title: (GT)n Repeat Polymorphism in Heme Oxygenase-1 (HO-1) Correlates with Clinical Outcome after Myeloablative or Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation.
abstract: Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation and it has been shown to exert anti-inflammatory functions. In humans a (GT)n repeat polymorphism regulates the expression of HO-1. We conducted fragment length analyses of the (GT)n repeat in the promotor region of the gene for HO-1 in DNA from donors and recipients receiving allogeneic myeloablative- (MA) (n = 110) or nonmyeloablative- (NMA-) (n = 250) HCT. Subsequently, we compared the length of the (GT)n repeat with clinical outcome after HCT. We demonstrated that transplants from a HO-1high donor after MA-conditioning (n = 13) is associated with higher relapse incidence at 3 years (p = 0.01, n = 110). In the NMA-conditioning setting transplantation of HO-1low donor cells into HO-1low recipients correlated significantly with decreased relapse related mortality (RRM) and longer progression free survival (PFS) (p = 0.03 and p = 0.008, respectively). Overall, our findings suggest that HO-1 may play a role for the induction of GVT effect after allogeneic HCT.
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, 54P4, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Tania
authors.initials: T
authors.lastname: Køllgaard
authors.affiliation: Allogeneic Hematopoietic Cell Transplantation Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Brian
authors.initials: B
authors.lastname: Kornblit
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, 54P4, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, 54P4, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Tobias Wirenfeldt
authors.initials: TW
authors.lastname: Klausen
authors.affiliation: Allogeneic Hematopoietic Cell Transplantation Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Bo Kok
authors.initials: BK
authors.lastname: Mortensen
authors.affiliation: Allogeneic Hematopoietic Cell Transplantation Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Brændstrup
authors.affiliation: The Bone Marrow Transplantation Unit, Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Sengeløv
authors.affiliation: Department of Pathology, Molecular Unit, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.affiliation: Department of Pediatrics and Adolescent Medicine and Institute of Inflammation Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Müller
authors.affiliation: Allogeneic Hematopoietic Cell Transplantation Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Vindeløv
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, 54P4, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, 54P4, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Thor Straten
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D018900:Dinucleotide Repeats; D018572:Disease-Free Survival; D005260:Female; D006402:Hematologic Diseases / Q000235:genetics / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D019172:Transplantation Conditioning; D061349:Unrelated Donors
chemical_list: C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1