Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS

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.

Fig. 1. Outcome of patients with t-MDS according to different tools for classification and prognosis.

a outcome according to WHO 2016, b outcome according to IPSS-R, c Outcome according to cytogenetic IPSS-R risk categories.

Fig. 2. Outcome of patients with t-MDS according WHO-classification depending on treatment in MDS phase and comparison to p-MDS.

a Outcome according to WHO-classification for treated patients. b Outcome according to WHO-classification for untreated patients. c Outcome according to WHO: p-MDS.

Fig. 3. Outcome of patients with t-MDS according WHO-classification depending on the primary disease and comparison to p-MDS.

a Outcome according to WHO: primary disease hematologic. b Outcome according to WHO: primary disease solid tumor c Outcome according to WHO: p-MDS.

Fig. 4. Distribution of risk groups according to different classification and prognostic tools for p- versus t-MDS.

a Distribution of IPSS-R subgroups in p- and t-MDS. b Distribution of WHO- subtypes (according to WPSS + RAEB-T) in p- and t-MDS. c Distribution of cytogenetic IPSS-R subgroups in p- and t-MDS. d Distribution of number of aberrations in p- and t-MDS.

Fig. 5. Distribution of risk groups according to different classification and prognostic tools for treated versus untreated patients.

a Comparison of IPSS-R risk-groups between treated and untreated patients. b Comparison of IPSS-R cytogenetic risk-groups between treated and untreated patients. c Comparison of WHO subgroups between treated and untreated patients.

Fig. 6. Comparison of outcome according to different tools for classification or prognostic evaluation t- versus p-MDS.

a Comparison p- and t-MDS according to WHO-classification. b Comparison t- and p-MDS according to IPSS-R risk-categories. c Comparison t- and p-MDS according to cytogenetic IPSS-R categories.