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

Myelodysplastic syndromes (MDS) have varied prognoses and require a risk-adapted treatment strategy for treatment optimization. Recently, a molecular prognostic model (Molecular International Prognostic Scoring System [IPSS-M]) that combines clinical parameters, cytogenetic abnormalities, and mutation topography was proposed. This study validated the IPSS-M in 649 patients with primary MDS (based on the 2022 International Consensus Classification [ICC]) and compared its prognostic power to those of the IPSS and revised IPSS (IPSS-R). Overall, 42.5% of the patients were reclassified and 29.3% were up-staged from the IPSS-R. After the reclassification, 16.9% of the patients may receive different treatment strategies. The IPSS-M had greater discriminative potential than the IPSS-R and IPSS. Patients with high, or very high-risk IPSS-M might benefit from allogeneic hematopoietic stem cell transplantation. IPSS-M, age, ferritin level, and the 2022 ICC categorization predicted outcomes independently. After analyzing demographic and genetic features, complementary genetic analyses, including KMT2A-PTD, were suggested for accurate IPSS-M categorization of patients with ASXL1, TET2, STAG2, RUNX1, SF3B1, SRSF2, DNMT3A, U2AF1, and BCOR mutations and those classified as MDS, not otherwise specified with single lineage dysplasia/multi-lineage dysplasia based on the 2022 ICC. This study confirmed that the IPSS-M can better risk-stratified MDS patients for optimized therapeutic decision-making.

Validation of the prognostic significance of the 2022 European LeukemiaNet risk stratification system in intensive chemotherapy treated aged 18 to 65 years patients with de novo acute myeloid leukemia.

The European LeukemiaNet (ELN) recently proposed a revised recommendation for the diagnosis and management of acute myeloid leukemia (AML) in adults, recognized as ELN-2022. However, validation in a large real-world cohort remains lacking. In this study, we aimed to validate the prognostic relevance of the ELN-2022 in a cohort of 809 de novo, non-M3, younger (ages 18-65 years) AML patients receiving standard chemotherapy. The risk categories of 106 (13.1%) patients were reclassified from that determined using ELN-2017 to that determined using ELN-2022. The ELN-2022 effectively helped distinguish patients as favorable, intermediate, and adverse risk groups in terms of remission rates and survival. Among patients who achieved first complete remission (CR1), allogeneic transplantation was beneficial for those in the intermediate risk group, but not for those in the favorable or adverse risk groups. We further refined the ELN-2022 system by re-categorizing AML patients with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 with KIThigh , JAK2 or FLT3-ITDhigh mutations into the intermediate risk subset, AML patients with t(7;11)(p15;p15)/NUP98::HOXA9 and AML patients with co-mutated DNMT3A and FLT3-ITD into the adverse risk subsets, and AML patients with complex or monosomal karyotypes, inv (3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2,MECOM(EVI1) or TP53 mutation into the very adverse risk subset. The refined ELN-2022 system performed effectively to distinguish patients as favorable, intermediate, adverse, and very adverse risk groups. In conclusion, the ELN-2022 helped distinguish younger, intensively treated patients into three groups with distinct outcomes; the proposed refinement of ELN-2022 may further improve risk stratification among AML patients. Prospective validation of the new predictive model is necessary.