Jonathan J Edwards1, Naomi Seliktar2, Rachel White3, Steven D Heron4, Kimberly Lin3, Joseph Rossano3, Dimitri Monos5, Deborah Sesok-Pizzini6, Matthew J O'Connor3. 1. Department of Pediatrics, Division of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address: EdwardsJ6@email.chop.edu. 2. Technion Israel Institute of Technology, Haifa, Israel. 3. Department of Pediatrics, Division of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 4. Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 5. Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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.
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.
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