Reduced-intensity conditioning (RIC) has made allogeneic hematopoietic cell transplantation (allo-HCT) accessible to older patients and those who can’t tolerate myeloablative conditioning. The trade-off is less pre-transplant cytoreduction, and relapse remains a major limitation, especially in acute myeloid leukemia with adverse molecular or cytogenetic features and in patients who are MRD-positive at transplant.

Radioimmunotherapy (RIT) is being explored as a way to intensify leukemia-directed radiation without proportionally increasing radiation exposure to nonhematopoietic organs. A monoclonal antibody recognizes an antigen expressed in the hematopoietic compartment and carries a therapeutic radionuclide to the marrow, spleen and other sites of disease. It can be incorporated into an RIC transplant regimen.

The biological rationale, clinical experience, and emerging α-emitter platforms are reviewed in Frontiers. The clinical evidence remains early phase, but it shows that substantial radiation doses can be concentrated in hematopoietic tissues with reliable donor engraftment.