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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