Pediatric heart transplantation across a positive crossmatch: First year results from the CTOTC-04 multi-institutional study

Abstract

Sensitization is common in pediatric heart transplant candidates and waitlist mortality is high. Transplantation across a positive crossmatch may reduce wait time, but is considered high risk. We prospectively recruited consecutive candidates at eight North American centers. At transplantation, subjects were categorized as nonsensitized or sensitized (presence of ≥1 HLA antibody with MFI ≥1000 using single antigen beads). Sensitized subjects were further classified as complement-dependent cytotoxicity crossmatch (CDC-crossmatch) positive or negative and as donor-specific antibodies (DSA) positive or negative. Immunosuppression was standardized. CDC-crossmatch-positive subjects also received perioperative antibody removal, maintenance corticosteroids, and intravenous immunoglobulin. The primary endpoint was the 1 year incidence rate of a composite of death, retransplantation, or rejection with hemodynamic compromise. 317 subjects were screened, 290 enrolled and 240 transplanted (51 with pretransplant DSA, 11 with positive CDC-crossmatch). The incidence rates of the primary endpoint did not differ statistically between groups; nonsensitized 6.7% (CI: 2.7%, 13.3%), sensitized crossmatch positive 18.2% (CI: 2.3%, 51.8%), sensitized crossmatch negative 10.7% (CI: 5.7%, 18.0%), P = .2354. The primary endpoint also did not differ by DSA status. Freedom from antibody-mediated and cellular rejection was lower in the crossmatch positive group and/or in the presence of DSA. Follow-up will determine if acceptable outcomes can be achieved long-term.

Use of the terminal complement inhibitor eculizumab in paediatric heart transplant recipients

“…18 More recently, Webber et al reported a higher incidence of a composite outcome (death, re-transplant, and haemodynamically significant rejection) in recipients with a positive crossmatch heart transplant (18.2%). 19 This observation when compared to the composite outcome of 10.7% in the negative XM group was not statistically significant probably due to the small sample size. These results give hope to the feasibility of transplant across a positive crossmatch for select patients, especially when a better defined antibody-mediated rejection treatment regimen can be formulated as several small studies in the adult renal transplant population have reported promising results in the treatment of antibody-mediated rejection with eculizumab.…”

Incidence, characterization, and impact of newly detected donor-specific anti-HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC-04 study

“…The cardiac consortium of the NIAID/NIH-sponsored Clinical Trials in Organ Transplantation in Children (CTOTC) program (www.ctotc.org) was developed to explore the impact of alloantibodies on pre- and post-transplant outcomes in pediatric heart candidates, with a focus on the management of the highly sensitized candidate including those with a positive donor-specific cytotoxicity crossmatch. 17,18 Study design, candidate sensitization status, risk factors for sensitization and primary outcomes from CTOTC-04 are described elsewhere in this volume. 17,18 CTOTC-04 also provides a unique opportunity to study the clinical importance of ndDSA in the first year after pediatric heart transplantation.…”

“…17,18 Study design, candidate sensitization status, risk factors for sensitization and primary outcomes from CTOTC-04 are described elsewhere in this volume. 17,18 CTOTC-04 also provides a unique opportunity to study the clinical importance of ndDSA in the first year after pediatric heart transplantation.…”

Variability in donor selection among pediatric heart transplant providers: Results from an international survey

“…This has led to differing strategies in the approach to highly sensitized patients, including protocols for antibody depletion following transplantation across a positive XM as well as efforts aimed toward desensitization in the pretransplant period . Recent data from the CTOTC‐04 multi‐institutional study demonstrated that patients transplanted across a positive XM have a greater incidence of cellular and antibody‐mediated rejection, but no difference in the cumulative end‐point of death, retransplantation, or rejection with hemodynamic compromise at 1‐year follow‐up . Data from our survey clearly demonstrate that there is no consensus in the approach to patients who are highly sensitized.…”

“…[36][37][38] Recent data from the CTOTC-04 multi-institutional study demonstrated that patients transplanted across a positive XM have a greater incidence of cellular and antibody-mediated rejection, but no difference in the cumulative end-point of death, retransplantation, or rejection with hemodynamic compromise at 1-year follow-up. 39 Data from our survey clearly demonstrate that there is no consensus in the approach to patients who are highly sensitized. There was near perfect equipoise in the utilization of prospective crossmatching and in the willingness to transplant across a positive virtual XM, irrespective of desensitization strategy.…”