Diagnosis and Treatment of Myelodysplastic Syndrome

Diagnostic Classification

The World Health Organization (WHO) criteria for myelodysplastic syndrome (MDS) require ≥10% dysplasia in one or more myeloid lineages, which is met by the presence of dysplastic erythroblasts with suppressed erythropoiesis 3, 1, 4
A bone marrow blast percentage of 1% places this case in the lower blast count category, likely refractory cytopenia with multilineage dysplasia (RCMD) or potentially refractory anemia with excess blasts-1 (RAEB-1) if blasts are between 5-9% on repeat assessment 3, 1
The presence of increased plasma cells on biopsy without M-protein or paraprotein excludes plasma cell dyscrasia but warrants monitoring, as this can occasionally accompany MDS 4, 2
A normal karyotype is prognostically intermediate in the IPSS-R scoring system 1, 2
Elevated endogenous erythropoietin (EPO) levels >750 U/L indicate a poor response to erythropoiesis-stimulating agents (ESAs) 4, 2, 5

The International Prognostic Scoring System-Revised (IPSS-R) score must be calculated to determine the treatment approach, considering factors such as bone marrow blast percentage, cytogenetics, and hemoglobin, platelet, and absolute neutrophil count values 1, 2
For lower-risk MDS, the European Society for Medical Oncology (ESMO) recommends ESAs as first-line therapy for symptomatic anemia, with expected response rates of ~60% when baseline EPO is low and transfusion requirement is limited 5, 6
However, elevated EPO levels >500 U/L predict a poor response to ESA therapy, and alternative treatments such as antithymocyte globulin (ATG) with or without cyclosporine, lenalidomide, or azacitidine may be considered 4, 2, 5
For higher-risk MDS, the National Comprehensive Cancer Network (NCCN) recommends hypomethylating agents such as azacitidine as first-line therapy, with a standard regimen of 75 mg/m² subcutaneously daily for 7 consecutive days every 28 days 8
Allogeneic stem cell transplantation (SCT) should be considered in younger, fit patients with higher-risk disease, as it represents the only curative option 3, 1

Complete IPSS-R scoring with current hemoglobin, platelet count, and absolute neutrophil count values to determine the treatment approach 1, 2
Assess transfusion requirements, as this impacts treatment selection 5, 6
Consider HLA-DR15 typing if immunosuppressive therapy is being considered, and evaluate for PNH clone by flow cytometry as small PNH clones can accompany MDS and influence treatment decisions 9, 7, 1, 2
Perform molecular testing by next-generation sequencing to detect clonal mutations, which provide prognostic information and may guide therapy 1, 2