Clinical significance of HLA-E*0103 homozygosity on survival after allogeneic hematopoietic stem-cell transplantation.
BACKGROUND
Hematopoietic stem-cell transplantation is a well-established treatment in various hematologic malignancies, but the outcome depends on disease relapse, infections, and the development and severity of acute and chronic graft-versus-host disease. Some evidence has revealed an important role for the nonclassical major histocompatibility complex class I molecules in transplantation, most notably human leukocyte antigen (HLA)-E. This study evaluates the impact of HLA-E alleles on transplantation outcome after HLA-matched allogeneic HSCT.


METHODS
We genotyped DNA for HLA-E polymorphism from 83 recipients and their respective donors by real-time polymerase chain reaction after melting curve analysis and compared the results with clinical outcome.


RESULTS
HLA-E*0103 homozygous patients showed a higher probability of overall survival (P=0.003) and disease-free survival (P=0.001) in a univariate model. Cox regression analysis confirmed HLA-E*0103, 0103 (P=0.006; relative risk 1.12; 95% confidence interval 0.31-1.94) and early stage of disease (P=0.005; relative risk 1.16; 95% confidence interval 0.45-1.86) as independent factors improving overall survival. Moreover, homozygosity for HLA-E*0103 was associated with a significant decreased incidence of transplant-related mortality (P=0.01).


CONCLUSIONS
We found an association between HLA-E*0103 homozygosity and the significant reduction of transplant-related mortality in related and unrelated HSCT. The risk of posttransplant complications was significantly reduced when the donor possesses the HLA-E*0103, 0103 genotype, and this was translated in a better overall survival.
Danzer
Martin
M
Red Cross Transfusion Service of Upper Austria, Linz, Austria. martin.danzer@o.roteskreuz.at
Polin
Helene
H
Pröll
Johannes
J
Haunschmid
Reinhard
R
Hofer
Katja
K
Stabentheiner
Stephanie
S
Hackl
Christa
C
Kasparu
Hedwig
H
König
Josef
J
Hauser
Hanns
H
Binder
Michaela
M
Weiss
Richard
R
Gabriel
Christian
C
Krieger
Otto
O
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D055815:Young Adult; D000097625:HLA-E Antigens
D017931:DNA Primers; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens