Study Offers New Hope For Infants Awaiting Heart Transplantation

Newborns requiring heart transplantation often die because of the critical shortage of donor hearts. Efficient allocation of the rarely available organs is hampered by the presumed need for a recipient who is ABO-compatible with the donor. Babies with blood group O encounter disproportionate competition for organs, whereas organs from donors with the less common B and AB blood types may go unused if there is no recipient of appropriate size and compatible blood type on the waiting list.

In the study, 10 infants between the ages of four hours and 14 months received heart transplants from donors of incompatible blood type between 1996 and 2000. The overall survival of the recipients of ABO-incompatible donor hearts was 80 per cent. The two children that died, died of causes unrelated to ABO-compatibility. The children who received ABO-incompatible transplants had no more rejection or chronic problems after transplantation than the recipients with ABO-compatible donor hearts. The expanded donor pool afforded by this protocol contributed to a decrease in waiting list deaths from 58 to seven per cent.

"We reasoned that because the infant immune system is immature and lacks the antibodies that cause hyperacute rejection, it would be safe to cross the blood group barrier. In adults, blood type compatibility in heart transplantation is crucial because the recipient's immune system is fully developed and equipped with high levels of antibodies that will cause immediate rejection of the donated heart if it is not of compatible blood-type," said Dr. Lori West, the lead author of the study, and a cardiologist and transplant immunologist at The Hospital for Sick Children.

"What's really exciting about this research is that we seem to have induced tolerance in these babies to the donor blood group antigens. No other case or clinical situation has been reported of human neonatal transplant tolerance. This tells us that the window of susceptibility to tolerance induction in humans, at least to certain antigens, likely extends into the newborn period and isn't just restricted to fetal immune development," added Dr. West, also an assistant professor in the Department of Paediatrics at the University of Toronto.

"This group of children is not freed from the need for lifelong immunosuppressive drug therapy to prevent rejection, because there are many additional antigens in the transplanted heart that trigger a rejection response. However, this study has important implications not only for expansion of the donor pool, but for the future development of tolerance-inducing protocols for young children requiring organ transplantation, particularly those diagnosed in utero with lethal diseases. Tolerance is much more likely to be successfully induced during immaturity than any time later in life," said Dr. West.