Allo-Antibodies in Pediatric Heart Transplantation

There is currently a renewed interest in allo-antibodies in transplantation. In 1966,
Kissmeyer and colleagues reported that pre-existing antibodies directed against donor cells
could cause hyperacute rejection of the renal allograft. Three years later, in a landmark
study, Patel and Terasaki showed that a lymphocytotoxic assay to identify donor-specific
antibodies was highly predictive of acute graft failure. These observations led to the
practice of performing prospective, donor-specific cross-matches by lymphocytotoxicity assay
for all kidney transplants and for heart and lung transplants when the candidate has a
positive panel reactive antibody (PRA) assay. A concept evolved that transplantations should
not be performed across a positive cytotoxicity cross-match. The purpose of this study is to
determine the clinical outcomes of sensitized pediatric heart transplant recipients with a
positive donor-specific cytotoxicity cross-match and to compare them with outcomes in
nonsensitized heart transplant recipients.

This study will enroll 370 pediatric heart transplant recipients over a period of 3 years.
The follow-up period will last up to 3 years. All participants will be enrolled
pretransplant. In the pretransplant phase, visits will occur every 6 months. These routine
visits will continue until transplant or the end of the study. They will coincide with
routine pretransplant status visits. At the time of transplant, the participants will be
assigned to one of two groups. Group A will include participants who are allo-antibody
negative (less than 10% by AHG CDC-PRA and ELISA in all DTT-treated serum samples). Cohort B
will include participants who have the presence of a DTT-treated AHG CDC-PRA of greater than
or equal to 10% and/or an ELISA-PRA greater than or equal to 10% in any pretransplant
sample.

Both cohorts will receive standard transplantation care. This study has no interventions.
All participants will undergo regular blood tests, and, those in the sensitized group will
have additional blood testing performed after the transplant and lasting until the end of
the study. Post-transplant visits will occur while participants are recovering in the
hospital; at Months 1, 3, and 6; and annually until the study closes.

The information collected for the study include data from a physical exam, routine testing,
adverse (AEs) and serious adverse (SAEs) events assessments, and blood collection. Each time
a biopsy is done, the study will ask to review the biopsy tissue and to collect a sample. If
stored tissue is not available, none will be collected.

Inclusion Criteria:

- All participants listed for heart transplantation at participating CTOT-C study
sites.

Exclusion Criteria:

- Listed for multiple organ transplant

- Inability or unwillingness of the participant or parent/guardian to give written
informed consent or comply with the study protocol

- Condition or characteristic which in the opinion of the investigator makes the
participant unlikely to complete at least one year of follow-up

- Current participation in other research studies that would, or might, interfere with
the scientific integrity or safety of current study (e.g. by interference with
immunosuppression management guidelines, study endpoints, excessive blood draws or
SAE evaluation).