A dual immune/solid organ transplant procedure has been successfully used to perform kidney transplantation without the need for long-term immunosuppressive therapy in three children with a rare genetic disorder, according to a brief report in The New England Journal of Medicine (1). The study was led by Alice Bertaina, MD, PhD, of the Division of Stem Cell Transplantation and Regenerative Medicine and associate professor of pediatrics at Stanford University.
The patients were three children (two siblings) with Schimke immuno-osseous dysplasia (SIOD), an autosomal recessive disease associated with short stature due to bone dysplasia, glucocorticoid-resistant nephrotic syndrome, and T cell immunodeficiency. All underwent αβ T cell-depleted and CD19 B cell-depleted hematopoietic stem cell transplantation from haploidentical parents. This regimen has been successfully used in patients with nonmalignant diseases with low rates of acute and chronic graft-versus-host disease and transplant-related death.
After the children had received confirmation of immune reconstitution, they received living-donor kidney transplants from the same parental donors. Peri-transplant immunosuppressive drugs were given to reduce reperfusion-related inflammation, but the drugs were tapered off within 30 days, after which, the children received no further immunosuppression.
Follow-up studies confirmed successful engraftment, with full donor and myeloid chimerism. At up to 34 months after transplantation, the transplant recipients had normal kidney function with no evidence of rejection. In vitro studies showed that circulating donor-derived T cells had functional tolerance to the transplanted kidney alloantigens and thus were potentially unable to mediate graft rejection.
As noted in a press release from Stanford Medicine (2), the dual immune/solid organ transplant procedure has received US Food and Drug Administration approval for use in SIOD and several other diseases causing kidney damage. The researchers plan further studies evaluating the protocol for other patients in need of kidney transplantation and for other types of solid organ transplants.
References
- 1.↑
Bertaina A, et al. Sequential stem cell–kidney transplantation in Schimke immuno-osseous dysplasia. N Engl J Med 2022; 386:2295–2302. doi: 10.1056/NEJMoa2117028
- 2.↑
Digitale E. Stanford pediatricians transplant kidneys without need for immune-suppressing drugs. Stanford Medicine. June 15, 2022. https://med.stanford.edu/news/all-news/2022/06/kidney-transplant-without-immunosuppressants.html
