A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality

Margaret L MacMillan¹, Marie Robin², Andrew C Harris³, Todd E DeFor⁴, Paul J Martin⁵, Amin Alousi⁶, Vincent T Ho⁷, Javier Bolaños-Meade⁸, James L M Ferrara⁹, Richard Jones⁸, Mukta Arora¹⁰, Bruce R Blazar¹¹, Shernan G Holtan¹⁰, David Jacobsohn¹², Marcelo Pasquini¹³, Gerard Socie², Joseph H Antin⁷, John E Levine⁹, Daniel J Weisdorf¹⁴

Affiliations

¹ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. Electronic address: macmi002@umn.edu.
² Hôpital Saint Louis, Paris, France.
³ Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
⁴ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Biostatistics and Informatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
⁵ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
⁶ MD Anderson Cancer Center, Houston, Texas; Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin.
⁷ Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Dana-Farber Cancer Institute, Boston, Massachusetts.
⁸ Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Johns Hopkins University, Baltimore, Maryland.
⁹ Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan; Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin.
¹⁰ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
¹¹ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
¹² Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Children's National Medical Center, Washington, District of Columbia.
¹³ Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Medical College of Wisconsin, Milwaukee, Wisconsin.
¹⁴ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Department of Medicine, University of Minnesota, Minneapolis, Minnesota.

PMID: 25585275
PMCID: PMC4359643
DOI: 10.1016/j.bbmt.2015.01.001

A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality

Margaret L MacMillan et al. Biol Blood Marrow Transplant. 2015 Apr.

. 2015 Apr;21(4):761-7.

doi: 10.1016/j.bbmt.2015.01.001. Epub 2015 Jan 10.

Authors

Affiliations

¹ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. Electronic address: macmi002@umn.edu.
² Hôpital Saint Louis, Paris, France.
³ Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
⁴ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Biostatistics and Informatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
⁵ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
⁶ MD Anderson Cancer Center, Houston, Texas; Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin.
⁷ Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Dana-Farber Cancer Institute, Boston, Massachusetts.
⁸ Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Johns Hopkins University, Baltimore, Maryland.
⁹ Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan; Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin.
¹⁰ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
¹¹ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
¹² Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Children's National Medical Center, Washington, District of Columbia.
¹³ Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Medical College of Wisconsin, Milwaukee, Wisconsin.
¹⁴ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, Wisconsin; Department of Medicine, University of Minnesota, Minneapolis, Minnesota.

PMID: 25585275
PMCID: PMC4359643
DOI: 10.1016/j.bbmt.2015.01.001

Abstract

To develop a novel acute graft-versus-host disease (GVHD) risk score, we examined the GVHD clinical stage and grade of 1723 patients at the onset of treatment with systemic steroids. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. The overall response (complete response/partial response) rate 28 days after initiation of steroid therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the 1454 patients with standard risk (SR)-GVHD (44% [95% confidence interval (CI) 38% to 50%] versus 68% [95% CI, 66% to 70%], P < .001). Patients with HR-GVHD were less likely to respond at day 28 (odds ratio [OR], .3; 95% CI, .2 to .4; P < .001) and had higher risks of mortality (relative risk, 2.1; 95% CI, 1.7 to 2.6; P < .001) and transplant-related mortality (relative risk, 2.5; 95% CI, 2.0% to 3.2%, P < .001) than patients with SR-GVHD. This refined definition of acute GVHD risk is a better predictor of response, survival, and transplant-related mortality than other published acute GVHD risk scores. Patients with HR-GVHD are candidates for studies investigating new treatment approaches. Likewise, patients with SR-GVHD are candidates for studies investigating less toxic therapy.

Keywords: Allogeneic hematopoietic cell transplantation; Grading systems; Graft-versus-host disease; Risk score; Survival; Transplant-related mortality.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

**Figure 1**
Day 28 response by risk group. CR = complete response. PR = partial response.

**Figure 2**
Cumulative incidence (+/− 95% CI) of transplant related mortality at 6 months after onset of steroid therapy according to risk group.

**Figure 3**
Organ stages defining high-risk acute GVHD with % involved of total cohort of 1723 patients.

See this image and copyright information in PMC

References

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1. MacMillan ML, Weisdorf DJ, Wagner JE, et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant. 2002;8:387–94. - PubMed
1. Martino R, Romero P, Subira M, et al. Comparison of the classic Glucksberg criteria and the IBMTR Severity Index for grading acute graft-versus-host disease following HLA-identical sibling stem cell transplantation. International Bone Marrow Transplant Registry Bone Marrow Transplant. 1999;24:283–7. - PubMed
1. Weisdorf DJ, Hurd D, Carter S, et al. Prospective grading of graft-versus-host disease after unrelated donor marrow transplantation: a grading algorithm versus blinded expert panel review. Biol Blood Marrow Transplant. 2003;9:512–8. - PubMed
1. Cahn JY, Klein JP, Lee SJ, et al. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood. 2005;106:1495–500. - PMC - PubMed

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A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality

Affiliations

A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials