Scientist triumphs after setback in kidney transplant method

By Patricia Wen
Globe Staff / January 24, 2008
Dr. David H. Sachs was full of optimism when the third patient in his $1 million study was wheeled into the recovery room at Massachusetts General Hospital after an experimental kidney transplant.
graphic Kidney donations
graphic Research team's approach
The first two patients had thrived, adding credibility to an unorthodox idea that Sachs had pioneered over his career, that transplanting a donor's bone marrow along with the kidney could solve the problem of organ rejection, sparing patients a lifetime of powerful antirejection drugs.
But 10 days after the third patient's surgery, Sachs's phone rang at his spacious lab overlooking Boston Harbor. A colleague reported that William Andrews, a 43-year-old father of two, was rejecting the kidney.
Sachs and his research team remember the darkness of the ensuing months in 2003, when they abruptly suspended their transplants for nearly two years. Andrews was demoralized and on dialysis, his sister's donated kidney seemingly wasted. Over and over, Sachs paced the corridors of his lab asking himself, "What did we miss?"
Today, capping a comeback from the crisis, Sachs and his team are reporting that they unraveled the explanation for Andrews's rejection. After they tweaked their protocol, adding a drug to avert what happened to Andrews, two new patients have thrived without the long-term need for antirejection drugs, according to a paper published in the New England Journal of Medicine.
Overall, four of Sachs's five patients have experienced no organ rejection, a particularly striking accomplishment because they all received kidneys that were different from their own tissue type. Transplants of such mismatched organs are the most common and the most likely to be rejected, even when patients take immunosuppressive drugs.
"I had confidence we would figure it out," said the 66-year-old Harvard Medical School professor, who has dedicated more than three decades to conquering organ rejection. He said the results restored his faith that his once-radical idea will eventually become mainstream, making organ transplants safer and more available.
Transplant surgeons said Sachs's study represents a pivotal moment in organ transplantation, demonstrating that it is feasible to eliminate immunosuppressive drugs with their debilitating side effects, such as skin warts, cataracts, and increased risks of heart disease, diabetes, and serious infections. If the results are borne out in a larger group of patients, the Mass. General technique has the potential to help transplant recipients live longer. Within 10 years, half of all transplanted organs fail because of chronic rejection, a bleak predicament in this era of organ shortages.
"This is landmark work," said Dr. Joshua Miller, an organ transplant researcher at Northwestern University's Feinberg School of Medicine in Chicago.
Other researchers cautioned that only the healthiest patients may be able to endure the rigorous treatments, including chemotherapy and radiation, that precede the transplant. Continued...