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CD34+ Selection Removes Tumor Cells Why do some patients relapse following high-dose chemotherapy and an autologous stem cell transplant? The answer is not clear, but researchers are investigating whether a technique called CD34+ selection (CD 34 positive selection) can reduce the risk of relapse following an autologous transplant for patients with certain diseases. An Autologous Transplant In an autologous stem cell transplant, the patient is given high doses of chemotherapy, with our without radiation, to destroy the disease. The high-dose chemotherapy also destroys the stem cells in the patient’s bone marrow that are responsible for producing all of the body’s blood cells. Without a healthy supply of blood cells, the patient will die. To rescue patients from this lethal side effect of treatment, stem cells are collected or “harvested” from patients before they receive high-dose chemotherapy. The healthy stem cells are stored, and later re-infused into the patient after high-dose chemotherapy has ended. Studies have shown that the stem cells collected from some patients with breast cancer, multiple myeloma and lymphoma prior to high-dose chemotherapy also contain tumor cells. Some researchers have reported a correlation between the presence of tumor cells in harvested bone marrow and the likelihood of relapse following an autologous transplant. This has prompted investigators to study different techniques for removing tumor cells from harvested bone marrow and stem cells. Removing the Tumor Cells One technique under investigation is called CD34+ selection. Stem cells have a special marker on their surface called the CD34 antigen. Some tumor cells, such as lymphoma cells, breast cancer cells, and multiple myeloma cells do not normally have this antigen on their surface. By passing the stem cell sample through a device called a cell separator, doctors can capture or “select” cells with the CD34 antigen on magnetic beads or gels, and wash away the remaining cells in the sample. Several studies have demonstrated that CD34+ selection is effective in reducing the number of tumor cells in the stem cell sample harvested from patients with multiple myeloma, breast cancer and lymphoma. Whether this translates into prolonged survival is still being investigated. “Investigators are also looking at the possibility of combining CD34+ selection with ‘negative selection’ of tumor cells,” says Ken Cornetta MD of the Indiana Cancer Research Institute. Negative selection, also known as purging, is a process that uses either chemicals or monoclonal antibodies – special proteins that can distinguish between normal cells and tumor cells - to kill cancer cells in the stem cell sample. “By combining these two techniques, it may be possible to increase the efficacy of tumor removal,” says Cornetta. Other Applications Research involving CD34+ selection is not limited to patients with cancer. Studies are underway to determine whether patients with autoimmune disorders such as rheumatoid arthritis, systemic lupus, erythematosis, scleroderma and multiple sclerosis may also benefit from CD34+ selection. “With autoimmune diseases, the goal is to restart the immune system,” explains Richard Burt MD, Director of Hematopoietic Cell Transplantation, Northwestern University Medical School. “CD34+ selection enables us to separate defective immune cells from stem cells that can generate a healthy immune system for the patient.” Early results with this technique have varied, depending on the disease, but look promising, he says. Researchers at the National Institutes of Health (NIH) are attempting to combine CD34+ selection with gene therapy to treat patients with an inherited blood disorder called chronic granulomatous disease (CGD). Patients with CGD have defective neutrophils (a type of white blood cell) that cannot produce superoxide or hydrogen peroxide needed to fight bacterial and fungal infections. “Stem cells are collected from patients and purified using CD34+ selection,” says Harry Malech MD, who heads the research effort. “They are then incubated with a special virus that can transfer a gene into the stem cells that is missing from the patient’s neutrophils. When the stem cells are reinfused into the patient, they generate neutrophils that can produce superoxide and hydrogen peroxide.” Although scientifically exciting, the process is still very inefficient and currently unable to cure patients, says Malech. “Our goal is to build on and improve this technique.” A similar technique has been used successfully by French researchers to treat patients with X-linked severe combined immune deficiency syndrome (SCIDS), he says. Malech’s group is also exploring the possibility of using an allogeneic stem cell transplant to treat patients with CGD. Using CD34+ selected stem cells that have been further manipulated to remove T-cells—a type of white blood cell that can cause graft-versus-host-disease—Malech and his colleagues have managed to generate a normal immune system in eight of ten patients treated thus far. “We’re very excited about this program,” he says. It may even be possible to use the CD34 negative cells to develop an anti-tumor vaccine, speculates Norbert Gorin MD of Johns Hopkins Oncology Center. “Eventually most modern therapeutic strategies to fight cancer will probably rely in one way or another on this type of new technology." |
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