Ingenious technology leads to children receiving kidney transplants without immunosuppression

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Ingenious technology leads to children receiving kidney transplants without immunosuppression

Organ transplants can literally save lives, but they also come with conditions—often including lifelong immunosuppressive drug treatments needed to keep the immune system in check so it doesn’t reject the transplanted organ as a foreign invader.

Now scientists are reporting three successful kidney-to-organ transplants performed in children in California without the need for immunosuppression. The transplants used a new method that minimizes the risk of the new kidney being rejected.

That means freedom from immunosuppressants and their associated side effects, which aren’t always pleasant (and include an increased risk of cancer and diabetes). It also reduces the likelihood of needing a second transplant due to rejection of the first.

“It’s possible to safely recover from a lifetime of immunosuppression in kidney transplant patients,” said Alice Bertaina, associate professor of pediatrics at Stanford University in California.

The innovative technique works by safely transplanting the donor’s immune system into the patient – via stem cells derived from the bone marrow – before the kidney also proceeds: dual immune/solid organ transplantation, or DISOT. This has been attempted before, but with limited success.

An additional process has been added here. The researchers performed alpha-beta T-cell and CD19 B-cell depletion, which meant removing the types of immune cells that cause graft-versus-host disease, or GVHD — a potentially deadly complication that threatened to develop when similar techniques had been used in the past.

With a reduced risk of GVHD, the process was much safer. The removal of the alpha-beta T-cells is relatively “gentle”, making it suitable for medically vulnerable children, and it allows for genetically semi-matched transplants (from one parent). The removed cells naturally recover in the patient in 60-90 days and rebuild the immune system.

Other improvements have been made, including a reduction in the toxicity of chemotherapy and radiation treatment required prior to transplantation. However, some fairly strenuous preparatory work is required to turn off the patient’s immune system and prepare the body to accept a new organ.

The three children who received kidney transplants in this way suffer from an extremely rare genetic disease called Schimke’s immunoosseous dysplasia (SIOD), which reduces the body’s ability to fight off infection and can lead to kidney failure.

“This remarkable experience underscores the potential of combined or sequential hematopoietic stem cell transplantation and kidney transplantation to correct hematopoietic disorders and immunodeficiency and induce renal allograft tolerance,” write Thomas Spitzer and David Sachs of Massachusetts General Hospital in an accompanying editorial.

“SIOD is a rare disease associated with immunodeficiency, which undoubtedly contributed to the achievement of a successful donor HSCT transplant.”

While SIOD and all of its complications remain something to contend with, children are now all in possession of kidneys that are functioning as they should be. The researchers report that the transplants have been successful for at least 22 and 34 months.

“These were unique patients that we had to do a stem cell transplant and a kidney transplant on,” says Bertaina.

“They do everything: they go to school, they go on vacation, they play sports. They lead a completely normal life.”

The next steps are to expand the number of patients and the number of conditions this could work for, as so far it has only been demonstrated in patients with SIOD, making them particularly suitable for the procedure.

Of particular interest to the research team are patients who have already had a kidney transplant rejected by their body. This happens in up to half of all cases in children, resulting in a hypersensitized immune system that would most likely not accept a second kidney through a normal transplant procedure.

Children will benefit first, then researchers will work into old age. Eventually, the technique could even be adapted to cover transplants of organs other than kidneys, but it will take a while.

“It’s a challenge, but not impossible,” says Bertaina.

The research was published in New England Journal of Medicine.

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