Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study.

BACKGROUND: Despite the obvious survival benefit compared to that among waitlist patients, outcomes of positive crossmatch kidney transplantation (KT) are generally inferior to those of human leukocyte antigen (HLA)-compatible KT. This study aimed to compare the outcomes of positive complement-dependent cytotoxicity (CDC) crossmatch (CDC + FC+) and positive flow cytometric crossmatch (CDC-FC+) with those of HLA-compatible KT (CDC-FC-) after successful desensitization. METHODS: We retrospectively analyzed 330 eligible patients who underwent KTs between June 2011 and August 2017: CDC-FC- (n = 274), CDC-FC+ (n = 39), and CDC + FC+ (n = 17). Desensitization protocol targeting donor-specific antibody (DSA) involved plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab with/without bortezomib for positive-crossmatch KT. RESULTS: Death-censored graft survival and patient survival were not different among the three groups. The median estimated glomerular filtration rate was significantly lower in the CDC + FC+ group than in the compatible group at 6 months (P < 0.001) and 2 years (P = 0.020). Biopsy-proven rejection within 1 year of CDC-FC-, CDC-FC+, and CDC + FC+ were 15.3, 28.2, and 47.0%, respectively. Urinary tract infections (P < 0.001), Pneumocystis jirovecii pneumonia (P < 0.001), and cytomegalovirus viremia (P < 0.001) were more frequent in CDC-FC+ and CDC + FC+ than in CDC-FC-. CONCLUSIONS: This study showed that similar graft and patient survival was achieved in CDC-FC+ and CDC + FC+ KT compared with CDC-FC- through DSA-targeted desensitization despite the higher incidence of rejection and infection than that in compatible KT.

What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients.

BACKGROUND: The magnitude effects of human leukocyte antigen (HLA) mismatching on post-transplant outcomes of kidney transplantation remain controversial. We aim to quantitatively assess the associations of HLA mismatching with graft survival and mortality in adult kidney transplantation. METHODS: We searched PubMed, EMBASE and the Cochrane Library from their inception to December, 2016. Priori clinical outcomes were overall graft failure, death-censored graft failure and all-cause mortality. RESULTS: A total of 23 cohort studies covering 486,608 recipients were selected. HLA per mismatch was significant associated with increased risks of overall graft failure (hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.05-1.07), death-censored graft failure (HR: 1.09; 95% CI 1.06-1.12) and all-cause mortality (HR: 1.04; 95% CI: 1.02-1.07). Besides, HLA-DR mismatches were significant associated with worse overall graft survival (HR: 1.12, 95% CI: 1.05-1.21). For HLA-A locus, the association was insignificant (HR: 1.06; 95% CI: 0.98-1.14). We observed no significant association between HLA-B locus and overall graft failure (HR: 1.01; 95% CI: 0.90-1.15). In subgroup analyses, we found recipient sample size and ethnicity maybe the potential sources of heterogeneity. CONCLUSIONS: HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient's graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.

Clinical significance of donor-recipient HLA matching on survival after myeloablative hematopoietic cell transplantation from unrelated donors.

The application of unrelated donor hematopoietic cell transplantation can be expanded with the use of mismatched donors if human leukocyte antigen (HLA) disparity does not lead to increased morbidity and mortality. The rules that govern permissibility of HLA mismatches are not well defined. The International Histocompatibility Working Group in hematopoietic cell transplantation measured the risks associated with locus-specific disparity in 4796 patients transplanted for low, intermediate, or high-risk hematologic diseases. The permissibility of a given HLA mismatch is in part defined by the locus and by disease risk.

High resolution HLA class I and II typing and CTLp frequency in unrelated donor transplantation: a single-institution retrospective study of 69 BMTs.

UNLABELLED: The results of unrelated donor transplantation (URD-BMT) are difficult to analyze since the continuous advances in HLA typing technology allow the detection of new mismatches unknown at the time of transplantation. We sought to confirm that matched recipient-donor pairs are in fact often mismatched when advanced HLA typing techniques are used. We retrospectively studied the impact of the results of high resolution HLA typing for HLA class I (-A, -B, -C) and HLA class II (-DR, -DQ, -DP) loci, and cytotoxic T lymphocyte precursor (CTLp) frequency, on the outcome of 69 URD-BMT procedures. At the time of transplant, six (6/69) and two (2/69) donor-recipient pairs were mismatched for HLA class I (-A and -B by serology) and HLA class II, respectively, while one pair was mismatched for both HLA class I and II. Using high resolution DNA typing, HLA class I mismatches were found in 31 (45%) pairs and HLA class II mismatches in nine (13%) pairs. Twenty-three of the 69 pairs were HLA-C mismatched. Low CTLp frequencies were found among the 19 HLA class I matched pairs tested, and also in 5/14 mismatched pairs (of whom three had severe aGVHD). The overall survival of the cohort was 28 +/- 6%. Among the 33 patients who were fully matched with their donors, the survival rate was 66% in the 18 patients with a standard hematological risk and 9% in the 15 high risk patients. Only two of the 33 patients developed severe aGVHD, and only one had graft rejection. Among the 36 mismatched pairs, the survival rate was 31% in the 13 patients with a standard hematological risk and 8% in the 23 high risk patients. Sixteen of these 36 patients died from severe aGVHD and four had graft failure or rejection. Three of the 10 patients with only an HLA-C mismatch died from severe aGVHD, and two had graft rejection. IN CONCLUSION: (1) donor-recipient matching based on high resolution HLA class I and II DNA typing is associated with significantly better outcome after URD-BMT; (2) the results of URD-BMT with classical GVHD prevention are comparable to those of geno-identical BMT when donor and recipient are fully matched for HLA-A, -B, -C, -DRB1 and -DQB1 on the basis of high resolution typing; (3) CTLp frequencies do not correlate constantly with HLA class I matching, and our results fail to show that CTLp assay can distinguish between permissible and non-permissible class I mismatches; (4) clinical trials involving donor-recipient pairs with known HLA class I mismatches are needed to improve aGVHD prevention without increasing graft failure rate.