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

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 hav...

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Bibliographic Details
Published in:Blood 2012-06, Vol.119 (26), p.6365-6372
Main Authors: Harkensee, Christian, Oka, Akira, Onizuka, Makoto, Middleton, Peter G., Inoko, Hidetoshi, Hirayasu, Kouyuki, Kashiwase, Koichi, Yabe, Toshio, Nakaoka, Hirofumi, Gennery, Andrew R., Ando, Kiyoshi, Morishima, Yasuo
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biological and medical sciences
Child
Child, Preschool
Cohort Studies
Female
Hematologic and hematopoietic diseases
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
HLA Antigens - genetics
Humans
Male
Medical sciences
Polymorphism, Single Nucleotide - physiology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
Retrospective Studies
Treatment Outcome
Unrelated Donors
Young Adult
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Summary: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 subgroup 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.
ISSN:0006-4971
1528-0020
1528-0020
DOI:10.1182/blood-2012-01-406785