Pathological antibody‐mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes

Hollander, Seth A.; Peng, David M.; Mills, Marcos; Berry, Gerald J.; Fedrigo, Marny; McElhinney, Doff B.; Almond, Christopher S.; Rosenthal, David N.

doi:10.1111/petr.13197

Cited by 10 publications

(6 citation statements)

References 25 publications

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“…It is conceivable that increased biopsy frequency in the earlier era may have led to more detection of clinically silent rejection of unclear consequence. The significance of an ISHLT grade 2R or greater biopsy on morbidity and mortality is uncertain, though evidence suggests it may be predictive of later morbidity and mortality 18‐21 . Third, as mentioned above, our ability to risk‐stratify patients into high and low rejection risk may be limited.…”

Section: Discussionmentioning

confidence: 99%

Impact of induction strategy change on first‐year rejection in pediatric heart transplantation at a single center—From postoperative basiliximab to either postoperative anti‐thymocyte globulin or preoperative basiliximab

Sisson

Padilla

Hubbard

et al. 2021

Clinical Transplantation

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Background Our pediatric heart transplant center transitioned from post‐bypass basiliximab (BAS) induction to either anti‐thymocyte globulin (ATG) or pre‐bypass BAS. The purpose of this study was to compare first‐year rejection rates before and after this change. Methods A single‐center retrospective analysis was conducted of pediatric heart transplant recipients from 2010 to 2019. Primary outcome was first‐year rejection. Bivariate analysis, Kaplan‐Meier curves, and multivariable regression were performed across eras. Results Forty‐three early era patients (55%) received post‐bypass BAS, and 35 late era patients (45%) received pre‐bypass BAS (n = 17) or ATG (n = 18). First‐year rejection decreased in the late era (31% vs 53%, p = .05). This finding was more pronounced after excluding infants (38% vs 73%, p = .006). Late era was associated with a decreased likelihood of rejection (all cohort OR 0.19, 95% CI 0.05‐0.66; infants excluded OR 0.17, 95% CI 0.04‐0.61). No differences in post‐transplant lymphoproliferative disease, donor‐specific antibody, or infection were observed. Conclusions Fewer late era patients receiving ATG or pre‐bypass BAS induction had first‐year rejection compared to the early era patients receiving standard post‐bypass BAS induction. This programmatic shift in induction strategy was readily achievable and potentially effective in reducing first‐year rejection.

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Section: Discussionmentioning

confidence: 99%

Impact of induction strategy change on first‐year rejection in pediatric heart transplantation at a single center—From postoperative basiliximab to either postoperative anti‐thymocyte globulin or preoperative basiliximab

Sisson

Padilla

Hubbard

et al. 2021

Clinical Transplantation

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“…The impact of anti-human leucocyte antigen (HLA) donor-specific antibodies (DSAs) on graft survival and graft function in kidney and heart transplantation is crucial[ 1 - 3 ]. However, their impact on liver transplantation (LT) is still controversial: Some research suggests that the overall impact on graft and patient outcome is limited[ 4 ], but other studies found that it may be an independent risk factor for patient death and graft loss[ 5 - 7 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

Schotters¹,

Beime²,

Briem-Richter³

et al. 2021

WJH

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BACKGROUND In a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort. AIM To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients. METHODS We performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication. RESULTS DSA-positive pediatric patients showed a higher prevalence of chronic rejection ( P = 0.01), fibrosis ( P < 0.001) and re-transplantation ( P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development. CONCLUSION DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.

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“…We elected to not include AMR in our analysis since much of our data predates standard AMR pathologic classifications. However, we have recently reported our center's recent AMR outcomes which demonstrated an exceedingly low incidence of ≥pAMR 2 biopsies . Especially for patients in whom long‐term routine biopsy is likely low yield, noninvasive methods of surveillance for vasculopathy and graft function deserve further study and consideration…”

Section: Discussionmentioning

confidence: 99%

Long‐term surveillance biopsy: Is it necessary after pediatric heart transplant?

Peng

Ding

Hollander

et al. 2018

Pediatric Transplantation

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Due to limited and conflicting data in pediatric patients, long‐term routine surveillance endomyocardial biopsy (RSB) in pediatric heart transplant (HT) remains controversial. We sought to characterize the rate of positive RSB and determine factors associated with RSB‐detected rejection. Records of patients transplanted at a single institution from 1995 to 2015 with >2 year of post‐HT biopsy data were reviewed for RSB‐detected rejections occurring >2 year post‐HT. We illustrated the trajectory of significant rejections (ISHLT Grade ≥3A/2R) among total RSB performed over time and used multivariable logistic regression to model the association between time and risk of rejection. We estimated Kaplan‐Meier freedom from rejection rates by patient characteristics and used the log‐rank test to assess differences in rejection probabilities. We identified the best‐fitting Cox proportional hazards regression model. In 140 patients, 86% did not have any episodes of significant RSB‐detected rejection >2 year post‐HT. The overall empirical rate of RSB‐detected rejection >2 year post‐HT was 2.9/100 patient‐years. The percentage of rejection among 815 RSB was 2.6% and remained stable over time. Years since transplant remained unassociated with rejection risk after adjusting for patient characteristics (OR = 0.98; 95% CI 0.78‐1.23; P = 0.86). Older age at HT was the only factor that remained significantly associated with risk of RSB‐detected rejection under multivariable Cox analysis (P = 0.008). Most pediatric patients did not have RSB‐detected rejection beyond 2 years post‐HT, and the majority of those who did were older at time of HT. Indiscriminate long‐term RSB in pediatric heart transplant should be reconsidered given the low rate of detected rejection.

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Pathological antibody‐mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes

Cited by 10 publications

References 25 publications

Impact of induction strategy change on first‐year rejection in pediatric heart transplantation at a single center—From postoperative basiliximab to either postoperative anti‐thymocyte globulin or preoperative basiliximab

Impact of induction strategy change on first‐year rejection in pediatric heart transplantation at a single center—From postoperative basiliximab to either postoperative anti‐thymocyte globulin or preoperative basiliximab

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

Long‐term surveillance biopsy: Is it necessary after pediatric heart transplant?

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