A prognostic score for acute graft-versus-host disease based on biomarkers: A multicentre study

Blood and Marrow Transplant Clinical Trials Network

Research output: Contribution to journalArticle

Abstract

Background: Graft-versus-host disease (GVHD) is the major cause of non-relapse mortality after allogeneic haemopoietic stem-cell transplantation (SCT). The severity of symptoms at the onset of GVHD does not accurately defi ne risk, and thus most patients are treated alike with high dose systemic corticosteroids. We aimed to defi ne clinically meaningful risk strata for patients with newly diagnosed acute GVHD using plasma biomarkers. Methods: Between April 13, 2000, and May 7, 2013, we prospectively collected plasma from 492 SCT patients with newly diagnosed acute GVHD and randomly assigned (2:1) using a random number generator, conditional on the fi nal two datasets having the same median day of onset, into training (n=328) and test (n=164) sets. We used the concentrations of three recently validated biomarkers (TNFR1, ST2, and Reg3a) to create an algorithm that computed the probability of non-relapse mortality 6 months after GVHD onset for individual patients in the training set alone. We rank ordered the probabilities and identifi ed thresholds that created three distinct non-relapse mortality scores. We evaluated the algorithm in the test set, and again in an independent validation set of an additional 300 patients who underwent stem cell transplant and were enrolled on multicentre clinical trials of primary therapy for acute GVHD. Findings: In all three datasets (training, test, and validation), the cumulative incidence of 6-month non-relapse mortality signifi cantly increased as the Ann Arbor GVHD score increased. In the multicentre validation set, scores were 8% (95% CI 3-16) for score 1, 27% (20-34) for score 2, and 46% (33-58) for score 3 (p

Original languageEnglish (US)
Pages (from-to)e21-e29
JournalThe Lancet Haematology
Volume2
Issue number1
DOIs
StatePublished - 2015

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Graft vs Host Disease
Multicenter Studies
Biomarkers
Mortality
Stem Cell Transplantation
Receptors, Tumor Necrosis Factor, Type I
Adrenal Cortex Hormones
Stem Cells
Clinical Trials
Transplants
Incidence

ASJC Scopus subject areas

  • Hematology

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A prognostic score for acute graft-versus-host disease based on biomarkers : A multicentre study. / Blood and Marrow Transplant Clinical Trials Network.

In: The Lancet Haematology, Vol. 2, No. 1, 2015, p. e21-e29.

Research output: Contribution to journalArticle

Blood and Marrow Transplant Clinical Trials Network. / A prognostic score for acute graft-versus-host disease based on biomarkers : A multicentre study. In: The Lancet Haematology. 2015 ; Vol. 2, No. 1. pp. e21-e29.
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abstract = "Background: Graft-versus-host disease (GVHD) is the major cause of non-relapse mortality after allogeneic haemopoietic stem-cell transplantation (SCT). The severity of symptoms at the onset of GVHD does not accurately defi ne risk, and thus most patients are treated alike with high dose systemic corticosteroids. We aimed to defi ne clinically meaningful risk strata for patients with newly diagnosed acute GVHD using plasma biomarkers. Methods: Between April 13, 2000, and May 7, 2013, we prospectively collected plasma from 492 SCT patients with newly diagnosed acute GVHD and randomly assigned (2:1) using a random number generator, conditional on the fi nal two datasets having the same median day of onset, into training (n=328) and test (n=164) sets. We used the concentrations of three recently validated biomarkers (TNFR1, ST2, and Reg3a) to create an algorithm that computed the probability of non-relapse mortality 6 months after GVHD onset for individual patients in the training set alone. We rank ordered the probabilities and identifi ed thresholds that created three distinct non-relapse mortality scores. We evaluated the algorithm in the test set, and again in an independent validation set of an additional 300 patients who underwent stem cell transplant and were enrolled on multicentre clinical trials of primary therapy for acute GVHD. Findings: In all three datasets (training, test, and validation), the cumulative incidence of 6-month non-relapse mortality signifi cantly increased as the Ann Arbor GVHD score increased. In the multicentre validation set, scores were 8{\%} (95{\%} CI 3-16) for score 1, 27{\%} (20-34) for score 2, and 46{\%} (33-58) for score 3 (p",
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T1 - A prognostic score for acute graft-versus-host disease based on biomarkers

T2 - A multicentre study

AU - Blood and Marrow Transplant Clinical Trials Network

AU - Levine, John E.

AU - Braun, Thomas M.

AU - Harris, Andrew C.

AU - Holler, Ernst

AU - Taylor, Austin

AU - Miller, Holly

AU - Magenau, John

AU - Weisdorf, Daniel J.

AU - Ho, Vincent T.

AU - Bolanos Meade, F Javier

AU - Alousi, Amin M.

AU - Ferrara, James L M

PY - 2015

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