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Transplant breakthrough could free patients from a lifetime on anti-rejection drugs
By CLAIRE BATES
Patients who receive donor organs must take dozens of pills every day to stop their bodies from rejecting them, even if they are a close match. Now scientists have developed a technique that has allowed kidney transplant patients to come off immunosuppressant drugs without damaging their new organs.
The breakthrough treatment, created at Stanford University, targets radiation on a patient’s lymph nodes to weaken their immune system. The patient is then injected with stem cells drawn from the donor’s blood. When their immune system recovers it appears to be far more ‘friendly’ to the new organ. ‘It casts a blind eye on the foreign tissue of the graft,’ lead scientist Dr Samuel Strober said. The method has so far been tested on 12 patients suffering from kidney failure who had matching donor organs from close relatives. It follows more than 30 years of research on mice.
Dr Strober said: ‘Nobody has had any evidence of rejection, and the patients have been observed for at least a year and as long as three-and-a-half years and things have remained quiet. ‘Left to itself, the patient’s immune system would relentlessly attack a new organ unless it came from an identical twin. To stave off this attack, all transplant recipients are routinely placed on a regimen of immune-suppressing drugs. ‘Transplant recipients can ordinarily expect to be on a regimen of two or three immune-system-suppressing drugs for the rest of their lives,’ immunologist Dr Strober said.
While they help ward off rejection of the new organ by the patient’s own immune system, these drugs carry their own risk of side effects, such as high blood pressure, diabetes and cancer.‘ In addition to their potential side effects, these drugs all too often fail to prevent organ rejection. ‘In those cases, the patient experiences a gradual deterioration of the donated organ until it eventually fails, necessitating another transplant operation or a lifetime on dialysis.‘ Dialysis – which is the mechanical filtration of the blood – leaves patients immobilised for several hours three times a week, while a transplant holds the prospect of returning to a normal lifestyle.
There are an estimated 20,000 people on dialysis in England for kidney failure and nearly 400,000 in the U.S. Co-author Professor John Scandling said: ‘On average, transplant recipients have twice the life expectancy of people on chronic dialysis.’
A transplanted kidney from a living donor can last 25 years with conventional treatment. It is hoped that this new technique will extend life-expectancy far further. While the next technique costs up to $40,000 (£25,000) it has the potential to pay for itself with a few years, as failure of a transplanted kidney costs the healthcare system around $80,000 (£50,000). Under the protocol, the kidney recipient receives radiation treatment and injections of antibodies while still in the hospital a few days after surgery, and additional radiation doses over the next several days on an outpatient basis.
About 10 days after surgery, the recipient gets an injection of cells taken from the organ donor. All patients initially are put on two of the same immune-suppressing drugs (plus antivirals and antibiotics) that transplantation patients would normally get. After a month, one of the drugs is withdrawn; and the Stanford team monitors the patients, including the mixing of donor and recipient immune cells. If that mixing seems in balance six months after surgery, the recipient’s second immunosuppressant-drug dose is discontinued. If the mixing hasn’t been achieved, the patient remains on the drugs until it is.
The researchers reported on their progress in a letter published in the New England Journal of Medicine. The withdrawal of drugs from the first enrolled patient in the study was reported in the same journal in 2008. The researchers will now enrol patients who are set to receive imperfectly matched donor organs.
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