5-Azacytidine in myelodysplastic syndromes: a clinical practice guideline

Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoiesis that results in peripheral blood cytopenias and a marked propensity to progress to acute myelogenous leukemia. With 40,000-76,000 new cases per year in the USA, MDS is the commonest of the hematological malignancies and represents a significant burden of morbidity and premature death. Although supportive or palliative measures such as blood transfusion have long been the mainstay of management of MDS, disease-modifying medical therapies have recently become available. The most extensively characterized of these is 5-azacytidine (5-Aza); however, no consensus exists on how this agent should be deployed in MDS.

An overarching search of the literature identified 7019 citations investigating the treatment or management of MDS. Of those, six clinical articles of prospective phase 2-3 study design or meta-analyses were selected for inclusion in a systematic review of the evidence.

The Canadian Consortium on Evidence-Based Care in MDS recommends 5-Aza as first line therapy in all MDS patients with IPSS high-intermediate and high risk scores including WHO-defined AML (20-30% blasts) who cannot proceed immediately to allogeneic stem cell transplant. 5-Aza is not recommended as first line therapy with MDS patients with IPSS Low and Low-intermediate risk scores as there is no evidence that it alters the natural history of the disease nor is superior to standard therapy. The MDS consortium does not recommend combining 5-Aza with other agents at this time outside the context of a clinical trial.