to 33%) in patients with these mutations.ConclusionMutations in TP53, TET2, or DNMT3A identify patients with MDS with shorter OS after HSCT.© 2014 by American Society of Clinical Oncology.

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