Organ transplants can actually save lives, but they also come with a price tag: a lifetime of immunosuppressive medicine treatments to keep the immune system in control, lest the donated organ be rejected as a foreign invader.
Scientists have now reported on three successful kidney organ transplants in youngsters in California that were performed without the use of immune suppression. The transplants were performed using a novel technique that reduces the chances of the new kidney being rejected.
This means no longer having to take immunosuppressants or deal with their unpleasant side effects (and include an increased risk of cancers and diabetes). It also lowers the likelihood of a second transplant being necessary owing to the first's rejection.
"Safely freeing patients from lifelong immunosuppression after a kidney transplant is possible," explains Alice Bertaina, an associate professor of pediatrics at Stanford University in California.
Dual immune/solid organ transplantation, or DISOT, is a new approach that successfully transplants the donor's immune system into the recipient - via stem cells from bone marrow – before the kidney is also transplanted. This has been attempted previously, but only with little success.
A new process was added in this case. The researchers utilized an alpha-beta T cell and CD19 B-cell depletion strategy, which means they removed the immune cells that cause graft-versus-host disease, or GVHD — a potentially fatal consequence that has been linked to similar procedures in the past.
The procedure was more safer since the risk of GVHD was decreased. The procedure for removing alpha-beta T cells is generally "soft," making it appropriate for medically susceptible infants, and it allows for genetically half-matched transplants (from a parent). The patient's immune system recovers spontaneously in 60-90 days after the cells are removed, and the patient's immune system is rebuilt.
Other changes included lowering the toxicity of the chemotherapy and radiation treatments that were necessary before to the transplant. Even so, some arduous preparation work is necessary to knock down the patient's immune system and prepare the body for receiving a new organ.
The three children who received kidney transplants in this fashion have Schimke immuno-osseous dysplasia (SIOD), a rare hereditary disorder that limits the body's capacity to fight 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 disorders of hematopoiesis and immunodeficiency and to induce tolerance of the kidney allograft," write Thomas Spitzer and David Sachs from Massachusetts General Hospital in an accompanying editorial.
"SIOD is a rare disorder that involves immunodeficiency, which undoubtedly contributed to the achievement of successful donor HSCT engraftment."
While the youngsters still have to contend with SIOD and its associated difficulties, they now all have healthy kidneys. According to the researchers, the transplants have been effective for at least 22 and 34 months.
"These were unique patients in which we had to do the stem cell transplant and a kidney transplant," Bertaina explains.
"They are doing everything: they go to school, they go on vacation, they are doing sports. They are having completely normal lives."
The next step is to broaden the number of individuals and diseases for whom this surgery may be effective, as it has only been proven in people with SIOD, who are well suited to the operation.
Patients who have already had a kidney transplant rejected by their body are of special interest to the study team. In children, this occurs in up to half of all instances, resulting in hypersensitized immune systems that are unlikely to accept a second kidney during a standard transplant surgery.
Children will be the first to benefit, with researchers working up to older ages after that. The approach might eventually be expanded to include organ transplants other than kidneys, but it will take time.
"That's a challenge, but it's not impossible," Bertaina admits.
