Perspectives on Myelodysplastic Neoplasm Diagnosis: A Comparative Analysis of the Latest World Health Organization Classifications and the International Concensus Classification

Introduction : Myelodysplastic neoplasm (MDS) is a category of clonal hematopoietic stem cell neoplasms, defined by cytopenias and morphologic dysplasia, characterized by progressively ineffective hematopoiesis and increased risk of acute myeloid leukemia (AML). The 5th edition of the World Health Organization (WHO 2022) classification grouped MDS entities into two families: those having defining genetic abnormalities and those that are morphologically defined. The former newly included biallelic TP53 inactivation (MDS-biTP53) and SF3B1 mutation, meanwhile the latter newly included hypoplastic MDS (h-MDS) and MDS with fibrosis (MDS-F). An independent proposal, the International Consensus Classification (ICC), was also published during the same period. This study aims to compare and analyze these two classifications, focusing on MDS’s diagnostic criteria and entity definition. Herein, we describe the redistribution of the MDS according to the WHO 2022 classification and ICC and evaluated their significance in predicting patient’s outcomes.

Methods : This study included a total of 639 patients who were diagnosed with MDS based on the 4th edition of WHO classification in Seoul St. Mary’s hospital from 2016 to 2022. As part of the study, all patients were reclassified using the updated WHO 2022 classification and ICC through a comprehensive review of bone marrow aspiration and biopsy, as well as the results of whole genetic studies, including cytogenetic analysis, fluorescence in situ hybridization, and targeted panel next-generation sequencing. Risk stratification was determined by using the International Prognostic Scoring System for MDS (IPSS-R, WPSS and IPSS-M).

Results : Among the 639 patients, six were classified as 'clonal cytopenia of undetermined significance' by WHO 2022 and ICC. In the WHO 2022 classification, 22 patients were categorized as AML, whereas ICC only identified nine of them due to low blast count (<10%). Out of the newly defined MDS patients (n=611), 12.6% (n=77) were genetically defined MDS, and 87.4% (n=534) were morphologically defined MDS. Regarding the WHO 2022 categories, MDS-biTP53 and MDS-SF3B1 accounted for 5.4% (n=33) and 6.3% (n=39) of cases, respectively, whereas h-MDS and MDS-F accounted for 11.9% (n=73) and 1.8% (n=11), respectively. As for the ICC, MDS, not otherwise specified (NOS) accounted for 327 patients with 77 having single lineage dysplasia and 250 having multilineage dysplasia. The h-MDS was also included in these criteria. Of 33 MDS-biTP53 cased identified by the WHO 2022 classification, 25 were categorized as MDS-TP53 and 8 as MDS/AML-TP53 in the ICC, which included an additional four patients. Moreover, 72 patients were classified as MDS/AML by ICC, with 35 of them presenting genetic mutations and 9 exhibiting cytogenetic abnormalities. The median survival of the 611 patients were 86 months (95% confidence interval (CI): 65-111). The WHO 2022 classification demonstrated significant prognostic discrimination based on diagnosis subtype (P <0.001). MDS-biTP53 exhibited the worst outcome [hazard ratio (HR): 7.24, 95% CI: 2.87 to 18.22], followed by MDS-F (HR: 5.64, 95% CI: 1.44 to 22.08) and MDS-IB2 (HR: 2.76, 95% CI: 1.72 to 4.42), in comparison to MDS-LB. On the other hand, the ICC did not reveal significant prognostic significance. The distribution of IPSS-R, WPSS and IPSS-M was similar and also showed meaningful prognostic discrimination (P <0.001).

Conclusions : The results validated the clinical relevance of updated WHO 2022 classification for MDS and indicated that the newly defined categories such as MDS-biTP53 and MDS-F are unique disease types evidenced by their particular prognostic significance.