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Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow-up was 6.25 years. Unadjusted 5-year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8-19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: The objective of this study was to determine the association between the genetic polymorphisms of proinflammatory and regulatory cytokines and long-term rates of repeat and late acute rejection episodes in pediatric heart transplant (PHTx) recipients., Methods: Three hundred twenty-three PHTx recipients: 205 White non-Hispanic, 43 Black non-Hispanic, and 75 Hispanic were analyzed for time to first repeat and late acute rejection episodes by race, age at transplantation, and gene polymorphism (interleukin [IL]-6, -174 G/C, IL-10, -1082 G/A, -819 C/T, 592 C/A; vascular endothelial growth factor (VEGF) -2578 C/A, -460 C/T, +405 C/G; tumor necrosis factor alpha (TNF-alpha)-308 G/A)., Results: Recipient black race and older age at transplant were risk factors for both repeat and late rejections, though black race was more significantly related to late rejection (P=0.006). Individually, TNF-alpha high, IL-6 high, VEGF high, and IL-10 low phenotypes did not impact the risk of repeat or late rejection. However, the combination VEGF high/IL-6 high and IL-10 low was associated with increased estimated risk of late rejection (P=0.0004) and only marginally with repeat rejection (P=0.051). In a multivariate analysis, adjusting for age and race, VEGF high/IL-6 high and IL-10 low still remained an independent risk factor for late acute rejection (RR=1.91, P<0.001)., Conclusion: This is the largest multicenter study to document the impact of genetic polymorphism combinations on PHTx recipients' outcome. The high proinflammatory (VEGF high/IL-6 high) and lower regulatory (IL-10 low) cytokine gene polymorphism profile exhibited increased risk for late rejection, irrespective of age and race/ethnicity.

Background: Post-transplant lymphoproliferative disorders (PTLD) are an important cause of morbidity and mortality after organ transplantation. We sought to better define the prevalence, pathology, current therapeutic approaches, and outcomes of PTLD in a large group of children who had received heart transplants., Methods: We assessed data on patients followed up at 19 centres in the Pediatric Heart Transplant Study (PHTS) from 1993 to 2002. Probability of freedom from PTLD was assessed along with details of presentation, pathology, treatment, and outcomes. Risk factors for survival and event-free survival were investigated., Findings: Of 1184 primary transplant recipients, 56 (5%) developed PTLD. Probability of freedom from PTLD was 98% at 1 year, 94% at 3 years, and 92% at 5 years. Mean time to PTLD was 23.8 months. Most common sites of disease were gastrointestinal tract (n=22, 39%) and respiratory system (n=14, 25%). Histology was polymorphic in 35 (65%) and monomorphic in 19 (35%). 47 of 48 cases were of B-cell origin, 39 of 45 (87%) were Epstein-Barr virus positive. Probability of survival was 75% at 1 year, 68% at 3 years, and 67% at 5 years after diagnosis. Death from graft loss was as frequent as death from PTLD., Interpretation: About 5% of paediatric heart-transplant recipients develop PTLD, almost always of B-cell lineage and driven by Epstein-Barr virus. Although many achieve satisfactory outcomes, mortality remains substantial with death due to progressive disease and allograft loss. Advances in management should focus on strategies to protect the allograft as well as improved therapies for PTLD.

Background: Detailed information regarding the spectrum and predictors of infection after heart transplantation in children is limited because of relatively small numbers of patients at any single institution. We therefore used combined data obtained from the Pediatric Heart Transplant Study Group to gain additional information regarding infectious complications in the pediatric population., Methods: To determine the time-related risk of infection and death related to infection in a large pediatric patient population, we analyzed data related to 332 pediatric patients (undergoing heart transplantation between January 1, 1993, and December 31, 1994) from 22 institutions in the Pediatric Heart Transplant Study Group., Results: Among the 332 total patients, 276 infections were identified in 136 patients. Of those patients with development of infection, a single infection episode was reported in 54% of patients, 21% had two infections, and 25% had three or more infections. Of the 276 infections, 164 (60%) were bacterial, 51 (18%) were due to cytomegalovirus, 35 (13%) were other viral (noncytomegalovirus) infections, 19 (7%) were fungal, and 7 (2%) were protozoal. Bacterial infections were more common in infants younger than 6 months of age at time of transplantation, comprising 73% of all infections as compared with 49% in patients older than 6 months of age. The incidence of bacterial infection peaked during the first month after transplantation, with the actuarial likelihood of a bacterial infection among all patients reaching 25% at 2 months. The most common sites of bacterial infection were blood and lung (74% of bacterial infections). Cytomegalovirus accounted for 59% of viral infections, with a peak hazard occurring at 2 months after transplantation. Among all infections, cytomegalovirus was less common in infants younger than 6 months of age (8% of all infections) than in older patients (25%). By multivariate analysis, risk factors for early infection included younger recipient age (p = 0.05), mechanical ventilation at time of transplantation (p = 0.0002), positive donor cytomegalovirus serologic study result with negative recipient result (p = 0.004), and longer donor ischemic time (p = 0.04). The overall mortality rate from infection was 5%, with an actuarial freedom from death related to infection of 92% at 1 year after transplantation. The mortality rate was high in patients with fungal infections (52%), yet was low for those with cytomegalovirus infection (6%). Infections accounted for 27% of the overall mortality rate in infants younger than 6 months of age, compared with 16% for older patients., Conclusions: Although most infections in pediatric heart transplant recipients are successfully treated, infection remains an important cause of posttransplantation morbidity and death, especially in infants. Bacterial infections predominate within the first month after transplantation, whereas the peak hazard for viral infections occurs approximately 2 months after transplantation. Cytomegalovirus infections are common in the pediatric transplant population, but death related to cytomegalovirus is low.