Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes Journal Article


Authors: Bejar, R.; Stevenson, K. E.; Caughey, B. A.; Abdel-Wahab, O.; Steensma, D. P.; Galili, N.; Raza, A.; Kantarjian, H.; Levine, R. L.; Neuberg, D.; Garcia-Manero, G.; Ebert, B. L.
Article Title: Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes
Abstract: Purpose: A subset of patients with myelodysplastic syndromes (MDS) who are predicted to have lower-risk disease as defined by the International Prognostic Scoring System (IPSS) demonstrate more aggressive disease and shorter overall survival than expected. The identification of patients with greater-than- predicted prognostic risk could influence the selection of therapy and improve the care of patients with lower-risk MDS. Patients and Methods: We performed an independent validation of the MD Anderson Lower-Risk Prognostic Scoring System (LR-PSS) in a cohort of 288 patients with low- or intermediate-1 IPSS risk MDS and examined bone marrow samples from these patients for mutations in 22 genes, including SF3B1, SRSF2, U2AF1, and DNMT3A. Results: The LR-PSS successfully stratified patients with lower-risk MDS into three risk categories with significant differences in overall survival (20% in category 1 with median of 5.19 years [95% CI, 3.01 to 10.34 years], 56% in category 2 with median of 2.65 years [95% CI, 2.18 to 3.30 years], and 25% in category 3 with median of 1.11 years [95% CI, 0.82 to 1.51 years]), thus validating this prognostic model. Mutations were identified in 71% of all samples, and mutations associated with a poor prognosis were enriched in the highest-risk LR-PSS category. Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS. Only EZH2 mutations retained prognostic significance in a multivariable model that included LR-PSS and other mutations (hazard ratio, 2.90; 95% CI, 1.85 to 4.52). Conclusion: Combining the LR-PSS and EZH2 mutation status identifies 29% of patients with lower-risk MDS with a worse-than-expected prognosis. These patients may benefit from earlier initiation of disease-modifying therapy. © 2012 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; middle aged; survival analysis; unclassified drug; gene mutation; major clinical study; overall survival; mutation; cancer risk; validation process; follow-up studies; reproducibility of results; bone marrow; hemoglobin; protein p53; risk assessment; myelodysplastic syndrome; nucleotide sequence; scoring system; predictive value of tests; thrombocyte count; dna sequence; multivariate analysis; dna mutational analysis; myelodysplastic syndromes; transcription factor runx1; dna methyltransferase 3a; transcription factor ezh2; named inventories, questionnaires and rating scales; cancer prognosis; polycomb repressive complex 2; asxl1 protein; sf3b1 protein; srsf2 protein; u2af1 protein; lower risk prognostic scoring system
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 27
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-09-20
Start Page: 3376
End Page: 3382
Language: English
DOI: 10.1200/jco.2011.40.7379
PROVIDER: scopus
PMCID: PMC3438234
PUBMED: 22869879
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: JCOND" - "Molecular Sequence Numbers: GENBANK: NM_003016, NM_012433, NM_175629;" - "Source: Scopus"
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MSK Authors
  1. Ross Levine
    469 Levine