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

Edwards, Janice G.; Seliktar, Naomi; White, Rachel; Heron, S.; Lin, Kimberly Y.; Rossano, Joseph W.; Monos, Dimitri; Sesok‐Pizzini, Deborah; O’Connor, Matthew J.

doi:10.1016/j.healun.2019.08.018

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…We observed that 5 sessions over 1 week resulted in a mean MFI reduction higher than 80% for all preformed DSA in our series. This finding is consistent with the study from Edwards et al 8 who considered an efficient desensitization response when a 25% reduction in the MFI is obtained for 90% of the strongest positive antibodies.…”

Section: Discussionsupporting

confidence: 93%

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Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Guihaire

D'Avino

Stéphan

et al. 2020

Clinical Transplantation

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Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16–70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow‐up was 25 months [20–32]. Mean fluorescence intensity (MFI) of HLA‐specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1–74] and 6.8 [1–29] PP sessions were performed per patient before transplant. The mean number of HLA‐specific antibodies before HT was 9.6 for score 6 [4–13] and 5.8 for score 8 [1–12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79–100] for Class I and 44.2% for Class II [0–83]. Hospital survival was 100%, and early antibody‐mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.

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Section: Discussionsupporting

confidence: 93%

“…from Edwards et al8 who considered an efficient desensitization TA B L E 2 a Any DSA with MFI > 1000.…”

mentioning

confidence: 99%

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Guihaire

D'Avino

Stéphan

et al. 2020

Clinical Transplantation

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“…Although there have been no randomized controlled trials of i.v. Ig for desensitization in HT candidates, there is evidence of decreased anti-HLA antibodies with subsequent successful transplantation in left ventricular assist device (LVAD) recipients (2-4) [32][33][34]. i.v.…”

Section: Management Of the Sensitized Patientmentioning

confidence: 99%

Management of the sensitized heart transplant candidate

Kittleson

2023

Current Opinion in Organ Transplantation

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Purpose of review For sensitized heart transplant candidates who have antibodies to human leukocyte antigens (HLA), finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting heart transplantation has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. Recent findings Advances in the assessment of HLA antibodies allow for identification of heart transplant candidates who may benefit from desensitization strategies to widen the donor pool and mitigate the risk of adverse posttransplant outcomes. Summary Antibody sensitization is a barrier to successful heart transplantation and strategies to identify sensitized patients, stratify their risk, and mitigate this risk through desensitization is crucial to optimize the quality of life and survival of HT recipients.

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“…In a study of 13 sensitized children awaiting heart transplantation, 77% of sensitized patients defined by C1q-single antigen bead (SAB) PRA >18% were successfully desensitized with IVIG and transplanted with 100% 1-year survival ( 101 ). Similarly, in 13 children with homograft repair, those receiving higher cumulative doses of IVIG were more likely to respond to treatment although longer follow-up time was a confounding factor ( 60 ). IVIG has also been used to desensitize LVAD recipients with newly elevated CDC PRAs after implant.…”

Section: Current Approaches To Desensitization In Heart Transplantationmentioning

confidence: 99%

“…Given that many such patients may be turned down for transplant, the true scope of the problem is likely underestimated. Whether children, with perhaps greater immune plasticity and a shorter duration of exposure, respond differently is difficult to parse out (60)(61)(62).…”

Section: Congenital Heart Diseasementioning

confidence: 99%

Current Desensitization Strategies in Heart Transplantation

Habal

2021

Front. Immunol.

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Heart transplant candidates sensitized to HLA antigens wait longer for transplant, are at increased risk of dying while waiting, and may not be listed at all. The increasing prevalence of HLA sensitization and limitations of current desensitization strategies underscore the urgent need for a more effective approach. In addition to pregnancy, prior transplant, and transfusions, patients with end-stage heart failure are burdened with unique factors placing them at risk for HLA sensitization. These include homograft material used for congenital heart disease repair and left ventricular assist devices (LVADs). Moreover, these risks are often stacked, forming a seemingly insurmountable barrier in some cases. While desensitization protocols are typically implemented uniformly, irrespective of the mode of sensitization, the heterogeneity in success and post-transplant outcomes argues for a more tailored approach. Achieving this will require progress in our understanding of the immunobiology underlying the innate and adaptive immune response to these varied allosensitizing exposures. Further attention to B cell activation, memory, and plasma cell differentiation is required to establish methods that durably abrogate the anti-HLA antibody response before and after transplant. The contribution of non-HLA antibodies to the net state of sensitization and the potential implications for graft longevity also remain to be comprehensively defined. The aim of this review is to first bring forth select issues unique to the sensitized heart transplant candidate. The current literature on desensitization in heart transplantation will then be summarized providing context within the immune response. Building on this, newer approaches with therapeutic potential will be discussed emphasizing the importance of not only addressing the short-term pathogenic consequences of circulating HLA antibodies, but also the need to modulate alloimmune memory.

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

Cited by 7 publications

References 22 publications

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Management of the sensitized heart transplant candidate

Current Desensitization Strategies in Heart Transplantation

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