The mythological chimera and new era of relapse prediction post-transplant

Allogeneic hemopoietic stem cell transplantation is the treatment of choice for high-risk or relapsed acute leukemia. However, unfortunately, relapse post-transplant continues to be the most common cause of treatment failure with 20-80% of patients relapsing based on disease risk and status at transplant. Advances in molecular profiling of different hematological malignancies have enabled us to monitor low level disease before and after transplant and develop a more personalized approach to the management of these disease including early detection post-transplant. While, in general, detectable disease by morphology remains the gold standard to diagnosing relapse, multiple approaches have allowed detection of cancer cells earlier, using peripheral blood-based methods with sensitivities as high as 1:10⁶, together called minimal/measurable residual disease (MRD) detection. However, a in significant number of patients with acute leukemia where no such molecular markers exist it remains challenging to detect early relapse. In such patients who receive transplantation, chimerism monitoring remains the only option. An increase in mixed chimerism in post allogeneic HCT patients has been correlated with relapse in multiple studies. However, chimerism monitoring, while commonly accepted as a tool for assessing engraftment, has not been routinely used for relapse detection, at least in part because of the lack of standardized, high sensitivity, reliable methods for chimerism detection. In this paper, we review the various methods employed for MRD and chimerism detection post-transplant and discuss future trends in MRD and chimerism monitoring from the viewpoint of the practicing transplant physician.