Why is a 3-year NRM following allogeneic transplantation still stuck at approximately 20%?

Whether and when to recommend an allogeneic stem cell transplant (SCT) for a patient with leukemia is a treatment decision that rests on determining whether the transplant or non-transplant option carries the greatest probability of 3-5-year survival. While SCT confers a greater possibility of leukemia cure, the decision to transplant has to be made in the light of the high chance of treatment-related mortality (TRM) that follows the allograft. Here we identify that current estimates of a 20% 3-year TRM hold largely true for a variety of leukemias, diverse types of conditioning regimen, and varied donor-recipient compatibility across a wide age-range. While there is a wide spectrum of causes of death in the first few months after SCT, they usually stem from a limited set of immediate post-transplant complications, including those induced by the conditioning regimen, post-transplant endovascular damage, gut dysbiosis, graft-versus-host disease, and immunodeficiency causing viral reactivation. As we better understand and improve preventative treatments for these initiating events there is a real expectation that TRM will continue to fall to levels well below 10% within the next decade.