Validation of the 5th Edition of the World Health Organization Classification of Myelodysplastic Neoplasms on 852 Consecutive De Novo Patients from a Single Institute

Abstract

Background: A summary of the World Health Organization (WHO) 5th edition (2022) classification of myelodysplastic neoplasms (MDS) has been published recently. As compared to the 2016 (revised 4th) WHO criteria, the newest proposal places greater emphasis on genomic and pathology features. In this study, we assess the validity of the WHO 2022 classification for MDS patients. Methods: Data from 852 consecutive subjects ≥ 18 years with newly-diagnosed MDS according to the WHO 2016 criteria in our center from August 30, 2016 to September 22, 2021 were interrogated. Subjects were re-diagnosed and re-classified according to WHO 2022 guidelines. The last follow-up was on June 4, 2022, with a median follow-up of 24 months. Results: Applying the WHO 2022 guidelines, 30 subjects with an NPM1 mutation were re-classified as acute myeloid leukemia (AML) who were previously classified as MDS with excess blast type2 (MDS-EB2; n = 13), MDS with multi-lineage dysplasia (MDS-MLD; n = 9), MDS with excess blast type1 (MDS-EB1; n = 6) and MDS unclassifiable (MDS-U; n = 2) according to WHO 2016 criteria. Nine subjects previously classified as (MDS-U) were re-classified to clonal cytopenia of undetermined significance (CCUS). Re-classification of remaining 813 subjects between the WHO 2016 to WHO 2022 classification are displayed in Figure1. Classification of the 11 subjects with MDS with low blasts and isolated del(5q) (MDS-5q) remained unchanged. In addition to prior MDS with ring sideroblasts (MDS-RS) patients (n=45), 25 subjects were reclassified as MDS with low blasts and SF3B1 mutation (MDS-SF3B1) because the new criteria have no limitation on numbers of ring sideroblasts. We re-classified 53 subjects as MDS-biTP53, most commonly those with excess blasts (34/53; 64%). Amongst subjects without the genetic abnormalities defined above, 80 previously classified as MDS with singe/multi-lineage dysplasia (MDS-SLD/MLD) or MDS-U were re-classified as hypoplastic MDS (MDS-h) and the remaining 293 as MDS with low blasts (MDS-LB). Subjects previously classified as MDS-EB1 or EB2 were re-classified as MDS with increased blasts type1 (MDS-IB1; n = 161) or MDS with increased blasts type2 (MDS-IB2; n = 103) after those with MDS with fibrosis (MDS-f; n = 42) were excluded. Survival according to WHO 2022 classification for MDS are shown in Figure2. Median survival of MDS subjects was 45 months (95% Confidence Interval [CI], [34, 56] months). There were significantly briefer median survivals of subjects with MDS-biTP53 (10 months [8, 12] months) and MDS-f (15 months [8, 23 months]) compared with other subtypes. Median survivals of MDS-h and MDS-LB cohorts were unreached but those with MDS-h had longer survival (P = 0.07). Median survivals for MDS-IB1 and MDS-IB patients were 24 months ([18, 30] months) and 26 months ([17, 35] months), respectively. Survival rate between MDS-IB1 and MDS-IB2 patients were comparable (P=0.707). We next explored the prognostic value of myelofibrosis in subjects without increased blasts. 40 subjects in our cohort had grade-2/-3 myelofibrosis. 37 were re-classified from the MDS-LB cohort and 3 from the MDS-h cohort. Median survival of subjects with low blasts and myelofibrosis (MDS-LBf) was 23 months (8, 38 months), significantly briefer compared with those with MDS-LB or MDS-h (unreached; P < 0.001) comparable to subjects with MDS-IB1 (24 months; P = 0.80) or MDS-IB2 (26 months; P = 0.79) and longer compared with subjects with MDS-f (15 months; P = 0.04). We also tested the prognostic value of dysplastic lineages in subjects with MDS-LB according to WHO 2022 classification. Based on bone marrow histology 28 subjects were considered MDS-LB with single lineage dysplasia (MDS-LB-SLD) and 228, MDS-LB with multiple lineage dysplasia (MDS-LB-MLD). Median survivals of both cohorts were unreached however MDS-LB-SLD had longer survival (P = 0.01). Based on these findings, we suggest the revised WHO 2022 classification divide subjects with low blasts in to MDS-LBf, MDS-h, MDS-LB-SLD and MDS-LB-MLD. The first supersedes other categories and MDS-h overrides the diagnosis of MDS-LB-SLD or MDS-LB-MLD. Conclusion: We validate the WHO 2022 classification of MDS as thoughtful and propose some refinements to provide more accurate prognostic information. Because our study is from 1 center, external validation is needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal