Abstract
In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.
Highlights
Therapy-related myelodysplastic syndromes (t-MDS) are defined as MDS occurring as a complication of cytotoxicFrom the beginning, t-MDS patients were placed together into the large group of therapy-related myeloid neoplasms (t-MNs), independent of blast count and morphologic features such as cellularity or dysplasia
Patients with high-risk (22%) and very high-risk (31%) IPSS-R score were more frequent among t-MDS than in the primary MDS (p-MDS) group
Patient characteristics as well as a comparison to p-MDS can be found in Table 1 and Supplementary Table 1
Summary
Therapy-related myelodysplastic syndromes (t-MDS) are defined as MDS occurring as a complication of cytotoxicFrom the beginning, t-MDS patients were placed together into the large group of therapy-related myeloid neoplasms (t-MNs), independent of blast count and morphologic features such as cellularity or dysplasia. The 2016 WHO-classification recognizes the fact that t-MNs can be sub-classified morphologically into t-MDS, t-MDS/MPN, and t-AML, but considers it best to distinguish them collectively from p-MNs as “a unique clinical syndrome” [1, 2], insinuating again that all t-MDS have a uniformly poor prognosis. If this were considered true, all treatable patients would need to receive a recommendation for an intensive/disease-modifying treatment approach, including allogeneic transplantation, chemotherapy, or hypomethylating agents. Not categorizing t-MDS as a subgroup of MDS limits proper clinical decision-making, interferes with epidemiological/ biological research, and supports the established practice of excluding t-MDS from clinical studies [24], thereby potentially preventing therapeutic improvements
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