title: Failure-free survival in a prospective cohort of patients with chronic graft-versus-host disease.
abstract: Failure-free survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured failure-free survival in a prospective observational cohort of patients (n=575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median failure-free survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter failure-free survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio=2.06, 95% confidence interval: 1.29-3.32; P<0.003) and decreased survival (hazard ratio=1.51, 95% confidence interval: 1.04-2.18; P<0.03). These results show that fewer than half of patients on systemic treatment will be failure-free survivors at 1 year, and fewer than a third will reach 2 years without experiencing failure. Better treatments are needed for chronic graft-versus-host disease. Clinicaltrials.gov identifier: NCT00637689.
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic Phoenix, AZ, USA palmer.jeanne@mayo.edu.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chai
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Hematopoietic Stem Cell Transplantation National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.affiliation: Hematology and Stem Cell Transplant Program, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Pavletic
authors.affiliation: Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Division of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Vogelsang
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University Medical Center, CA, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Arai
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality*; D006402:Hematologic Diseases / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents