Clinical significance of minimal residual disease in patients with acute leukaemia undergoing haematopoietic stem cell transplantation

In patients with acute leukaemia, the relative risk of relapse influences the choice between chemotherapy and haematopoietic stem cell transplantation (HSCT). The demonstration that minimal residual disease (MRD) is the strongest overall prognostic indicator and can identify patients who are unlikely to be cured by standard chemotherapy has added a powerful new factor to consider when making this decision. There is substantial data indicating that the likelihood of relapse after transplant is directly correlated with levels of MRD before transplant. This knowledge can be used to adjust the timing of HSCT, and guide the selection of donor, conditioning regimen, and post-HSCT strategies to maximize the graft-versus-leukaemia effect. Because MRD emerging post-transplant carries a dire prognosis, its detection can trigger withdrawal of immunosuppression, additional cellular and molecular therapies, or preparations for a second HSCT. Although it is not yet clear whether any of these actions will significantly improve outcome, it is likely that they will be most effective for patients with a relatively low tumour burden, who can be identified only through MRD testing. In this article, we review the clinical significance of MRD in the context of autologous and allogeneic HSCT.