The yield of surveillance endomyocardial biopsies as a screen for cellular rejection in pediatric heart transplant patients

Abstract

Endomyocardial biopsy is commonly used to screen for cellular rejection in pediatric heart transplant patients. The yield of EMBs when combined with newly developed immunohistochemical techniques and modern immunosuppression in pediatric heart transplant patients is unknown. After OHT, surveillance biopsies were performed on a routine basis on all pediatric patients. EMBs were also performed on symptomatic OHT patients suspected to have rejection. All positive results (greater than ISHLT grade 1B) were confirmed with immunohistochemical staining. A retrospective review of consecutive EMBs performed in this institution from January 1995 to January 2003 was performed. The echocardiographic results, clinical history and treatment changes at the time of every biopsy were also catalogued. Of the 1093 EMB results from 136 pediatric heart transplant grafts (127 patients, 64 male) reviewed, 825 biopsies were performed on patients managed with tacrolimus and 268 were performed on patients managed with cyclosporine. The patients managed with tacrolimus had an incidence of 0.85% (7/825) for significant rejection (greater than ISHLT grade 1B rejection) vs. an incidence of 4.1% (11/268) for the patients on cyclosporine (p < 0.0005). In the asymptomatic tacrolimus patients, only two screening biopsies (0.26%) manifest significant rejection, and both of these were performed within the first month after transplantation. Of the symptomatic tacrolimus patients, 9.1% (n = 5) had findings on biopsy consistent with significant cellular rejection. There were 25 patients with grade 1B rejection. Twenty-two of these patients were not treated, and all cases of grade 1B rejection resolved without clinical sequelae. For pediatric patients more than 30 days after OHT, EMB has failed to reveal significant episodes of cellular rejection in asymptomatic patients managed with tacrolimus.

Cost-effectiveness of Pediatric Heart Transplantation

“…Alternatively, many institutions employ tacrolimus, which may reduce the need for surveillance endomyocardial biopsies because of fewer rejection episodes. 20 Although the latter agent costs more, it has been suggested that the additional costs may be offset by fewer rejection episodes-although this argument is controversial. 21 Benchmarks are used to compare the cost-effectiveness of treatments.…”

Humoral Rejection in Pediatric Orthotopic Heart Transplantation

“…2 Despite this failure rate, the incidence of cellular rejection on endomyocardial biopsy (EMB) has been reported at only 0% to 8% for asymptomatic patients and 9% to 41% for symptomatic patients. 3,4 Furthermore, there is often no mention of humoral rejection (HR) in the literature on rejection episodes and development of transplant coronary artery disease (TCAD). 5,6 Data from the adult heart transplant literature suggest that HR is a significant cause of biopsy-negative, hemodynamically significant rejection episodes and graft failure.…”

The Impact of Age on the Incidence and Prevalence of Moderate to Severe Cellular Rejection Detected by Routine Surveillance Biopsy in Pediatric Heart Transplantation

“…Levi et al showed only a 0.36% incidence of EMB-positive rejection (ISHLT Grade ≥1B) in asymptomatic patients on tacrolimus therapy (770 biopsies) during the first year after transplant, and no asymptomatic patient had a positive biopsy at >1 year after transplant. 10 In contrast, other reports suggest RSB continues to detect late episodes of MSR. Kuhn et al reported an 8% to 10% annual incidence of moderate rejection up to 11 years after transplantation in a study including 269 children with a mean follow-up time of 5 years.…”

“…Previous single-center studies have shown a decreased incidence of positive surveillance biopsies (at least during the first year) in patients treated with tacrolimus compared with cyclosporine. 8,10 This study contained the expected limitations that accompany a retrospective database study. A significant amount of potential data were excluded due to lack of the main study variable.…”