Oral Decitabine and Cedazuridine Maintenance Post-HSCT: Promising Strategy in High-Risk AML and MDS

Study Background and Disease Burden

Acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are clonal hematological malignancies characterized by ineffective hematopoiesis and risk of progression to bone marrow failure or leukemic transformation. Allogeneic haematopoietic stem-cell transplantation (HSCT) remains a potentially curative option, particularly for patients with high-risk disease features. However, relapse post-HSCT is the leading cause of treatment failure and mortality, especially in patients categorized as very high risk, defined by adverse genetic, molecular, or clinical prognostic factors. Despite advancements in transplantation strategies, relapse rates remain substantial, underscoring the unmet need for effective maintenance therapies to sustain remission and improve long-term outcomes.

Hypomethylating agents (HMAs) such as decitabine have demonstrated efficacy in AML and MDS by reversing aberrant DNA hypermethylation, restoring tumor suppressor gene expression, and inducing cellular differentiation or apoptosis. Incorporating HMAs as maintenance therapy post-HSCT aims to prevent relapse by targeting residual leukemic clones. Oral formulations, such as the combination of decitabine and cedazuridine (ASTX727), a cytidine deaminase inhibitor enhancing decitabine bioavailability, offer convenient administration compared to parenteral routes, potentially improving adherence and quality of life. Previous studies combining HMAs with donor lymphocyte infusion (DLI) suggest synergistic immunomodulatory effects that might further reduce relapse risk.