Research in context
Evidence before this study
We searched PubMed and Web of Science using the search terms “ABO”, “blood group”, “incompatible”, “heart”, “transplantation”, “children”, “pediatric”, “polysaccharide”, “immune response”, “B-cell”, “immature immune system”, “outcomes”, “rejection”, and “graft vasculopathy” for all articles from database inception until Aug 31, 2020, with no language restrictions. This search was supplemented with authors' knowledge of the field. Over the past 10 years, ABO-incompatible listing has been progressively adopted for children younger than 2 years. The first multicentre experience of ABO-incompatible heart transplantation with detailed clinical outcomes on 55 children was published in 2013, and there have been several registry analyses starting in 2009 with smaller numbers (the largest including 90 patients). Outcomes were mostly limited to survival and freedom from rejection in the first year after transplantation, showing non-inferior outcomes to ABO-compatible transplantation. Very little data on infectious diseases after ABO-incompatible heart transplantation are available, with one study suggesting overall longer freedom from any infection for ABO-incompatible recipients. Two studies previously showed a potential benefit for ABO-incompatible transplants in regard to HLA immune response and one previous registry study suggested lower rejection rates in the first year compared with ABO-compatible transplantation. Alterations of the immune system might provide an immunological benefit or increased vulnerability to pathogens requiring polysaccharide-directed immune response, such as encapsulated bacteria.
Added value of this study
To our knowledge, our study cohort is more than triple the largest previously assessed cohort. We compared key post-transplantation outcomes between patients who received ABO-incompatible and ABO-compatible heart transplants, using propensity score matching to account for key predictors of clinical outcomes. Besides confirming similar long-term survival in the two groups, this study also provides granular data on secondary outcomes such as rejection, graft vasculopathy, post-transplant lymphoproliferative disorder and, for the first time, timing and frequency of severe infections. A specific look at infections with encapsulated bacteria in the context of the altered polysaccharide immune response after ABO-incompatible heart transplantation has revealed that, in contradiction to the original hypothesis, ABO-incompatible patients have less frequent infections with later occurrence after transplantation. Controlling for clinical characteristics and transplantation era also shows that the previously described lower frequency of rejection might not be independently associated with ABO-incompatible transplantation but is due to confounders.
Implications of all the available evidence
ABO-incompatible heart transplantation for young children is a clinically safe approach that allows children faster access to donor organs at no additional risk or disadvantage to post-transplantation survival, frequency of rejection, graft vasculopathy, or tumours. There might be a benefit, rather than added risk, in regard to infections when compared with ABO-compatible transplantation. Our findings should encourage centres and transplant jurisdictions still hesitant to embrace ABO-incompatible heart transplantation to implement this option to benefit more patients. Future studies should explore the possible expansion of ABO-incompatible transplantation to young children requiring other organ transplants, older children awaiting heart transplant, and possibly even adults.