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Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study

Lookup NU author(s): Dr Christian Harkensee, Dr Peter Middleton, Professor Andrew GenneryORCiD

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Abstract

Genetic risk factors contribute to adverse outcome of hematopoietic stem cell transplantation (HSCT). Mismatching of the HLA complex most strongly determines outcomes, whereas non-HLA genetic polymorphisms are also having an impact. Although the majority of HSCTs are mismatched, only few studies have investigated the effects of non-HLA polymorphisms in the unrelated HSCT and HLA-mismatched setting. To understand these effects, we genotyped 41 previously studied single nucleotide polymorphisms (SNPs) in 2 independent, large cohorts of HSCT donor-recipient pairs (n = 460 and 462 pairs) from a homogeneous genetic background. The study population was chosen to pragmatically represent a large clinically homogeneous group (acute leukemia), allowing all degrees of HLA matching. The TNF-1031 donor-recipient genotype mismatch association with acute GVHD grade 4 was the only consistent association identified. Analysis of a sub-group of higher HLA matching showed consistent associations of the recipient IL2-330 GT genotype with risk of chronic GVHD, and the donor CTLA4-CT60 GG genotype with protection from acute GVHD. These associations are strong candidates for prediction of risk in a clinical setting. This study shows that non-HLA gene polymorphisms are of relevance for predicting HSCT outcome, even for HLA mismatched transplants. (Blood. 2012;119(26):6365-6372)

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Author(s): Harkensee C, Oka A, Onizuka M, Middleton PG, Inoko H, Hirayasu K, Kashiwase K, Yabe T, Nakaoka H, Gennery AR, Ando K, Morishima Y, Japan Marrow Donor Program

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2012

Volume: 119

Issue: 26

Pages: 6365-6372

Print publication date: 28/06/2012

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology

URL: http://dx.doi.org/10.1182/blood-2012-01-406785

DOI: 10.1182/blood-2012-01-406785

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