In this commentary in Blood, Drs. Stephen Forman and Jacob Rowe note that although allogeneic HCT in patients with relapsed acute leukemia in second remission (CR2) can be effective, most patients are not actually able to achieve CR2. The result, the authors note, is that “the long-term outcomes of such a strategy are poor: the 5-year overall survival from first relapse for patients with acute leukemia is only approximately 10%.” More effective minimal residual disease detection during first remission may be a useful bridging treatment between relapse and transplantation, according to the authors, especially if it leads to earlier reinduction therapy in appropriate patients who can then undergo HCT before overt relapse.