title: Pretransplant comorbidities predict severity of acute graft-versus-host disease and subsequent mortality.
abstract: Whether the hematopoietic cell transplantation comorbidity index (HCT-CI) can provide prognostic information about development of acute graft-versus-host disease (GVHD) and subsequent mortality is unknown. Five institutions contributed information on 2985 patients given human leukocyte antigen-matched grafts to address this question. Proportional hazards models were used to estimate the hazards of acute GVHD and post-GVHD mortality after adjustment for known risk variables. Higher HCT-CI scores predicted increased risk of grades 3 to 4 acute GVHD (P < .0001 and c-statistic of 0.64), and tests of interaction suggested that this association was consistent among different conditioning intensities, donor types, and stem cell sources. Probabilities of grades 3 to 4 GVHD were 13%, 18%, and 24% for HCT-CI risk groups of 0, 1 to 4, and ≥5. The HCT-CI was statistically significantly associated with mortality rates following diagnosis of grade 2 (hazard ratio [HR] = 1.24; P < .0001) or grades 3 to 4 acute GVHD (HR = 1.19; P < .0001). Patients with HCT-CI scores of ≥3 who developed grades 3 to 4 acute GVHD had a 2.63-fold higher risk of mortality than those with scores of 0 to 2 and did not develop acute GVHD. Thus, pretransplant comorbidities are associated with the development and severity of acute GVHD and with post-GVHD mortality. The HCT-CI could be useful in designing trials for GVHD prevention and could inform expectations for GVHD treatment trials.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Mohamed L
authors.identifier: http://orcid.org/0000-0001-5260-1981
authors.initials: ML
authors.lastname: Sorror
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Paul J
authors.identifier: http://orcid.org/0000-0001-9051-1215
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Rainer F
authors.identifier: http://orcid.org/0000-0002-9343-4099
authors.initials: RF
authors.lastname: Storb
authors.affiliation: City of Hope School of Medicine, Duarte, CA;
authors.forename: Smita
authors.identifier: http://orcid.org/0000-0002-3816-2238
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, and Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR;
authors.forename: Richard T
authors.identifier: http://orcid.org/0000-0002-8184-7099
authors.initials: RT
authors.lastname: Maziarz
authors.affiliation: Division of Hematology, University of Utah School of Medicine, Salt Lake City, UT; Pediatric Blood and Marrow Transplant Program, Primary Children's Medical Center, Huntsman Cancer Institute, Salt Lake City, UT;
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.affiliation: Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center, Denver, CO;
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Christopher
authors.initials: C
authors.lastname: Davis
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: H Joachim
authors.identifier: http://orcid.org/0000-0002-4426-9023
authors.initials: HJ
authors.lastname: Deeg
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Stephanie J
authors.identifier: http://orcid.org/0000-0003-2600-6390
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: David G
authors.identifier: http://orcid.org/0000-0002-8477-6919
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Brenda M
authors.identifier: http://orcid.org/0000-0002-9767-9739
authors.initials: BM
authors.lastname: Sandmaier
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA;
authors.forename: Frederick R
authors.identifier: http://orcid.org/0000-0002-1839-5069
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: Clinical Statistics Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Biostatistics, University of Washington School of Public Health, Seattle, WA.
authors.forename: Theodore A
authors.identifier: http://orcid.org/0000-0002-8182-3652
authors.initials: TA
authors.lastname: Gooley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality*; D006402:Hematologic Diseases / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D055815:Young Adult