The influence of conventional and cross-reactive group HLA matching on cardiac transplant outcome: an analysis from the United Network of Organ Sharing Scientific Registry.
BACKGROUND
The short tolerable cold ischemia time and the importance of other risk factors have generally superseded the role of HLA matching in the allocation of donor hearts. Recent advances in the accuracy and time required to perform HLA typing and crossmatching, however, have led us to re-examine the United Network of Organ Sharing Transplant Registry for the effects of the HLA incompatibility on outcome in relation to other possible risk factors.


METHODS
These include conventional HLA-A, -B, and cross-reactive group (CREG) mismatching (mm), HLA-DR mm, pretransplantation panel-reactive antibody (PRA), recipient and donor race and donor age, cold ischemia time, and the pretransplantation use of either a left ventricular assist device or an intra-aortic balloon pump.


RESULTS
Three-year survival was clearly inferior in non-white (0.6921) as compared with white (0.7632) recipients, but this difference could not be accounted for by the degree of donor-recipient HLA mm that had occurred by chance. Nevertheless, the degree of mm that did occur seemed to have an impact on survival. The importance of HLA-DR mm was confirmed, and it ranked only behind the use of an assist device and recipient race in the multivariate analysis. HLA-A and B mm exerted an additional effect, but this was only true in white recipients. Of these, HLA-A achieved statistical significance as an independent risk factor. In general, CREG mm was not a significant variable. However, more than twice as many 0-1 or 0-2 CREG, 0 DR mm as compared with 0-1 or 0-2 A,B, 0 DR mm transplants enjoyed approximately equal and very good 1- and 3-year survival. Assuming no change is cold ischemia time, the potential number of 0 CREG, 0 DR mm, ABO-compatible transplants that could be achieved when an Organ Procurement Organization had 50-100 patients on their waiting list was calculated. The surprisingly high frequency of approximately 24-36% suggests that this favorable match could be considered along with other important factors in the local allocation process. When pretransplantation PRA was analyzed as a continuous variable from 0 to 100%, it was a highly significant risk factor, but this effect was more strikingly evident when the PRA was analyzed in 20% increments above zero. Recently, left ventricular assist device usage has become increasingly common, and it has been associated with strikingly increased pretransplantation PRA levels. When they occur together, the data indicates that these patients are at a very high risk for graft failure.


CONCLUSIONS
We believe that newer typing and crossmatching techniques make it possible to add HLA criteria to the allocation protocol of donor cardiac organs and would lead to improved long-term survival.
Thompson
J S
JS
The Department of Medicine, University of Kentucky, Lexington 40536, USA.
Thacker
L R
LR
Takemoto
S
S
D016009:Chi-Square Distribution; D003429:Cross Reactions; D005006:Ethnicity; D005260:Female; D006085:Graft Survival; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D008297:Male; D012042:Registries; D016019:Survival Analysis; D013997:Time Factors; D009927:Tissue and Organ Procurement; D016896:Treatment Outcome; D014481:United States; D044465:White People
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens