Comparison of the revised 4th (2016) and 5th (2022) editions of the World Health Organization classification of myelodysplastic neoplasms

Abstract

We used data from 852 consecutive subjects with myelodysplastic neoplasms (MDS) diagnosed according to the 2016 (revised 4th) World Health Organization (WHO) criteria to evaluate the 2022 (5th) edition WHO classification of MDS. 30 subjects previously classified as MDS with an NPM1 mutation were re-classified as acute myeloid leukaemia (AML). 9 subjects previously classified as MDS-U were re-classified to clonal cytopenia of undetermined significance (CCUS). The remaining 813 subjects were diagnosed as: MDS-5q (N = 11 [1%]), MDS-SF3B1 (N = 70 [9%]), MDS-biTP53 (N = 53 [7%]), MDS-LB (N = 293 [36%]), MDS-h (N = 80 [10%]), MDS-IB1 (N = 161 [20%]), MDS-IB2 (N = 103 [13%]) and MDS-f (N = 42 [5%]) and MDS-biTP53 (N = 53 [7%]). 34 of these subjects came from the 53 (64%) MDS-biTP53 previously diagnosed as MDS-EB. Median survival of subjects classified as MDS using the WHO 2022 criteria was 45 months (95% Confidence Interval [CI], 34, 56 months). Subjects re-classified as MDS-biTP53 and MDS-f had significantly briefer median survivals compared with other MDS sub-types (10 months, [8, 12 months] and 15 months [8, 23 months]). In conclusion, our analyses support the refinements made in the WHO 2022 proposal.

Fig. 1. Summary of the relationship between MDS patients’ subtypes defined in the WHO 2016 and WHO 2022 classification.

WHO World Health Organization, MDS myelodysplastic syndromes(neoplasms), MDS-U MDS unclassifiable, SLD single lineage dysplasia, MLD multilineage dysplasia, RS-SLD ring sideroblasts with SLD, RS-MLD ring sideroblasts with MLD, EB1/2 excess blasts type 1/2, 5q- isolated 5q deletion, biTP53 biallelic TP53 inactivation, LB low blasts, MDS-SF3B1 MDS with low blasts and SF3B1 mutation, MDS-h MDS, hypoplastic, IB1/2 increased blasts type1/2, MDS-f MDS with fibrosis.

Fig. 2. The frequency of 33 significant mutated genes (>1%) in MDS patients according to the WHO 2022 classification.

WHO World Health Organization, MDS myelodysplastic syndromes(neoplasms), 5q- isolated 5q deletion, biTP53 biallelic TP53 inactivation, LB low blasts, MDS-SF3B1 MDS with low blasts and SF3B1 mutation, MDS-h MDS hypoplastic, IB1/2 increased blasts type1/2, MDS-f MDS with fibrosis.

Fig. 3. Classification and prognostication of MDS patients.

Overall survival of MDS patients stratified according to the IPSS-R and IPSS-M (A) Repartition of IPSS-R/IPSS-M risk categories and WHO 2022 sub-types (B). WHO, World Health Organization, MDS myelodysplastic syndromes(neoplasms), 5q- isolated 5q deletion, biTP53 biallelic TP53 inactivation, LB low blasts, MDS-SF3B1 MDS with low blasts and SF3B1 mutation, MDS-h MDS hypoplastic, IB1/2 increased blasts type1/2, MDS-f MDS with fibrosis, IPSS-R Revised International Prognostic Scoring System, IPSS-M International Prognostic Scoring Systems-Molecular.

Fig. 4. Kaplan–Meier survival curves for overall survival in MDS patients.

Survival according to the WHO 2022 classification for MDS (A). Survival according to the WHO 2016 classification for MDS (B). WHO, World Health Organization, MDS myelodysplastic syndromes(neoplasms), MDS-U MDS unclassifiable, SLD single lineage dysplasia, MLD multilineage dysplasia, RS-SLD ring sideroblasts with SLD, RS-MLD ring sideroblasts with MLD, EB1/2 excess blasts type 1/2, 5q- isolated 5q deletion, biTP53 biallelic TP53 inactivation, LB low blasts, MDS-h MDS hypoplastic, IB1/2 increased blasts type1/2, MDS-f MDS with fibrosis, OS overall survival.