Induction and Increased Risk of Infections in Pediatric Fontan Patients after Heart Transplantation

Abstract

<h3>Purpose</h3> To understand whether patients who have undergone Fontan palliation may have a higher susceptibility to post-HT infections given thymectomy in infancy and known depletions of T-cell subsets. <h3>Methods</h3> This was a single-center, retrospective cohort analysis of pediatric patients undergoing HT for dilated cardiomyopathy (DCM) or Fontan failure, who underwent induction with anti-thymoglobulin (ATG). The primary endpoint was infection in the first 180 days post-HT, defined as (1) positive blood/urine/respiratory culture; (2) positive viral PCR (excluding CMV and EBV); (3) skin or wound infection; and/or (4) culture-negative infection if a full antibiotic course (>5 days) was completed. Secondary endpoints included (1) absolute lymphocyte (ALC) and CD3 counts after 3 and 5 doses of anti-thymocyte gammaglobulin (ATG); (2) the incidence of post-transplant lymphoproliferative disorder (PTLD); and (3) rejection (≥ Grade 2R ACR or pAMR2) in the first 180 days post-HT. <h3>Results</h3> From 2014 to 2019, 59 pts (26 Fontan, 33 DCM) underwent HT at a median age of 14.7 (IQR 10.6, 19.5) and 11.7 (IQR 1.4, 13.6) years, respectively. The median total ATG received was 7.4 (IQR 4.9, 7.7) vs 7.5 (IQR 7.3, 7.6) mg/kg (p=NS). The median CD3 [8 (IQR 5, 14) vs 16 (IQR 10, 39); p=0.01] after 3 doses of ATG and ALC [172 (IQR 98, 400) vs 427 (IQR 205, 824); p=0.014] after 5 doses of ATG was lower in Fontan vs DCM patients (<b>A,B</b>). Twenty-three patients (39%) developed ≥1 infection within 180 days post-HT, with a higher rate of infection in Fontan patients (54% vs 27%, p=0.03; <b>C, D</b>). Adjusted for pre-transplant ALC, the risk for infection within 30 days post-HT for Fontan patients was OR 7.62, 95% CI 1.13-51.48, p=0.037. There was no difference in the incidence of PTLD (12% vs 0%; p=0.08) or rejection (12% vs 21%; p=0.49) between Fontan vs DCM patients. <h3>Conclusion</h3> Compared to DCM patients, Fontan patients have lower CD3 and ALC after induction, as well as a higher risk of infection. Modifications to induction therapy for Fontan patients may be considered.