title: Graft-versus-host disease treatment: predictors of survival.
abstract: Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplant (HCT) is the major reason for nonrelapse mortality (NRM), and thus is a major determinant of long-term survival. Clinical trials of new aGVHD treatments are needed to identify approaches that will ultimately improve upon HCT survival. At present, it is not clear how quickly response to GVHD treatment needs to be established to reliably categorize patients at high risk for death or to promptly identify those who might benefit from alternate treatment. Therefore, we analyzed time to response from onset of aGVHD treatment in 180 patients who were enrolled on a national, randomized, phase II aGVHD treatment clinical trial whose initial treatment of GVHD consisted of high-dose steroids plus a second immunosuppressive agent. The aim of this analysis was to determine whether time to aGVHD treatment response predicts patient outcomes, especially survival. We used response at 14, 28, and 56 days from initiation of aGVHD treatment to categorize patients for NRM and survival. Multivariate analyses and specificity/sensitivity analyses identified that day 28 response (complete or partial response) best categorized patients by NRM and survival at 9 months from start of aGVHD treatment. If verified as a reliable predictor of late outcomes following other aGVHD treatment approaches, day 28 response should serve as a standard early endpoint for future trials of aGVHD therapy.
authors.affiliation: Departments of Pediatrics and Internal Medicine, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5941, USA. jelevine@umich.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: Brent
authors.initials: B
authors.lastname: Logan
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.forename: Amin M
authors.initials: AM
authors.lastname: Alousi
authors.forename: Vincent
authors.initials: V
authors.lastname: Ho
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D004167:Diphtheria Toxin / Q000008:administration & dosage; D000068800:Etanercept; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology; D006402:Hematologic Diseases / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D015649:Pentostatin / Q000008:administration & dosage; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D004167:Diphtheria Toxin; D007074:Immunoglobulin G; D007376:Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D015649:Pentostatin; D000068800:Etanercept; D008775:Methylprednisolone