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Validation of a Prognostic Model and the Impact of Mutations in Patients With Lower-Risk Myelodysplastic Syndromes
Open accessAbstract
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.
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International scoring system for evaluating prognosis in myelodysplastic syndromes
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Self-citationSomatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts
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Molecular Pathophysiology of Myelodysplastic Syndromes
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Metadata
- 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.
- Venue
- Journal of Clinical Oncology
- Published
- 2012-09-20
- Volume
- 30
- Issue
- 27
- Pages
- 3376-3382
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2123355582
- Cited by
- 441
- References
- 4
- FWCI
- 29.19
- Type
- journal article
- Language
- en
- Open access
- green
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