Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation

The success of allogeneic hematopoietic cell transplantation (HCT) is typically assessed as individual complications, including graft-versus-host disease (GVHD), relapse, or death, yet no one factor can completely characterize cure without ongoing morbidity. We examined a novel composite end point of GVHD-free/relapse-free survival (G RFS) in which events include grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. In 907 consecutive University of Minnesota allogeneic HCT recipients (2000-2012), 1-year GRFS was 31% (95% confidence interval [Cl] 28-34). Regression analyses showed age, disease risk, and donor type significantly influencing GRFS. Adults age 21+ had 2-fold worse GRFS vs children; GRFS did not differ beyond age 21. Adjusted for conditioning intensity, stem cell source, disease risk, age, and transplant year, HLA-matched sibling donor marrow resulted in the best GRFS (51%, 95% Cl 46-66), whereas HLA-matched sibling donor peripheral blood stem cells were significantly worse (25%, 95% Cl 20-30, P =.01). GRFS after umbilical cord blood transplants and marrow from matched unrelated donors were similar (31%, 95% CI 27-35 and 32%, 95% Cl 22-42, respectively). Because GRFS measures freedom from ongoing morbidity and represents ideal HCT recovery, GRFS has value as a novel end point for benchmarking new therapies.