- Clinical science
Myelodysplastic syndromes (MDS) are a group of hematological cancers in which malfunctioning pluripotent stem cells lead to hypercellularity and dysplasia of the bone marrow. This, in turn, leads to cytopenia of one or more cell lines (thrombocytopenia, erythrocytopenia, leukocytopenia). Most cases of MDS have a primary, idiopathic etiology, while a minority of cases are secondary to an underlying cause. MDS usually affects elderly patients and has a slowly progressive course. Clinical features vary depending on the type of MDS and the affected cell lines, and may include signs of anemia (e.g., fatigue, weakness, pallor), recurrent infections, and/or petechial bleeding. Diagnosis of MDS requires blood tests, bone marrow biopsy, and possibly genetic analysis. While mild cases may be closely monitored, severe disease typically requires blood transfusions supplemented with erythropoietin, vitamins, and, in some cases, granulocyte colony-stimulating factor. Medical therapy (e.g., chemotherapy or immunosuppressants) may also help to manage the disease, but allogenous stem cell transplantation is the only curative treatment. In 30% of cases, the disease progresses to acute myeloid leukemia.
Primary MDS (90% of cases) 
- Tends to occur in elderly patients
- Unknown etiology: likely due to spontaneous mutations
- Secondary MDS (10% of cases): caused by exogenous bone marrow damage
WHO Classification of Primary Myelodysplastic Syndromes
- The WHO classification distinguishes between eight different primary myelodysplastic syndromes, based on the number of dysplastic cell lines and the percentage of blasts in the bone marrow, among other criteria
- The most common types are refractory cytopenia with multilineage dysplasia, refractory anemia with ringed sideroblasts, and refractory cytopenia with unilineage dysplasia
- Asymptomatic in 20% of cases
- Dependent on the affected cell line
- Hepatosplenomegaly (uncommon)
CBC with peripheral smear
- Normocytic or macrocytic anemia (rarely microcytic) of refractory type (refractory anemia)
- Other possible findings
- Leukocytopenia and/or thrombocytopenia
- Nucleated RBCs, ringed sideroblasts, Howell-Jolly bodies, basophilic stippling
- Pseudo-Pelger-Huet anomaly
- Large, agranular platelets, and megakaryocytes (in MDS-F)
Bone marrow biopsy: hypercellular, dysplastic bone marrow with numerous cells of all three cell lines with blasts, megakaryocytes, etc.
- The amount of dysplastic cells depends on the type (see “Classification” above)
- Chromosome analysis: : In > 50% of patients, chromosomal aberrations can be detected at the time of diagnosis.
The therapeutic approach depends on a patient's presentation, age, and comorbidities. More aggressive therapy (e.g., chemotherapy, stem cell transplantation) is generally reserved for younger, healthier patients.
- Mild cytopenia: "watch and wait"
- Supportive treatment
- Mainstay of treatment: RBC and platelet transfusions depending on cell counts
- To compensate for the high cell turnover: vitamin supplementation (Vitamin B6, B12, folate)
- In cases of symptomatic anemia and low erythropoietin (EPO) levels: synthetic EPO
- In cases of neutropenia: granulocyte colony-stimulating factor
- If infection occurs: antibiotics
- Medical therapy:
- Allogenous stem cell transplant is the only curative option.
- Supportive treatment