Regression of advanced kidney cancer seen with allogeneic stem cell transplantation

September 13, 2000

Researchers at the National Institutes of Health (NIH) report that advanced kidney cancer, a disease notoriously resistant to therapy and usually fatal, can be completely or partially reversed in some patients with the use of blood stem cell transplants from a healthy sibling donor. Using this investigational approach, substantial and occasionally complete regression of widespread tumors was observed in the majority of 19 patients with treatment-resistant metastatic renal cell carcinoma who were treated at the National Heart, Lung, and Blood Institute (NHLBI) Stem Cell Transplant unit. This Phase I/II study appears in the Sept. 14, 2000, issue of the New England Journal of Medicine.

Principal investigator and lead author of the paper, Richard Childs, M.D., of NHLBI's Hematology Branch said, "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 two years from the initiation of therapy." According to Childs, the overall response rate of greater than 50 percent in patients with treatment-resistant disease is remarkable, considering that current first-line therapy is effective in less than 20 percent of cases. Three patients (16 percent) had total regression of all metastases and seven (38 percent) showed partial regression of disease.

Although tumor regressions, described by the authors as "dramatic," occurred in a number of patients, Childs cautioned that significant, but rarely fatal, complications were associated with the procedure. "It should therefore remain an investigational approach to treating kidney cancer at this point in time," he said.

Advanced renal cell carcinoma is usually fatal in less than a year. Although highly resistant to chemotherapy treatment, renal cell carcinoma is unusual among solid tumors in that it is susceptible to attack from the body's own immune system. The use of drugs designed to boost immune cells, such as interleukin-2 and interferon-alpha, has provided benefit to some patients, although many do not to respond to such therapy. Since potent immune-mediated anticancer effects have been observed against blood-borne cancers such as leukemia and lymphoma following conventional allogeneic stem cell transplantation, a pilot trial was initiated by investigators from the NHLBI in collaboration with scientists from The National Cancer Institute (NCI) and the NIH Warren Grant Magnuson Clinical Center to explore similar beneficial antitumor effects in patients with treatment-resistant kidney cancer.

The treatment approach used in this study was based on prior laboratory research which showed that immune cells taken from a healthy donor are capable of generating powerful antitumor effects against a number of different solid tumors. Between February 1998 and August 1999, researchers enrolled 19 patients with widespread metastatic kidney cancer who did not respond to prior therapy. To make the procedure safer, a modified transplant regimen was developed which used low-intensity conditioning to spare patients the multiple toxicities associated with conventional high-dose allogeneic transplantation. A combination of two immunosuppressive drugs, cyclophosphamide and fludarabine, was given with the intent to knock out the patient's immune system to allow the foreign donor immune cells to take hold. Blood stem cells and lymphocytes from a tissue-matched sibling donor were then infused. The drug cyclosporine was administered to prevent rejection of the donor cells and graft vs. host disease, a potentially life-threatening complication that occurs when donor immune cells attack the patient's normal tissues.

Once the transplant had taken place, patients were rapidly tapered off cyclosporine to enable the donor immune cells to become more effective and to increase the chances of generating an antitumor effect. Patients who failed to completely replace their immune system with donor cells or who had tumor growth following the procedure received additional infusions of donor lymphocyte cells to enhance antitumor reaction.

Response to treatment was defined as complete if all measurable tumor disappeared and partial if measurable lesions decreased in size by at least 50 percent for at least 30 days. Regression was seen in multiple sites, including lymph nodes, adrenal glands, liver, bones, and lung. A unique pattern of cancer regression was observed, characterized by delayed tumor regressions that did not occur until a median of four months following transplantation. In some cases tumor regression was markedly delayed, occurring greater than seven months following the procedure in two patients. Tumor regressions did not occur until the patient's immune system had been completely replaced by the donor's cells, and, in most cases, followed the withdrawal of cyclosporine. The researchers noted that, interestingly, six of 10 patients who ultimately had a response to the therapy had initial evidence of tumor growth in the first few months after transplantation.

The procedure was not without complications. Acute graft vs. host disease, usually mild to moderate in severity, was the major toxicity, occurring in 53 percent of the patients. Two patients died due to transplant-related complications, one from graft vs. host disease and one from a complication of bacterial sepsis.

Two patients who showed a response to the therapy have since developed progressive disease. Although follow-up was relatively short, there was a trend toward a survival advantage in those patients who had tumor shrinkage following the procedure. According to W. Marston Linehan, M.D., of the Urologic Oncology Branch of the NCI, "We hope to expand the number of patients who can enroll in our clinical trial. The ultimate objective is to test this therapy in a large, randomized controlled trial to determine the true efficacy of this treatment."
-end-
For more information about cancer, visit NCI's Web site at http://www.cancer.gov. Information on clinical research conducted by NHLBI's Hematology Branch can be found at http://www.nhlbi.nih.gov

NCI Press Office
(301) 496-6641


NIH/National Heart, Lung and Blood Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.