Myelodysplastic Syndromes¶

Peter Hanna

Background¶

MDS is a malignant clonal myeloid disorder resulting in ineffective (dysplastic) hematopoiesis leading to peripheral cytopenias and a risk of transformation to acute myeloid leukemia (AML)
Usually idiopathic, a disease of the elderly (median onset at age 70)
The WHO has several classification schemes for MDS
- Most important for classification is the percent of blasts in the bone marrow
- Note >20% blasts in marrow = AML. Thus MDS and AML are on a continuum

50% asymptomatic; symptoms can include nonspecific but gradual fatigue, weakness
Dysplastic cells do not work properly à infections and bleeding are more likely
Macrocytic anemia is most common finding; followed by bicytopenia or pancytopenia
Isolated neutropenia or thrombocytopenia are unusual but possible
Ask about secondary causes
- Exposure to chemicals (benzene, crude oil/gasoline industry, cigarette smoke), chemotherapy, radiation
- Medications, alcohol use, chronic infections (HIV)

Goal is to rule out reversible causes of dysplasia and cytopenias
CBC w/differential, peripheral smear, B12, folate, HIV
- Consider copper and zinc
Dysplastic changes on peripheral smear: hypogranulated/hyposegmented neutrophils, hypogranulated platelets and macrocytosis of RBCs
- Circulating myeloblasts can be seen
Final diagnosis made by bone marrow biopsy

Molecular characteristics define the “risk” of the disease and dictates treatments
Prognostic scoring tools: revised international prognostic staging system (R-IPSS)
Management general paradigm
- Asymptomatic: with low-risk disease: monitoring
- Low-risk disease + symptoms due to anemia only: transfusions, erythrocyte stimulating agents, and treatment with Luspatercept
- MDS with isolated del(5q): treated with lenalidomide
- High-risk pts: treated with hypomethylating agents
- Only curative intervention: hematopoietic stem cell transplant (HSCT)