Acute myeloid leukaemia relapse after allogeneic haematopoietic stem cell transplantation: Mechanistic diversity and therapeutic directions

Summary Emerging biological and clinical data, along with advances in new technologies, have exposed the mechanistic diversity in post‐haematopoietic stem cell transplant (HCT) relapse. Post‐HCT relapse mechanisms are relevant for guiding sophisticated selection of therapeutic interventions and identification of areas for further research. Clonal evolution and emergence of resistant leukemic strains is a common mechanism shared by relapse post‐chemotherapy and post‐HCT, other mechanisms such as leukemic immune escape and donor T cell exhaustion are unique entities to post‐HCT relapse. Due to diversity in the mechanisms behind post‐HCT relapse, the subsequent clinical approach relies on clinician discretion, rather than objective evidence. Lack of standardized selection based on post‐HCT relapse mechanism(s) could be a contributing factor to observed poor outcomes. Therapeutic strategies including donor lymphocyte infusion (DLI), second transplant, immunotherapies, hypomethylating agents, and targeted strategies are supported options and efficacy may be enhanced when post‐HCT AML relapse mechanism is established and guides treatment selection. This review aims, through compilation of supporting studies, to describe mechanisms of post‐HCT relapse and their implications for subsequent treatment selection and inspiration for future research.