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Impact and predictors of positive response to desensitization in pediatric heart transplant candidates.

ABSTRACT: BACKGROUND:Desensitization, the process of reducing anti-human leukocyte antigen (HLA) antibodies in sensitized patients awaiting heart transplantation (HT), has unclear efficacy in pediatric HT candidates. METHODS:Pediatric HT candidates listed at our institution between January 1, 2013 and June 30, 2018 were retrospectively evaluated. Sensitization was defined as the calculated panel reactive antibody (cPRA) ? 10% with ? 1 a strong positive antibody. The desensitization response was defined as a ? 25% reduction in the mean fluorescence intensity (MFI) for ? 90% of the strong positive antibodies on follow-up panel reactive antibody (PRA) testing before waitlist removal, HT, or death (data available for 13 patients). RESULTS:The HT candidates were categorized as sensitized receiving desensitization therapy (ST, n?=?14), sensitized not receiving therapy (SNT, n?=?18), or non-sensitized (n?=?55). A desensitization response was observed in 8 (62%) of the ST upon repeat PRA testing, with the ST responders receiving more doses of intravenous immunoglobulin (IVIG) (8 vs 2, p < 0.05). The anti-HLA class I antibodies were particularly resistant for non-responders (p?=?1.9?×?10-4). The combination of homograft and ventricular assist device was more sensitizing than either alone (p?=?3.1?×?10-4). However, these sensitization risk factors did not impact the desensitization response. The ST was associated with a higher likelihood of remaining listed and a longer waitlist time without substantially impacting the HT rate, waitlist mortality, or early post-HT outcomes. CONCLUSIONS:Most ST patients had a favorable response to desensitization, with a dose-dependent response observed for IVIG. The anti-HLA class likely impacts the ST response, whereas traditional sensitization risk factors had no impact on the response.

SUBMITTER: Edwards JJ

PROVIDER: S-EPMC6827717 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Impact and predictors of positive response to desensitization in pediatric heart transplant candidates.

Edwards Jonathan J JJ Seliktar Naomi N White Rachel R Heron Steven D SD Lin Kimberly K Rossano Joseph J Monos Dimitri D Sesok-Pizzini Deborah D O'Connor Matthew J MJ

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20190825 11

<h4>Background</h4>Desensitization, the process of reducing anti-human leukocyte antigen (HLA) antibodies in sensitized patients awaiting heart transplantation (HT), has unclear efficacy in pediatric HT candidates.<h4>Methods</h4>Pediatric HT candidates listed at our institution between January 1, 2013 and June 30, 2018 were retrospectively evaluated. Sensitization was defined as the calculated panel reactive antibody (cPRA) ≥ 10% with ≥ 1 a strong positive antibody. The desensitization response ...[more]

PMID: 31672220

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Project description:Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy.Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy.Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates.

Project description:BackgroundHypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) may limit the use of aspirin in patients with cardiovascular diseases. Aspirin desensitization, which is a resource-intensive process, can offer such patients access to aspirin through the induction of temporary tolerance to aspirin. However, there is limited information on aspirin desensitization response in patients undergoing aspirin desensitization for cardiac indications in Asia.ObjectiveTo characterize patients who have undergone aspirin desensitization, evaluate their responses to the procedure, and identify risk factor(s) associated with failure of aspirin desensitization.MethodsWe conducted a retrospective review of medical records of patients who underwent aspirin desensitization in Singapore General Hospital between 1 June 2014 and 31 October 2017. Chi-square or Fisher exact test were used to analyze categorical data while independent samples t test or Wilcoxon rank-sum test were used for continuous data where appropriate. Multivariate logistic regression was used to identify predictors of aspirin desensitization failure.ResultsAll 214 patients in our study had cardiovascular indications for aspirin, with angioedema being the most common type of index reaction experienced with NSAIDs (n = 104, 48.6%). One hundred sixty-five patients (77.1%) achieved successful aspirin desensitization. In the selected sample analysis of patients with true NSAID hypersensitivity (n = 163), an index reaction of angioedema to NSAIDs was found to be significantly associated with a higher risk of failing aspirin desensitization (odds ratio, 7.21; 95% confidence interval, 1.94-26.71).ConclusionMajority of the patients who underwent aspirin desensitization in our institution were able to achieve tolerance to aspirin. An index reaction of angioedema to NSAIDs was identified as a risk factor for aspirin desensitization failure. This information can aid in the risk stratification of patients undergoing aspirin desensitization and ensure efficient resource allocation for this procedure.

Dataset Information

Impact and predictors of positive response to desensitization in pediatric heart transplant candidates.

Publications

Impact and predictors of positive response to desensitization in pediatric heart transplant candidates.

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