A 70-year-old otherwise fit and healthy female had been diagnosed 3 years previously with myelodysplastic syndrome (MDS; French–American–British [FAB] classification subtype refractory anaemia). Cytogenetic analysis was not done, as it was considered unnecessary in this age group. The patient had a haemoglobin concentration of 7.5 g/dl, white cell count 4 × 109/l, neutrophils 2.4 × 109/l and platelets 450 × 109/l at diagnosis. Red cell-transfusion therapy was commenced, with a transfusion interval of 3 weekly, to temporarily relieve symptoms of anaemia. A trial of recombinant human erythropoietin therapy with 30 000 units per week for 6 weeks, escalating to 60 000 units per week for 6 weeks, produced no erythroid response. Serum ferritin assayed after 3 years of red cell-transfusion dependence was 4500 mg/l. A bone marrow examination was repeated to confirm disease stability with a view to commencing iron-chelation therapy. Serum erythropoietin concentration was 2000 IU/l. The morphology confirmed World Health Organization (WHO) classification subtype refractory cytopenia with multilineage dysplasia, which was changed to a diagnosis of 5q- syndrome when cytogenetic analysis revealed all 20 metaphases showing del(5)(q13-33) as the sole abnormality.
Should a trial of recombinant erythropoietin have been offered?
Is there a therapeutic option to modify disease and promote erythropoiesis?
The 5q- syndrome, first described by Van den Berghe in 1974 and now recognized within the WHO classification1 as a separate nosological subtype of MDS, typically occurs in older female patients. The 5q- syndrome is a rare subtype of MDS comprising 2% of cases. However, MDS patients with the del(5q) cytogenetic abnormality and other WHO subtypes of MDS comprise a further 8% of all MDS patients.
Severe anaemia with a low/normal white cell count and a high platelet count is the typical presenting blood count profile. Bone marrow morphology is variable but characteristic monolobular megakaryocytes, relative erythroid hypoplasia and increased fibrosis are most commonly observed.2 Karyotype analysis reveals deletion of a critical region at 5q3.1. In the 5q- syndrome this is the sole karyotypic abnormality although additional abnormalities are often seen and these confer a poorer prognosis.2
The prognosis is relatively good for untreated patients with 5q- syndrome, with a median survival of 10 years and a low transformation rate to acute myeloid leukaemia of 10% in 10 years. Prognosis is poorer for patients with additional karyotypic abnormalities and particularly for patients with >5% blasts in the bone marrow.
Several erythropoiesis-stimulating protein (ESP) products are now available, including the longer-acting darbepoetin alfa. No ESP is licensed for therapy in MDS. Nevertheless, worldwide it has become standard management to consider selected MDS patients for ESP therapy, based upon data from a meta-analysis of phase II trials,3 phase II studies validating models to predict response4 and a single small phase III trial.5...