Physicians at Stanford Medicine have developed a way to provide pediatric kidney transplants without immune-suppressing drugs. Their key innovation is a safe method to transplant the donor's immune system to the patient before surgeons implant the kidney.
The medical team has named the two-transplant combination a "dual immune/solid organ transplant," or DISOT. A scientific paper describing the first three DISOT cases, all performed at Lucile Packard Children's Hospital Stanford, published online June 15 in the New England Journal of Medicine. The journal also ran an editorial about the research.
The Stanford innovation removes the possibility that the recipient will experience immune rejection of their transplanted organ. (Organ rejection is the most common reason for a second organ transplant.) The new procedure also rids recipients of the substantial side effects of a lifetime of immune-suppressing medications, including increased risks for cancer, diabetes, infections and high blood pressure.
Safely freeing patients from lifelong immunosuppression after a kidney transplant is possible."
Alice Bertaina, MD, PhD, report's lead author, associate professor of pediatrics, Stanford
The senior author of the report is David Lewis, MD, professor of pediatrics at Stanford.
The first three DISOT patients were children with a rare immune disease, but the team is expanding the types of patients who could benefit. The protocol received FDA approval on May 27, 2022, for treating patients with a variety of conditions that affect the kidneys. Bertaina anticipates that the protocol will eventually be available to many people needing kidney transplants, starting with children and young adults, and later expanding to older adults. The researchers also plan to investigate DISOT's utility for other types of solid-organ transplants.
The scientific innovation from Bertaina's team has another important benefit: It enables safe transplantation between a donor and recipient whose immune systems are genetically half-matched, meaning children can receive stem cell and kidney donations from a parent.
The advance is especially meaningful for Jessica and Kyle Davenport of Muscle Shoals, Alabama. Their two children, both born with a rare and potentially deadly immune disease, are among the first recipients of DISOT: 8-year-old Kruz received transplants from Jessica, while his 7-year-old sister, Paizlee, received transplants from Kyle.
"They've healed and recovered, and are doing things we never thought would be possible," said Jessica Davenport. After years of helping Kruz and Paizlee cope with severe immune deficiency — and high infection risk — as well as kidney dialysis, she and her husband are thrilled that their children have more normal lives.
The idea of transplanting a patient with their organ donor's immune system has been around for decades, but it has been difficult to implement. Transplants of stem cells from bone marrow provide the patient with a genetically new immune system, as some of the bone marrow stem cells mature into immune cells in the blood. First developed for people with blood cancers, stem cell transplants carry the risk of the new immune cells attacking the recipient's body, a complication called graft-versus-host disease. Severe GVHD can be fatal.
Spitzer, T.R., et al. (2022) Transplantation Tolerance through Hematopoietic Chimerism. New England Journal of Medicine. doi.org/10.1056/NEJMe2204651.