New protocols expand donor pool for highly sensitized pediatric patients receiving heart transplants

March 31, 2022

Mayo Clinic Children's Center is using new protocols to expand the donor pool and improve outcomes for patients on the waitlist for pediatric heart transplant.

The pediatric heart transplant team is increasingly encountering highly sensitized pediatric heart transplant patients. Sensitization, defined as the presence of preformed antibodies against different human leukocyte antigens (HLAs), can occur due to prior cardiac surgeries, transfusion of blood products, mechanical support, homograft material, pregnancy or previous transplants.

The incidence of sensitization in pediatric heart transplant recipients is increasing, as many of these children have had surgical palliation prior to needing transplant. According to the International Society for Heart and Lung Transplantation's latest data report, nearly 25% of pediatric heart recipients are sensitized in the most recent era compared with only 6% of patients transplanted before 2000, and 55% have had prior cardiac surgery compared with 30% in the earlier era.

Sensitization matters because it:

Reduces the already limited donor pool
Increases wait times for transplant
Increases morbidity and mortality before transplant

Mortality rates for pediatric patients waiting for transplant range from 5% at large transplant centers to 30% at small transplant centers and may be even higher in sensitized patients.

"By using newer protocols with induction immunosuppression as well as strategies to remove the antibodies that could affect the new donor heart at the time of surgery and early after the transplant, we can use some donors that may have historically been contraindicated," says Rebecca K. Ameduri, M.D., a pediatric cardiologist. Dr. Ameduri, who has a wealth of experience in treating highly sensitized patients, recently joined Mayo Clinic Children's Center.

She continues: "With these protocols, children undergo induction immunosuppression as well as plasma exchange to remove circulating HLA antibodies prior to implanting donor hearts. The children then receive high doses of immunosuppression and continuing treatment with plasmapheresis for ongoing removal of donor-directed antibodies while they are inpatients early after the transplant.

"The post-transplant immunosuppression strategies are then determined by a multidisciplinary team that includes specialists in cardiac transplant surgery, pediatric transplant cardiology, transplant pharmacy, transplant immunology and pathology. All children undergoing heart transplant at Mayo Clinic have long-term follow-up with an experienced team of transplant specialists. Long-term follow-up is particularly important in high-risk transplants, as there may be concerns related to the induction immunosuppression regimen.

"With these aggressive strategies, sensitized patients have increased risk of early rejection but can do very well long term. The overall survival for pediatric heart transplant is very good in more-recent years, with one-year survival now at 92%."

Dr. Ameduri concludes: "An increasing body of research suggests that an intensive immunosuppression protocol is helpful in these higher-risk, highly sensitized patients. With our heart transplant program, we are offering children with a fatal disease an opportunity to live with a chronic disease and a reasonable quality of life. We do know that prior cardiac surgery and sensitization decrease the survival slightly. However, with this protocol, we can offer that opportunity to our higher risk patients who really have no other means of survival."