At ASH 2021, the long-awaited Molecular International Prognostic Scoring System (IPSS-M) was presented and full publication immediately followed [
1]. In 2022 this was the topic of numerous abstracts dealing with the validation and prognostic ability of this score in real-world cohorts among others from Europe [
2] and the US [
3]. It can be concluded that the IPSS‑M improves the prognostic accuracy for progression-free survival (PFS) and overall survival (OS) when compared to the IPSS‑R (R: revised), allowing optimized therapeutic decision making. According to one study, the IPSS‑M also improved posttransplant outcome prediction (survival and prediction of relapse [
2]). The latter observation highlights that the IPSS‑M is potentially a better tool for hematopoietic stem cell transplantation (HSCT) candidate selection. In a broader context, this observation targets the following question: what to do with patients who are classified as lower-risk myelodysplastic syndrome (LR-MDS) according to the IPSS‑R but higher-risk MDS (HR-MDS) according to the IPSS‑M. In the original publication, the majority of reclassified patients were up-staged, but management of up-staged patients remains unclear [
1]. Although evidence and survival data from prospective trials are currently lacking, one may consider more intensive therapy regimens for up-staged patients, including potentially curative treatment strategies with induction therapy and consolidating HSCT. Limitations of the IPSS‑M from a global view include lack of resources and highly complex analyses.
Furthermore, as two new classifications for MDS (WHO 5th edition [
4] and ICC classification [
5]) were introduced in 2022, validations were presented and the pros and cons of each classification were critically discussed [
6]. Among many overlaps, the blast cut-off is one main difference between the two classifications and gives rise to discussion. To overcome this controversial point, Haferlach et al. presented data to exclude blast counting and categorize MDS solely based on genetic abnormalities [
7]. Nine biologically distinct disease groups with substantial differences in OS could be defined by solely considering the karyotype and molecular data. The known favorable outcome of
SF3B1 mutations and isolated
del(5q)-mutated patients together with the poor outcome of bi-allelic
TP53-mutated patients could be confirmed. In addition, complex karyotype and
RUNX1 mutation were associated with poor outcome. Within patients carrying spliceosome mutations,
RUNX1 and
ASXL1 define distinct subgroups, harboring higher progression tendency. Overall, this discussion highlights that a detailed genetic work-up is becoming more and more important, although morphologic analysis can currently not be eliminated from any diagnostic work-up of suspected MDS and MDS/AML. However, the question of the optimal blast limit still remains a point of intense discussion.