GTn repeat polymorphism in heme oxygenase-1 (HO-1) correlates with clinical outcome after myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation

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Tania Køllgaard, Brian Kornblit, Jesper Petersen, Tobias Wirenfeldt Klausen, Bo Kok Mortensen, Peter Brændstrup, Henrik Sengeløv, Estrid Høgdall, Klaus Müller, Lars Vindeløv, Mads Hald Andersen, Eivind Per thor Straten

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 ratelimiting 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.

Original languageEnglish
Article numbere0168210
JournalPLoS ONE
Issue number12
Number of pages8
Publication statusPublished - Dec 2016

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