In a DFCI lab, lead technologist Wendy Haskell (right) handles a bag of precious stem cells with Jerome Ritz, MD, director of the Cell Manipulation Core Facility.
Bone marrow basics
Transplants are used to treat diseases of the bone marrow — leukemia, lymphoma, multiple myeloma, and certain noncancerous conditions — as well as some solid tumors, usually after other treatments have failed. There are two basic types of transplants: autologous, in which a patient's own tissue is extracted, or harvested, and re-implanted after the patient undergoes high-dose radiation and chemotherapy; and allogeneic, where tissue comes from a carefully matched donor (often, a family member) before being infused into the patient.
The essence of the transplant procedure are cells known as hematopoietic stem cells. Like a slab of clay on a potter's wheel that can be molded into a variety of objects, they give rise to all the cells in blood and lymph: red blood cells that carry oxygen, white blood cells that fight disease, and platelets needed for clotting. The spongy marrow inside bones contains especially high concentrations of stem cells, making it a natural target for transplant.
More recently, doctors have found ways of raising the number of stem cells in circulating, or "peripheral," blood with medication, enabling them to harvest sufficient quantities relatively easily. At Dana-Farber today, about 90 percent of all transplants involve stem cells taken from peripheral blood rather than from bone marrow.
"The early results from our trials are very exciting. We have been looking for ways to reduce transplant-related side effects for many years, and these data tell us we are on the right track."
— Joseph Antin, MD
Refinements over the past three decades have made stem cell transplants safer and more reliable, but this slowly improving record doesn't diminish the fact that they remain risky. The high doses of radiation and chemotherapy that precede transplantation can cause mouth sores, nausea, diarrhea, rashes, hair loss, lung and liver disorders, and other problems. The procedure itself can bring on infection and organ damage and requires weeks of patient isolation afterward to avoid germs.
The most notorious problem associated with allogeneic transplants is graft-versus-host disease (GVHD). This occurs when immune-system cells in donated tissue recognize their new host as foreign and attack his or her organs and tissues. The result can range from relatively mild problems, such as minor itching, to life-threatening disorders including liver failure. A variety of drugs can reduce GVHD, but they also have side effects.
GVHD can be thought of as the dark twin of the graft-versus-leukemia effect. The same family of immune cells, known as T lymphocytes, that pursue and kill leukemia and lymphoma cells also target patients' healthy cells and tissues. One of the main challenges facing researchers is to find ways of intensifying the GVL effect while alleviating GVHD.
- Next: An immune booster
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