Stem Cell Transplant
From Kidney Cancer Resource
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Overview
As far as Kidney Cancer is concerned this is a very experimental treatment at this time.
2007.06.02 - Carole Buckley is one of the first people receiving this treatment in Britain which is being administered in Prof. Hawkins' department at Christies Hospital, Manchester for more details of this case see James Whale Fund/Forum
May we commend the articles at: Patient UK
& Also at: Cancerbackup
SCT for metastasized KC
Stem cell transplantation for metastasized kidney cancer
Findings by SBU Alert
Published: October 29, 2001 Version: 1
Technology and target group: Transplantation of blood-forming stem cells, where the donor is either a sibling or an unrelated person with matching tissue, is an established treatment method, eg, for malignant blood diseases. In the new host, stem cells are capable of restoring their bone marrow function and creating a functioning immune defense. Some donor cells are able to kill malignant cells via the so-called Graft-versus-Tumor (GvT) effect. By transplanting stem cells from a donor to a cancer patient, an attempt is made to initiate an immunologic reaction targeted at the tumor. To prevent rejection of the stem cells, transplantation is usually conducted following strongly immunoinhibiting pretreatment. This method is now being tested in patients with advanced kidney cancer. A condition for inclusion in the target group is that the patient must be in good general health. Since patients usually do not receive stem cells from an unrelated donor due to the increased transplantation-related risks, it is necessary for the patient to have a sibling donor. In Sweden, an estimated 150 patients per year are in the target group.
Patient benefits: Currently, small series of patients are being followed. There are no controlled studies that draw comparisons with conventional treatment methods, eg, palliative radiotherapy and immunotherapy. An American followup study of 19 patients with metastasized kidney cancer reported that approximately 40% had a partial or complete response following transplantation (ie, that at least half of the tumor mass had disappeared). It was reported that the tumor may grow during the initial period after transplantation when patients are treated with immunoinhibiting drugs. Preparatory treatment with chemotherapy and radiation may have side effects such as nausea, vomiting, and liver damage. The greatest transplantation-related risk is GvH (Graft-versus-Host) disease, which means an immunological attack on the patients healthy organs, mainly the skin, intestines, and liver. When a sibling with the same tissue type is the donor, the risks for severe GvH disease are estimated at 5% to 10%.
Scientific evidence: There is poor* scientific evidence concerning the short-term and long-term effects of the method. Since the effects are uncertain, no* estimation of the cost-effectiveness has been feasible.
Until further notice, stem cell transplantation for cancer should be considered an experimental treatment and should be provided only within the framework of scientific studies.
This summary is based on a report prepared at SBU in collaboration with Prof. Olle Ringdén MD PhD, Huddinge University Hospital and has been reviewed by Mats Brune MD PhD Sahlgrenska University Hospital. The full report is available only in Swedish (7 pages).
For Further Cross Referrence and the source of this article Click Here
Regression of Advanced aKC with SCT
Regression of Advanced Kidney Cancer Seen with Allogeneic Stem Cell Transplantation
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 (see the journal abstract).
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 carcinomais 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 lymphocytecells 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 versus 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.
To see the original of this article Click Here OR as initially released by NIH as a news release Click Here]
Comments
N.B. This article would seem to be based only on America & from September 2000 User: Greg L-W.
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