Impact of age on incidence and prevalence of moderate-to-severe cellular rejection detected by routine surveillance biopsy in pediatric heart transplantation

Background The effect of age at transplant on rejection detected by routine surveillance biopsy (RSB) in pediatric heart transplant (HT) recipients is unknown. We hypothesized there would be low diagnostic yield and decreased prevalence of rejection detected on RSB in infants (age <1 year) when compared with children (age 1 to 9 years) and adolescents (age 10 to 18 years). Methods We utilized Pediatric Heart Transplant Study (PHTS) data from 2010 to 2013 to analyze moderate-to-severe (ISHLT Grade 2R/3R) cellular rejection (MSR) detected only on RSB (RSBMSR). Results RSB detected 280 of 343 (81.6%) episodes of MSR. RSBMSR was detected in all age groups even >5 years after HT. Infant RSBMSR had a greater proportion (p = 0.0025) occurring >5 years after HT (39.2 vs 18.4 vs 10.8%) and a lower proportion (p = 0.0009) occurring in the first year after HT (25.5 vs 60.6 vs 51.7%) compared with children and adolescents, respectively. Freedom from RSBMSR was 87 ± 7% in infants, 76 ± 6% in children and 73 ± 7% in adolescents 4 years after HT. In 1-year survivors who had RSBMSR in the first year after HT, the risk of RSBMSR occurring in Years 2 to 4 was significantly (p < 0.0001) greater than patients without RSBMSR in the first year (hazard ratio 21.28, 95% confidence interval 10.87 to 41.66), regardless of recipient age. Conclusions RSBMSR exists in all age groups after pediatric HT with long-term follow-up. The prevalence in infant recipients is highest >5 years after HT. Those with RSBMSR in the first year after HT are at a high risk for recurrent rejection regardless of age at HT.