This patient should undergo allogeneic hematopoietic stem cell transplantation (HSCT). She has myelodysplastic syndrome (MDS), diagnosed by complete blood count results from an investigation of symptomatic pancytopenia. The monocytosis and mild macrocytosis are typical. Bone marrow examination is required to confirm the diagnosis and to provide prognostic information that can inform therapeutic recommendations. The International Prognostic Scoring System – Revised criteria weigh cytogenetics most heavily when determining risk. A complex karyotype places this patient in a high-risk group. Involvement of three cell lines and more than 5% marrow blasts specifies the highest risk group. In very high-risk disease, median survival is expected to be less than 1 year. Such a prognosis in a younger patient justifies the recommendation for allogeneic HSCT at diagnosis. Although transplantation is associated with significant risks, it is also the only curative therapy for MDS.

5-Azacytidine is appropriate for higher risk MDS but does not have curative potential. In a younger, fit patient, HSCT is a better choice. For older patients (generally older than 60 years) or those with significant comorbidities, 5-azacytidine would be an appropriate option.

Erythropoietic agents, such as epoetin and darbepoetin alfa, may improve hemoglobin levels in patients with symptomatic anemia and lower risk MDS but are not appropriate as single therapy for high-risk disease. This patient is at high risk of transforming from MDS to acute myeloid leukemia (AML); HSCT will mitigate that risk, but treatment with erythropoietin will not.

Because of this patient's high-risk MDS, observation would be inappropriate. The natural history of high-risk MDS is progression to AML. Because secondary AML is much harder to cure, primary therapy before transformation improves prognosis.