With antibody levels that preclude the majority of potential organ matches, highly sensitized transplant patients face long waitlist times, increasing the risk of morbidity and mortality before a suitable match is found. Although adult patients have established protocols for reducing antibody levels, the smaller pediatric population lacks the same level of standardization.

“In pediatrics, we personalize treatment based on the patient,” says pediatric cardiologist Erin V. Shea, MD, director of pediatric heart failure and cardiomyopathy at Duke Health. “Anything we can do to safely get our patients to transplant in a reasonable amount of time with minimal complications has better outcomes for our patients and gives us greater access to organs.

“Any time there is heart dysfunction and you’re worried about the patient long term, we’re happy to see them on a consult basis or collaborate in their care, whether that’s to optimize heart failure care or get them onto the transplant waitlist before they’re deconditioned,” Shea continues.

Adapting desensitization protocols depends on the specific antibodies and pathways the patient is sensitized to. Immunosuppression, infection, and cancer risks also influence treatment plans. Potential treatments include plasmapheresis/plasma exchange (PLEX) to remove antibodies and intravenous immunoglobulin (IVIg) to replace antibodies.

“This potentially creates a feedback loop to ideally decrease production,” says Shea. “Then we give at least one medication that targets the immune system and production of antibodies.” These treatments include monoclonal antibody infusions such as:

• Bortezumib
• Daratumumab, which targets CD38 on plasma cells
• Eculizumab for a complement-mediated pathway
• Tocilizumab

“We may use one immunomodulating medication if the patient has a lot of antibodies and plasma cells, but their immune system is relatively quiescent,” Shea adds. “Or, if the patient has a lot of plasma cells and antibodies and their immune system is active, we may target different immune system pathways with multiple immunomodulating medications.”

The organ to be transplanted also influences the protocol. “Liver transplants can actually cross many types of antibodies and do reasonably well,” Shea explains. “But the small intestine has a lot more immunogenic cells, so it’s harder to desensitize with a meaningful long-term outcome.”

Rather than eliminating antibodies, desensitization aims to lower antibodies to levels where patients are better able to find a match, Shea says. Treatments continue during the initial period post-transplant but may not be necessary long term, depending on the immune response post-transplant.

Across all organs, Duke’s multidisciplinary teams provide world-class care to transplant patients and advance transplant science, continually widening the donor pool. “At Duke, we are willing to take on higher-risk transplants, knowing that there are different therapies we can try for sensitization, but also knowing that we have ways to get organs, ideally sooner, that are a good match for our patients, to let them live a longer life,” Shea concludes.