Stanford Pediatricians Transplant Kidneys Without the Need for Immunosuppressive Drugs | News Center

Researchers working with adult patients, including a team at Stanford University, have performed continuous transplants of stem cells and kidneys from living donors. When the donors were half-matched, they were partially successful, but patients were unable to completely discontinue the immunosuppressive drug after transplantation, or in other trials not conducted at Stanford, severe GVHD. The risk was unacceptably high.

The Stanford University Pediatrics team has introduced improvements that significantly improve the success of the combination of the two transplants and significantly reduce the risk. Their key innovation is a change in the way donor stem cells are processed.

After the stem cells have been removed from the donor’s body, the technician performs a depletion of alpha-beta T cells. This eliminates the type of immune cells that cause GVHD. Bertaina’s team showed that depletion of alpha beta T cells, developed while working in Italy before coming to Stanford University, makes stem cell transplants safer and allows for genetically half-matched transplants. I did.The protocol is relatively gentle and safe for children Immune disorder People who are medically too vulnerable to traditional stem cell transplants. Alpha beta T cells recover 60-90 days after the patient. In other words, it regains full immune function.

When a Stanford Children’s Health doctor began taking care of several children with very rare immune disorders Schimke Immune Bone Dysplasia (SIOD)They found that a multi-step approach could meet the patient’s medical needs.

“SIOD includes chronic kidney disease that ultimately requires a kidney transplant,” says Bertaina. SIOD also causes bone marrow failure. That is, patients need stem cell transplants to provide a healthy new immune system.

“These were unique patients who had to do stem cell and kidney transplants,” Bertaina said.

Medical pioneer

Each of the three children in the new scientific report received a stem cell transplant incorporating alpha-beta T cell depletion from one of their parents. After 5-10 months, after recovering from a stem cell transplant, each child received a kidney from the same parent who donated the stem cells.

One patient had a mild episode of graft-versus-host disease that affected the skin, which was resolved with medication. After the kidney transplant, doctors gave the first two patients immunosuppressive drugs for 30 days and then discontinued the drug. The third patient experienced short-term side effects from immunosuppression, including hyperglycemia. In that case, the medication was discontinued earlier.

All three patients no longer have an immune disorder. They have lived for 22 to 34 months without immune disorders and with the new fully functional kidneys that their bodies have accepted.

“They are doing everything. They go to school, go on vacation, play sports,” Bertena said. “They are living a completely normal life.”

Kruz and Paizlee, who recently completed their first year this summer, are excited about swimming lessons, day camps, and family camp trailer trips. According to Jessica Davenport, these activities were not possible before the transplant.

“They are walking miracles,” Davenport said. “It’s really great that they are paving the way for other families to experience the same things we have experienced.”

Currently, the team is expanding the protocol to more types of patients. This includes children who received the first kidney transplant that the body rejected. This group includes up to half of the children who have had a kidney transplant. In these cases, it is beneficial to replace the immune system before the transplant, as the patient’s own immune system becomes hypersensitive and is likely to attack the transplanted second kidney.

The new FDA approval targets several diseases that cause renal damage, including SIOD, cystinosis, systemic lupus erythematosus, and loss of previous kidney transplants due to focal segmental glomerulosclerosis. In these conditions, if the immune problem is not resolved prior to the kidney transplant, the immune disorder can attack the newly transplanted kidney. DISOT is an alternative that can help resolve a patient’s immune system and keep new kidneys healthy, Bertaina said.

She said that adults whose body refused the first kidney transplant or who had an immune disorder that attacked the kidneys could receive DISOT in the future.

The team is also planning to investigate how their approach can be adapted to other solid organ transplants, including those from deceased donors.

“It’s a challenge, but it’s not impossible,” Bertena said. “It takes three to five years of research to make it work.”

This research was supported by funding from Kruzn for the Kure Foundation.