Clinical Lung and Heart/Lung Transplantation
Does human leukocyte antigen matching influence the outcome of lung transplantation? an analysis of 3,549 lung transplantations

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Abstract

Background and Objective: Human leukocyte antigen (HLA) compatibility has been shown to improve the outcome of renal and cardiac transplantation. However, its impact on outcome following lung transplantation is not clear, with several single-center studies reporting inconsistent results. We studied the influence of HLA matching on survival and the development of rejection and obliterative bronchiolitis after lung transplantation, using data from the United Network for Organ Sharing/International Society for Heart and Lung Transplantation registry.

Methods

The study population included adult patients who received cadaveric lung transplants between October 1987 and June 1997 for whom HLA data were available. Two cohorts were examined, depending on the era of transplantation: (1) October 1987 to June 1997 (n = 3,549): Differences in actuarial survival as stratified by either the total number of HLA mismatches or the number of mismatches at each HLA locus were determined using a log-rank test. Multivariate logistic regression models were developed to determine independent predictors of survival at 1, 3, and 5 years following lung transplantation. (2) April 1994 to June 1997 (n = 1,796): The association of HLA mismatching with acute rejection and obliterative bronchiolitis was determined using a chi-squared analysis.

Results

Only 164 patients (4.6%) received lung grafts with 2 or fewer HLA mismatches. Univariate analyses demonstrated a significant difference in post-transplant survival by mismatch level, with the total number of HLA mismatches (p = 0.0008) and mismatching at the HLA-A locus (p = 0.002) associated with worse survival. Multivariate logistic regression demonstrated that the number of mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality (incremental odds ratios 1.18, p = 0.01, and 1.15, p = 0.03, respectively). The total number of HLA mismatches predicted 3- and 5-year mortality (incremental odds ratios 1.13 at 3 years, p = 0.0004, and 1.14 at 5 years, p = 0.0002). However, other covariates such as repeat transplantation, transplantation for congenital heart disease, advanced recipient age, and an early era of transplantation were stronger predictors of mortality. We found no significant association between HLA mismatching and the development of obliterative bronchiolitis, although there was an association between mismatching at the HLA-A locus and acute rejection episodes requiring hospital admission (p = 0.008). We also found no association between mismatching at the HLA-B locus and rejection episodes requiring either hospitalization or the alteration of anti-rejection medications (p = 0.034).

Conclusion

Although the number of HLA mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality and the total number of mismatches predicted 3- and 5-year mortality following lung transplantation, the effect of each covariate was small in this multicenter study of 3,549 patients. Further close follow-up of registry patients is necessary to determine the effect of HLA matching on long-term survival and freedom from obliterative bronchiolitis and rejection following lung transplantation. A prospective study of HLA matching for lung transplantation should not yet be considered in view of the small number of grafts with 2 or fewer mismatches and the modest effect of HLA matching on outcome.

Section snippets

Patients and methods

The initial study cohort included 4,782 adult cadaveric lung transplant recipients operated on between October 1987 and June 1997. Data were retrieved from the United Network for Organ Sharing/International Society for Heart and Lung Transplantation registry. Exclusion criteria included incomplete HLA data (n = 807), pediatric recipients (n = 264), non-cadaveric donors (n = 82), inadequate or insufficient survival data (n = 73), and multiorgan transplants (n = 7), thus providing complete data

Results

The distribution of the total number of HLA mismatches is illustrated in Table I. Only 4.6% of the patients in this study (164/3,549) had 0, 1, or 2 total mismatches.

The actuarial survival of lung transplantation patients according to the total number of HLA mismatches and the number of mismatches at the HLA-A, HLA-B, and HLA-DR loci are shown in Figure 1 and Figure 2. We found a significant difference in survival when transplants were stratified by either the total mismatch level (p =

Discussion

The results of this study, examining a large cohort of patients who underwent lung transplantation, indicated that HLA matching does not have an important clinical impact on outcome after transplantation. This is in contrast with both renal and cardiac transplantation, in which HLA matching has a beneficial effect on outcome.1, 3 In this study univariate analyses indicated that 2 or fewer total HLA mismatches or limited mismatching at the HLA-A locus were associated statistically with an

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