Are Hypomethylating Agents Replacing Induction-Type Chemotherapy before Allogeneic Stem Cell Transplantation in Patients with Myelodysplastic Syndrome?

Cytoreductive treatment before allogeneic hematopoietic stem cell transplantation (allo-SCT) with the objective of reducing the incidence of disease relapse post-transplant in patients with myelodysplastic syndrome (MDS) is a matter of debate. The achievement of complete remission (CR) before allo-SCT improves post-transplantation outcome, although it is not clear whether this reflects the selection of patients with more responsive disease or is related to a reduction in disease burden. Higher CR rates in patients with MDS are obtained with induction chemotherapy (ICT) than with hypomethylating agents (HMAs), although HMAs may be active in patients with complex karyotypes in whom ICT almost invariably fails. Furthermore, HMAs have a good toxicity profile compared with ICT and may therefore be considered especially in older patients and in patients with comorbidities. However, all interventions aimed at reducing disease burden before allo-SCT expose patients to the risk of complications, which may prevent them from undergoing transplantation. Therefore, up-front allo-SCT is an option, particularly for patients with life-threatening cytopenias. In this review we discuss the main pretransplant therapeutic approaches and propose a decision-model based on clinical considerations. However, only prospective randomized trials can address the issue definitively.