Myelodysplastic syndromes: toward a risk-adapted treatment approach

Abstract

Several classification and scoring systems have been developed in myelodysplastic syndromes (MDS to predict the risk of progression to acute myeloid leukemia and survival. These prognostication models have been also used to inform therapeutic decision-making in a risk-adapted fashion. Patient-related factors such as age, comorbidities, and functional status have to be considered as well. Here we review a risk-guided therapeutic approach for the management of MDS patients. It is anticipated that the improved understanding of the complex pathogenesis of MDS and the recent discovery of important molecular lesions will be translated into novel therapeutic approaches. Additionally, some prognostic aberrations are expected to be incorporated into the prognostic tools with the goal of improving their prognostic precision and therefore allow for a more informed therapeutic decision-making based on the individual’s risk profile.

Keywords::

• azacitidine
• decitabine
• hematopoietic growth factors
• hematopoietic stem cell transplant
• hypomethylating agents
• lenalidomide
• myelodysplastic syndromes

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • MDS include a heterogeneous group of clonal hematopoietic stem cell disorders characterized by dysplasia, ineffective hematopoiesis and a variable risk of leukemic progression.

• • Several scoring systems for risk stratification of MDS have been developed. The IPSS scoring system is the most widely used system and has been revised recently (IPSS-R) to improve prognostic precision.

• • A risk-adapted treatment approach to MDS is the recommended strategy to select the appropriate therapy.

• • Patient-related factors such as age, comorbidities and patient’s preference should be considered in addition to disease-specific factors in the clinical decision-making process.

• • Treatment options for Low and Intermediate-1 MDS according to IPSS: ESAs, ISAs are appropriate options. Lenalidomide is the treatment of choice in patients who have with del5q. Hypomethylating agents are reasonable options for low-risk MDS patients who do not respond to therapy with ESA, lenalidomide or ISA. HSCT can be offered to selected patients with low and intermediate-1 risk MDS patients who develop evidence of disease progression on other therapies.

• • Treatment options for Intermediate-2 and high-risk MDS include hypomethylating agents. HSCT should be considered early for patients in this category.