title: Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Allogeneic hematopoietic stem cell transplantation is associated with profound changes in levels of various cytokines. Emphasis has been placed on conditioning-associated mucosal damage and neutropenia and associated bacterial translocation as the initiating conditions predisposing to acute graft-versus-host disease. The post-transplant period is, however, also associated with increases in certain homeostatic cytokines. It is unclear how much the homeostatic drive to lymphocyte recovery and the production of cytokines from the engrafting donor immune system determine cytokine fluctuations in the peri- and immediate post-transplant period. The aim of this study was to examine the contributions of the conditioning regimen, donor engraftment, infections, and graft-versus-host disease to fluctuations in cytokines involved in homeostasis and inflammation.
  
  
  METHODS
  We examined the levels of 33 cytokines in relation to peri- and post-transplant events such as conditioning regimen, chimerism, and acute graft-versus-host disease in myeloablative, non-T cell-replete HLA-identical sibling donor stem cell transplantation for hematologic malignancies.
  
  
  RESULTS
  We identified two cytokine storms. The first occurred following conditioning and reached peak levels when all the leukocytes were at their lowest concentrations. The second cytokine storm occurred concurrently with hematopoietic reconstitution and subsided with the achievement of full donor lymphocyte chimerism.
  
  
  CONCLUSIONS
  Our results indicate that both recipient-related and donor-related factors contribute to the changes in cytokine levels in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using plasma samples drawn from patients enrolled in the ClinicalTrials.gov-registered trials NCT00467961 and NCT00378534.
authors: Hematology Branch, National Heart, Lung, and Blood Institute, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. melenhoj@nhlbi.nih.gov
authors: Jan Joseph
authors: JJ
authors: Melenhorst
authors: Xin
authors: X
authors: Tian
authors: Dihua
authors: D
authors: Xu
authors: Netanya G
authors: NG
authors: Sandler
authors: Philip
authors: P
authors: Scheinberg
authors: Angelique
authors: A
authors: Biancotto
authors: Priscila
authors: P
authors: Scheinberg
authors: John Phil
authors: JP
authors: McCoy
authors: Nancy F
authors: NF
authors: Hensel
authors: Zach
authors: Z
authors: McIver
authors: Daniel C
authors: DC
authors: Douek
authors: Austin John
authors: AJ
authors: Barrett
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010198:Pancytopenia / Q000276:immunology* / Q000473:pathology; D035781:Siblings; D058408:Th1-Th2 Balance; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D019653:Myeloablative Agonists