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. 2015 Feb 19;125(8):1333-8.
doi: 10.1182/blood-2014-10-609032. Epub 2015 Jan 15.

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

Shernan G Holtan  1 , Todd E DeFor  2 , Aleksandr Lazaryan  1 , Nelli Bejanyan  1 , Mukta Arora  1 , Claudio G Brunstein  1 , Bruce R Blazar  1 , Margaret L MacMillan  1 , Daniel J Weisdorf  1
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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.

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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.
See this image and copyright information in PMC

References

    1. Sehn LH, Alyea EP, Weller E, et al. Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion. J Clin Oncol. 1999;17(2):561–568. - PubMed
    1. Soiffer RJ, Lerademacher J, Ho V, et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117(25):6963–6970. - PMC - PubMed
    1. Alyea E, Neuberg D, Mauch P, et al. Effect of total body irradiation dose escalation on outcome following T-cell-depleted allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2002;8(3):139–144. - PubMed
    1. Sankoh AJ, Li H, D’Agostino RB., Sr Use of composite endpoints in clinical trials. Stat Med. 2014;33(27):4709–4714. - PubMed
    1. Bolanos-Meade J, Koreth J, Reshef R. A multi-center phase II trial randomizing novel approaches for graft-versus-host disease prevention compared to contemporary controls (1203). Available at: https://clinicaltrials.gov/ct2/show/NCT02208037. Accessed January 19, 2015.

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