title: Cytokine Profile of Engraftment Syndrome in Pediatric Hematopoietic Stem Cell Transplant Recipients.
abstract: The biology of engraftment syndrome is poorly understood, and the degree of overlap with acute graft-versus-host disease (GVHD) is unclear. To understand engraftment syndrome better, plasma cytokine profiles were evaluated in 56 pediatric allogeneic bone marrow transplant recipients before transplant, on the day of stem cell infusion, and weekly until day +100. Patients were divided into 4 groups: those with isolated engraftment syndrome (n = 8), acute GVHD (n = 12), both engraftment syndrome and acute GVHD (n = 4), and neither engraftment syndrome nor acute GVHD (n = 32). Engraftment syndrome was observed a median of 13.5 days (range, 10 to 28) after transplant, whereas acute GVHD was diagnosed a median of 55 days (range, 19 to 95) after transplant. Four patients developed both engraftment syndrome at a median of 10.5 days (range, 10 to 11) and acute GVHD at a median of 35 days (range, 23 to 56) after stem cell infusion. Median plasma levels of IL-1β, IL-6, IL-12, IL-4, and IL-13 were significantly elevated in patients with isolated engraftment syndrome when compared with isolated acute GVHD. A rise of proinflammatory cytokines (IL-1β, IL-6, and IL-12) was followed by surge in anti-inflammatory cytokines (IL-4 and IL-13) in patients with isolated engraftment syndrome. The observation of elevated IL-1β suggests that engraftment syndrome could be an inflammasome mediated phenomenon.
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Pooja.khandelwal@cchmc.org.
authors.forename: Pooja
authors.initials: P
authors.lastname: Khandelwal
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mellor-Heineke
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Najibah
authors.initials: N
authors.lastname: Rehman
authors.affiliation: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Adam
authors.initials: A
authors.lastname: Lane
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Kristi
authors.initials: K
authors.lastname: Smiley
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Joyce
authors.initials: J
authors.lastname: Villanueva
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Grimley
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D058847:Inflammasomes / Q000276:immunology; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011446:Prospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D016207:Cytokines; D007166:Immunosuppressive Agents; D058847:Inflammasomes; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D016572:Cyclosporine
keywords: Acute GVHD; Cytokine; Cytokine storm; Engraftment syndrome; IL-1β