Donor Selection, GVHD Prophylaxis Maximize 1-Year Survival After SCT

Brian C. Betts, MD, Vice Chair of Strategic Initiatives for the Transplant & Cellular Therapy Program at Roswell Park Comprehensive Cancer Center, outlines strategic clinical refinements implemented in Roswell Park’s stem cell transplantation (SCT) program to reduce graft-vs-host disease (GVHD), enhance immune reconstitution, and ultimately improve overall survival, which led to a 92% 1-year overall survival rate at the institution in 2024. A foundational element of their approach relies on posttransplant cyclophosphamide administered on days +3 and +4. This timing selectively prunes alloreactive T cells that typically drive GVHD, whereas systematically sparing essential immune effectors necessary for reconstitution and graft-vs-tumor effects. Following this, immunosuppressive therapy with tacrolimus and mycophenolate mofetil is initiated on day +5.

To further optimize patient outcomes, Roswell Park established a universal end point for immunosuppression by discontinuing tacrolimus without a taper on day +60, similar to protocols developed at Johns Hopkins Medicine. Discontinuing tacrolimus exposure on day +60 significantly accelerates posttransplant immune reconstitution, enhances the immunogenic response and effectiveness of posttransplant vaccinations, and eliminates long-term drug-induced toxicities that frequently complicate recovery.

In addition to the optimization of GVHD prophylaxis, the program overhauled its donor selection algorithms based on recipient outcomes and registry data from the Center for International Blood and Marrow Transplant Research. Although traditional clinical practice prioritizes fully matched sibling donors regardless of age, Roswell Park shifted toward prioritizing younger donors, ideally individuals under 30 years old. The data demonstrate that utilizing donors under age 40 yields a pronounced overall survival advantage for recipients, despite partial HLA mismatches. Pairing younger mismatched donors with modern posttransplant cyclophosphamide protocols delivers overall survival rates exceeding 80%, contributing to the benefit seen at Roswell Park.

Crucially, combining optimized posttransplant cyclophosphamide with younger donor selection produces a massive reduction in GVHD, driving severe GVHD incidence rates below 5%. Eliminating persistent transplant toxicities, such as chronic GVHD and severe cytopenias, allows clinicians to pivot their focus toward mitigating relapse, which remains the primary cause of posttransplant mortality. Without the burden of ongoing GVHD complications, the door opens to safely implement posttransplant maintenance therapies, comprehensively lowering relapse risk and elevating long-term outcomes.