1. Prognostic impact of SF3B1 mutation and multilineage dysplasia in myelodysplastic syndromes with ring sideroblasts: a Mayo Clinic study of 170 informative cases.
- Author
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Farrukh F, Abdelmagid M, Mangaonkar A, Patnaik M, Al-Kali A, Elliott MA, Begna KH, Hook CC, Hogan WJ, Pardanani A, Litzow MR, Ketterling RP, Gangat N, Arber DA, Orazi A, He R, Reichard K, and Tefferi A
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Prognosis, Aged, 80 and over, Adult, Ribonucleoprotein, U2 Small Nuclear genetics, Cell Lineage, Young Adult, RNA Splicing Factors genetics, Mutation, Phosphoproteins genetics, Anemia, Sideroblastic genetics, Anemia, Sideroblastic diagnosis, Anemia, Sideroblastic mortality, Anemia, Sideroblastic pathology, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes pathology
- Abstract
The revised 4th edition of the World Health Organization (WHO4R) classification lists myelodysplastic syndromes with ring sideroblasts (MDS-RS) as a separate entity with single lineage (MDS-RS-SLD) or multilineage (MDS-RS-MLD) dysplasia. The more recent International Consensus Classification (ICC) distinguishes between MDS with SF3B1 mutation (MDS-SF3B1) and MDS-RS without SF3B1 mutation; the latter is instead included under the category of MDS not otherwise specified. The current study includes 170 Mayo Clinic patients with WHO4R-defined MDS-RS, including MDS-RS-SLD (N=83) and MDS-RSMLD (N=87); a subset of 145 patients were also evaluable for the presence of SF3B1 and other mutations, including 126 with (87%) and 19 (13%) without SF3B1 mutation. Median overall survival for all 170 patients was 6.6 years with 5- and 10-year survival rates of 59% and 25%, respectively. A significant difference in overall survival was apparent between MDS-RS-MLD and MDS-RS-SLD (P<0.01) but not between MDS-RS with and without SF3B1 mutation (P=0.36). Multivariable analysis confirmed the independent prognostic contribution of MLD (hazard ratio=1.8, 95% confidence interval: 1.1-2.8; P=0.01) and also identified age (P<0.01), transfusion need at diagnosis (P<0.01), and abnormal karyotype (P<0.01), as additional risk factors; the impact from SF3B1 or other mutations was not significant. Leukemia-free survival was independently affected by abnormal karyotype (P<0.01), RUNX1 (P=0.02) and IDH1 (P=0.01) mutations, but not by MLD or SF3B1 mutation. Exclusion of patients not meeting ICC-criteria for MDS-SF3B1 did not change the observations on overall survival. MLD-based, as opposed to SF3B1 mutation-based, disease classification for MDS-RS might be prognostically more relevant.
- Published
- 2024
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