Differences in Baseline Immunophenotype in Pediatric Cardiac Transplant Evaluation: How Informed Reductions in Immunosuppression can Improve Patient Outcomes

Abstract

Lifelong multi-drug immunosuppression is essential in pediatric cardiac transplant with regimens varying between pediatric centers. Current data suggests pre-transplant immunologic phenotype differences may predispose patients to over-immunosuppression. At our tertiary care center, targeted reduction of immunosuppression has recently become common practice despite limited published data. We hypothesize that individualized reduction of immunosuppression in pediatric cardiac transplant patients based on baseline immunophenotype will lead to improved outcomes post-transplant.From January 2020 through July 2022, 52 pediatric patients were referred to our tertiary care center for cardiac transplant evaluation, which includes Immunology evaluation. Patient demographics, cardiac history, and pre-transplant immune evaluation (T/B/NK cell quantitation, quantitative immunoglobulins, vaccine responses and T cell functional testing, as available) were collected. Genetic testing was reviewed. 28 patients who completed cardiac transplant were followed up to 12 months for information on reduced immunosuppression (decreased/bypassed induction with antithymocyte globulin and/or decreased long-term immunosuppression goals), infections, and rejection post-transplant.Of patients referred for evaluation, 63% had congenital heart disease (CHD). Nearly 100% of CHD patients required cardiac surgery in the first year of life with thymectomy. Of all referred patients and of those with available total T cell count (CD3+ T cells), 54% were lymphopenic (CD3+ T cells < 1000/mm3), and 11% of the lymphopenic children were severely lymphopenic (CD3+ T cells < 300/mm3). Patient IgG levels outside of protein losing enteropathy (PLE) and vaccine responses were within normal limits. Available microarray results showed 5 children with abnormal chromosomal syndromes (including 22q11.2 deletion syndrome). Of those referred, 28 patients underwent cardiac transplant and review of outcomes for up to 12 months post-transplant is on-going.Immunologic abnormalities are inconsistent in cardiac patients and may be secondary to early thymectomy, PLE or chromosomal deletion syndromes. Our data demonstrates significant differences in pre-transplant immunologic phenotypes and will add to the limited literature on decreasing immunosuppression in severely lymphopenic cardiac patients. This retrospective study provides encouragement for partnership between immunology and cardiology teams to conduct larger, prospective multicenter studies to further understand individualization of immunosuppression regimens, the role of baseline immunophenotyping to inform these decisions and the resulting improvement in transplant outcomes.