- Clinical Transplantation. 2000 Apr; 14(2):162-6.
BACKGROUND: Despite the decreased incidence of acute rejection episodes and improvements in short and intermediate term graft survival with current immunosuppressive agents, there has been little progress in decreasing the morbidity and mortality from chronic rejection. This phenomenon may, in part, be related to the development of a humoral immune response with increases in anti-HLA antibodies, which presents as accelerated graft arteriopathy with intimal hyperplasia. METHODS: Based on prior experimental work, a pilot, prospective, randomized study was performed in 23 primary cardiac transplant recipients to determine whether the addition of prophylactic photopheresis to a cyclosporine, azathioprine and prednisone regimen was safe and resulted in decreased levels of panel reactive antibodies (PRA) and transplant arteriopathy. RESULTS: There was no difference between the two groups in regard to infection or acute rejection incidence. The photopheresis group had a significant reduction in PRA levels at two time points within the first 6 postoperative months. Coronary artery intimal thickness was significantly reduced in the photopheresis group at 1-yr (0.23 vs. 0.49 mm, p < 0.04) and 2-yr (0.28 vs. 0.46 mm, p < 0.02) follow-up compared with the control group. CONCLUSION: In this small pilot study, photopheresis is a safe, well-tolerated immunomodulatory technique that is capable of decreasing the severity of chronic rejection manifesting as post-transplant graft intimal hyperplasia.
BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
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METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
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RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
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CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
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