title: Late altered organ function in very long-term survivors after allogeneic hematopoietic stem cell transplantation: a paired comparison with their HLA-identical sibling donor.
abstract: BACKGROUND
  Hematopoietic stem cell transplantation has become an established procedure worldwide. Severe early and late complications are well described. Little is known about more subtle changes in general health status of very long-term survivors. The study objective was to assess health status of very long-term survivors in comparison with their respective human leukocyte antigen-identical sibling donors.
  
  
  METHODS
  Case matched comparison in a cross-sectional cohort was performed in a tertiary university hospital and referral center for hematopoietic stem cell transplantation. Forty-four pairs of recipients and their respective donors with a very long-term (17.5 years median; 11-26 years range) follow up after allogeneic hematopoietic stem cell transplantation were included. A comparative clinical evaluation and examination of routine clinical chemistry tests was carried out.
  
  
  RESULTS
  Recipients more frequently had a lower Karnofsky score (P = 0.05), hypertension (P = 0.015) and dyslipidemia (P = 0.002) but were less likely to be smokers (P = 0.016). Recipients showed systematically lower glomerular filtration rates (P < 0.0001), higher liver function tests (P = 0.0004 for Aspartat-Amino-Transferase) and reduced thyroid function (P = 0.002) despite normal or near normal values, and independent of presence or absence of chronic graft-versus-host disease. Indicators of inflammation were more frequent in recipients (9 of 44) with ongoing chronic graft-versus-host disease as measured by higher C-reactive protein (P = 0.001) and higher von Willebrand factor (P = 0.002). Conclusions Clinically very long-term survivors after an allogeneic hematopoietic stem cell transplantation present more frequently with cardiovascular risk factors and with subtle signs of altered organ function compared to their sibling donors. Even minimal ongoing chronic graft-versus-host disease remains associated with elevated laboratory indicators of inflammation. The clinical significance of these findings needs to be defined.
authors.affiliation: Department of Hematology, University Hospital of Basel, Basel, Switzerland. ARovo@uhbs.ch
authors.forename: Alicia
authors.initials: A
authors.lastname: Rovó
authors.forename: Thomas
authors.initials: T
authors.lastname: Daikeler
authors.forename: Jörg
authors.initials: J
authors.lastname: Halter
authors.forename: Dominik
authors.initials: D
authors.lastname: Heim
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Tsakiris
authors.forename: Martin
authors.initials: M
authors.lastname: Stern
authors.forename: Tuomas
authors.initials: T
authors.lastname: Waltimo
authors.forename: Jan Dirk
authors.initials: JD
authors.lastname: Studt
authors.forename: Alan
authors.initials: A
authors.lastname: Tyndall
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: André
authors.initials: A
authors.lastname: Tichelli
mesh_terms: D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D006680:HLA Antigens / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000503:physiopathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D035781:Siblings; D015996:Survival Rate; D017741:Survivors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D002097:C-Reactive Protein