Myelodysplastic Syndromes: Recent Advancements in Risk Stratification and Unmet Therapeutic Challenges

Articles MDS published on April 21, 2014

Bejar R, et al. Myelodysplastic Syndromes: Recent Advancements in Risk Stratification and Unmet Therapeutic Challenges. 2013 ASCO Educational Book.

This chapter in the 2013 ASCO Educational Book by Bejar, et al., addresses several key questions in the management of myelodysplastic syndrome (MDS). The first is how to better classify and risk-stratify MDS and tailor treatment accordingly by using new models of clinical and molecular risk stratification; these include the revised International Prognostic Scoring System (IPSS-R), the MD Anderson Lower-Risk Prognostic Scoring System (LR-PSS), and the MD Anderson Comprehensive Scoring System (MDA-CSS). Some models contain more cytogenetic risk groups and more chromosomal abnormalities, some give more weight to cytopenias, and some can be applied to previously treated patients and patients with chronic myelomonocytic leukemia. In addition, the article addresses the emergence of molecular markers of prognosis, such as the 40 recurrently mutated genes that have been identified in MDS patients. Future models will be incorporating mutational information into existing prognostic systems, which will no doubt lend accuracy, however, the authors caution that there are potential challenges to the clinical use of molecular genetics in MDS.

This article also addresses the diagnosis and management of the challenging group of patients with an overlap of MDS and myeloproliferative neoplasms (MPN), ie, MDS/MPN, which has its own distinct disease biology and outcomes. This group includes chronic myelomonocytic leukemia and MDS/MPN-u provisional entity RARS-T. It is becoming appreciated that unique diagnostic and treatment approaches need to be tailored to MDS/MPN, and likely to their individual subtypes. Criteria for diagnosis, descriptions of cytogenetics and recommendations for treatment are included.

Finally, the article reports the most recent findings for various combinations of currently used agents and previews the pipeline of novel compounds. These include P38-MAPK inhibitors, transforming growth factor-beta inhibitors, indoleamine 2,3-dioxygenase inhibitors, mouse double minute 2 homolog (MDM2)-p53 pathway modulators, thrombopoietin-stimulating agents (TPO) stimulants, tyrosine kinase inhibitors, aminopeptidase inhibitors, and hedgehog inhibitors.

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Last modified: April 21, 2014