Stem cell transplant from a healthy sibling donor reverses advanced kidney cancer in some patients, study finds.

Advanced kidney cancer, a disease notoriously resistant to therapy and usually fatal within a year, can be completely or partially reversed in some patients by stem cell transplantation from a healthy sibling donor, according to a report in the September 14th issue of the New England Journal of Medicine.

Metastatic cancer regressed in 10 (53%) of the 19 patients treated in the Phase I/II study-3 patients (16%) had a complete response, and 7 (38%) had a partial response. All of the study subjects had previously failed other treatments for their renal cell cancer.

"Considering that there are no current treatments that benefit patients who have not responded to conventional therapy, we are very encouraged by the early high response rate in our first group of patients treated, with a few patients remaining completely free of cancer more than 2 years from the initiation of therapy," said Richard Childs, MD and coresearchers at the National Heart, Lung, and Blood Institute.

Although highly resistant to chemotherapy, renal cancer is rare among solid tumors in its susceptibility to attack by the body's immune system. The use of drugs designed to boost immune function such as interleukin-2 and interferon-alpha has provided benefit to some patients, but many do not respond. Since potent immune-mediated anticancer effects have been observed against leukemia and lymphoma following conventional allogeneic stem cell transplantation, the investigators speculated that the procedure might produce similar antitumor effects in patients with treatment-resistant kidney cancer.

Following their stem cell transplants, the patients were rapidly tapered off cyclosporine to enable the donor immune cells to function more effectively, thus increasing the chances of generating an anticancer effect. Patients who failed to completely replace their immune system with donor cells, or who had tumor growth following their transplants, received additional infusions of donor lymphocyte cells to promote antitumor activity. Tumor regression did not occur until the immune system had been completely replaced by the donor cells and, in most cases, developed only after the withdrawal of cyclosporine. Interestingly, the researchers noted that 6 of 10 patients who ultimately had a favorable response had initial evidence of tumor growth in the first few posttransplant months.

Stem cell transplantation was not without complications, however. Acute graft-versus-host disease (GVHD), usually mild to moderate in severity, was the major toxicity, occurring in 53% of the patients. Two patients died due to transplant-related complications, one from GVHD, and one from bacterial sepsis. And 2 patients who showed a response to the therapy have since developed progressive disease.

In addition to these complications, "an equally important limitation [to transplant] is the prolonged time required for the induction of an antitumor effect," the authors wrote. "Patients with rapidly advancing metastatic disease, who would be unlikely to live long enough for the generation of a graft-versus-tumor effect, would not benefit from such therapy."

Although the study was small and the follow-up relatively short, the researchers said there was a trend toward a survival advantage in those patients who had tumor shrinkage following the procedure. Eventually, they hope to test the therapy in large, randomized controlled trials to determine its true efficacy.