Myelodysplastic Syndromes: Updates and Nuances

Abstract

Myelodysplastic syndrome (MDS) is a heterogeneous, clonal stem cell disorder of the blood and marrow typically diagnosed based on the presence of persistent cytopenia(s), dysplastic cells, and genetic markers. Common issues that arise in the clinical management include difficulty confirming MDS diagnosis, lack of a standard approach with novel agents in MDS, and few prospective long-term, randomized controlled MDS clinical studies to guide allogeneic blood and marrow transplant. With the recent genetic characterization of MDS, certain aspects of these issues will be better addressed by integrating genetic data into clinical study design and clinical practice.

Keywords: Anemia; Azacitidine; Blood and marrow transplant; Myelodysplastic syndrome; Therapy-related myelodysplastic syndrome.

Figure 1. Categories of commonly mutated genes in myelodysplastic syndrome

Approximately 90% of patients with MDS will have at least one mutation in one of the genes involved in DNA methylation, RNA splicing, chromatin modification, or in the other category. The other category include genes involved in DNA damage and stress response pathway, transcriptional regulation, RAS/RAF/MEK/ERK pathway, and sister chromatid separation (cohesion complex). Each of the genes underlined are typically reported as being present in 10% or more cases of MDS.

Figure 2. How I evaluate and treat myelodysplastic syndrome

In this schematic, I summarize my general approach to patients with MDS. I provide additional details on how I choose the dose/schedule of azacitidine and monitor for response on a practical level. Many patients at the beginning of therapy (e.g., first and second cycles) will need close monitoring of their blood counts (e.g., two or three times a week) but this is usually adjusted during later cycles based on a patient’s typical length and depth of nadir. Table 1: Prediagnostic stages toward myelodysplastic syndrome.