Clinico‐genetic and prognostic analyses of 716 patients with primary myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia based on the 2022 International Consensus Classification

Abstract

The 2022 International Consensus Classification (ICC) recategorized myeloid neoplasms based on recent advances in the understanding of the biology of hematologic malignancies, in which myelodysplastic syndrome (MDS) with blasts of 10%-19% is classified as MDS/acute myeloid leukemia (AML), MDS with mutated SF3B1, irrespective of the number of ring sideroblasts, as MDS-SF3B1, and those with multi-hit TP53 mutations as MDS with mutated TP53. In the analysis of 716 patients with MDS diagnosed according to the 2016 WHO classification, we found that 75.3% of patients remained in the MDS group based on the ICC, while 24.7% of patients were reclassified to the MDS/AML group after the exclusion of 15 patients who were classified to the AML group. Patients with MDS/AML showed a distinct mutational landscape and had poorer outcomes, compared to those with MDS. In the MDS group, patients with MDS-SF3B1 had higher frequencies of DNMT3A and TET2 mutations than those with MDS, not otherwise specified, with single lineage dysplasia or multilineage dysplasia. Patients with mutated TP53 were associated with dismal outcomes, Hsin-An Hou and Hwei-Fang Tien contributed equally to this work as joint senior authors.

Risk assessment according to IPSS-M is superior to AML ELN risk classification in MDS/AML overlap patients defined by ICC

“…S1A ). This is in line with a previous study by Lee et al analyzing 173 MDS/AML patients that additionally found OS differences between MR subgroups [ 11 ]. As expected, MDS/AML patients were mainly composed of MDS-IB2 (114/137; 83%) according to WHO 2022.…”

Validation of the molecular international prognostic scoring system in patients with myelodysplastic syndromes defined by international consensus classification

“…Patients diagnosed with MDS/AML had higher risk features than those diagnosed with MDS (Supplementary Table 3 ). Most patients with MDS or MDS/AML with mutated TP53 had very high-risk IPSS-M/R or high-risk IPSS, as described previously [ 26 ] (Supplementary Tables 4 and 5 ). Patients at higher-risk IPSS-M received disease-modifying treatments (hypomethylating agent [HMA], intensive chemotherapy, clinical trials, or HSCT) more frequently than those with lower-risk IPSS-M (46.5% vs. 17.6%, P < 0.001; Supplementary Table 2 ).…”

“…According to a recent study [ 26 ] that explored the clinico-genetic features and prognostic implication of the 2022 ICC, the MDS-del(5q), MDS- SF3B1 , and MDS, NOS with SLD/MLD were defined as low-risk MDS. In the univariable analysis, bedside IPSS-M, IPSS-R, IPSS, older age, male sex, and ferritin level were associated with poorer outcomes.…”

“…The cut-off value of variant allele frequency was 5% for diagnostic samples. Owing to the limitation of next generation sequencing (NGS), analysis of FLT3 -ITD was performed via polymerase chain reaction (PCR), followed by fluorescence capillary electrophoresis and that of KMT2A -PTD, by PCR followed by Sanger sequencing [ 25 , 26 ].…”

Comparison of the 2022 world health organization classification and international consensus classification in myelodysplastic syndromes/neoplasms

“…While SLD and MLD distinction remains in MDS, NOS subclassification in the ICC is optional in WHO-2022 criteria. Considering the heterogeneous results from previous studies [ 25 , 26 ], we believe that further analysis is warranted to assess the survival impact of the lineage of dysplasia. Our study also revealed distinct features in patients with MDS- SF3B1 compared to those with MDS-LB and RS, and MDS-LB, the latter two subtypes showing similar mutational landscapes.…”