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, 125 (8), 1333-8

Composite End Point of Graft-Versus-Host Disease-Free, Relapse-Free Survival After Allogeneic Hematopoietic Cell Transplantation

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Composite End Point of Graft-Versus-Host Disease-Free, Relapse-Free Survival After Allogeneic Hematopoietic Cell Transplantation

Shernan G Holtan et al. Blood.

Abstract

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 (GRFS) 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 [CI] 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% CI 46-66), whereas HLA-matched sibling donor peripheral blood stem cells were significantly worse (25%, 95% CI 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% CI 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.

Figures

Figure 1
Figure 1
Kaplan-Meier estimates. OS, DFS, and GRFS.
Figure 2
Figure 2
Distribution of individual components of GRFS. (A) Age (P < .01), (B) conditioning regimen (P < .01), (C) stem cell/donor type (P < .01), and (D) cause of death by donor type. MA, myeloablative conditioning.
Figure 3
Figure 3
Adjusted Kaplan-Meier estimates of GRFS based upon disease risk. Estimates combine pediatric and adult patients and are adjusted for conditioning intensity, stem cell source, age, and year of transplant.
Figure 4
Figure 4
Kaplan-Meier estimate of GRFS. Estimates are based upon donor type, adjusted for conditioning intensity, stem cell source, disease risk, age, and year of transplant.

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