Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) are clonal myeloid neoplasms with ineffective haematopoiesis, dysplasia, cytopenias and risk of progression to AML.

• Incidence 4 per 100,000, increasing to 30 per 100,000 over 70 years.

• Causes: ageing, prior chemotherapy or radiotherapy, benzene, inherited syndromes.

• Subtypes (WHO): low blasts with SF3B1, del(5q), low blasts, increased blasts (MDS-IB1, IB2).

• Risk stratified by IPSS-M (cytogenetics, mutations, blasts, cytopenias): lower risk and higher risk.

• Median survival from 6 years (lower risk) to under 1.5 years (higher risk).

• Fatigue and anaemia symptoms, infections from neutropenia, bleeding from thrombocytopenia.

• Splenomegaly uncommon; autoimmune phenomena and vasculitis in some.

• Macrocytic anaemia, cytopenias, dysplastic cells in blood film.

• Marrow aspirate and trephine with dysplasia in 10% or more of a lineage, blast count, ring sideroblasts, cytogenetics (del5q, -7, complex), NGS panel (SF3B1, TP53, ASXL1, RUNX1, SRSF2).

• Exclude B12 and folate deficiency, copper deficiency, HIV, alcohol, medications, aplastic anaemia, PNH, hypoplastic AML.

• Erythropoietin level for therapy selection.

Lower risk

• Anaemia: epoetin alfa 40,000 to 60,000 units SC weekly (or darbepoetin 150 to 300 micrograms weekly) if erythropoietin below 500 U/L and low transfusion needs; luspatercept 1 to 1.75 mg/kg SC every 3 weeks for SF3B1 or ring sideroblast disease; lenalidomide 10 mg daily (21 days of 28) for del(5q).

• Imetelstat 7.1 mg/kg IV every 4 weeks for transfusion dependent patients failing ESA.

• Immunosuppression (antithymocyte globulin, ciclosporin) for young hypocellular disease.

• Transfuse for symptoms; iron chelation (deferasirox 10 to 20 mg/kg) for ferritin over 1000 and long life expectancy.

• Eltrombopag, romiplostim cautiously for thrombocytopenia.

Higher risk

• Allogeneic stem cell transplant for eligible patients (only curative therapy).

• Hypomethylating agents: azacitidine 75 mg/m2 SC or IV for 7 days every 28 days for at least 6 cycles (median survival gain about 9 months), or decitabine 20 mg/m2 for 5 days; oral decitabine/cedazuridine.

• Intensive chemotherapy in fit patients with high blasts as a bridge to transplant.

• Venetoclax combinations under evaluation.

Supportive: antibiotics prophylaxis for severe neutropenia, G-CSF for infection, vaccination.