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Mayo Alliance Prognostic Model for Myelodysplastic Syndromes: Integration of Genetic and Clinical Information

      Abstract

      Objective

      To develop a new risk model for primary myelodysplastic syndromes (MDS) that integrates information on mutations, karyotype, and clinical variables.

      Patients and Methods

      Patients with World Health Organization–defined primary MDS seen at Mayo Clinic (MC) from December 28, 1994, through December 19, 2017, constituted the core study group. The National Taiwan University Hospital (NTUH) provided the validation cohort. Model performance, compared with the revised International Prognostic Scoring System, was assessed by Akaike information criterion and area under the curve estimates.

      Results

      The study group consisted of 685 molecularly annotated patients from MC (357) and NTUH (328). Multivariate analysis of the MC cohort identified monosomal karyotype (hazard ratio [HR], 5.2; 95% CI, 3.1-8.6), “non-MK abnormalities other than single/double del(5q)” (HR, 1.8; 95% CI, 1.3-2.6), RUNX1 (HR, 2.0; 95% CI, 1.2-3.1) and ASXL1 (HR, 1.7; 95% CI, 1.2-2.3) mutations, absence of SF3B1 mutations (HR, 1.6; 95% CI, 1.1-2.4), age greater than 70 years (HR, 2.2; 95% CI, 1.6-3.1), hemoglobin level less than 8 g/dL in women or less than 9 g/dL in men (HR, 2.3; 95% CI, 1.7-3.1), platelet count less than 75 × 109/L (HR, 1.5; 95% CI, 1.1-2.1), and 10% or more bone marrow blasts (HR, 1.7; 95% CI, 1.1-2.8) as predictors of inferior overall survival. Based on HR-weighted risk scores, a 4-tiered Mayo alliance prognostic model for MDS was devised: low (89 patients), intermediate-1 (104), intermediate-2 (95), and high (69); respective median survivals (5-year overall survival rates) were 85 (73%), 42 (34%), 22 (7%), and 9 months (0%). The Mayo alliance model was subsequently validated by using the external NTUH cohort and, compared with the revised International Prognostic Scoring System, displayed favorable Akaike information criterion (1865 vs 1943) and area under the curve (0.87 vs 0.76) values.

      Conclusion

      We propose a simple and contemporary risk model for MDS that is based on a limited set of genetic and clinical variables.

      Abbreviations and Acronyms:

      AIC (Akaike information criterion), AML (acute myeloid leukemia), AUC (area under the curve), BM (bone marrow), GVHD (graft-vs-host disease), HCT (allogeneic hematopoietic stem cell transplant), HR (hazard ratio), IPSS-R (revised International Prognostic Scoring System), MC (Mayo Clinic), MDS (myelodysplastic syndrome), MK (monosomal karyotype), NTUH (National Taiwan University Hospital), ROC (receiver operating characteristic)
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      Linked Article

      • Improving Prognostic Tools for Patients With Myelodysplastic Syndromes
        Mayo Clinic ProceedingsVol. 93Issue 10
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          Myelodysplastic syndromes (MDS) is a term used to refer to a very complex group of myeloid stem cell disorders.1 It most frequently affects older individuals and those previously treated with chemotherapy and/or radiation therapy. Several genetic predisposition syndromes that can affect younger individuals have also been described. In general, most patients present with cytopenia that will trigger a diagnostic procedure. Today, this process should include evaluation of the morphology of the cellular elements in the bone marrow, a cytogenetic analysis, and targeted next-generation sequencing.
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