title: Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes.
abstract: Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P < .001) and higher nonrelapse mortality at 2 years (38% versus 19%, P < .001) compared with non-ES patients, resulting in lower overall survival at 2 years (38% versus 54%, P < .001). There was no significant difference in relapse at 2 years (26% versus 31%, P = .772). Suppression of tumorigenicity 2, interleukin 2 receptor alpha, and tumor necrosis factor receptor 1 plasma biomarker levels were significantly elevated in ES patients. Our results illustrate the clinical significance and prognostic impact of ES on allogeneic HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES.
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology-Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chang
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
authors.forename: David
authors.initials: D
authors.lastname: Frame
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology-Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Erin
authors.initials: E
authors.lastname: Gatza
authors.affiliation: Department of Pediatrics, Division of General Pediatrics, University of Michigan, Ann Arbor, Michigan; Informatics Core of the Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: David A
authors.initials: DA
authors.lastname: Hanauer
authors.affiliation: University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Internal Medicine, Division of Hematology-Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: John M
authors.initials: JM
authors.lastname: Magenau
authors.affiliation: Department of Pharmacy, Rush University Medical Center, Chicago, Illinois.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Schultz
authors.affiliation: Department of Internal Medicine, Michigan State University, East Lansing, Michigan.
authors.forename: Hemasri
authors.initials: H
authors.lastname: Tokala
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology-Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology-Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.affiliation: Department of Internal Medicine, Division of Hematology-Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.affiliation: Department of Pediatric Hematology-Oncology, Indiana University, Indianapolis, Indiana.
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology-Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan. Electronic address: sungchoi@umich.edu.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Choi
mesh_terms: D005260:Female; D006085:Graft Survival / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D013577:Syndrome; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome
keywords: Cytokine storm; Engraftment syndrome; Hematopoietic cell transplantation