Bone Marrow Transplants: Treating a Spectrum of Diseases

by Food and Drug Administration (FDA)

When Judge Morris was diagnosed with leukemia 10 years ago, doctors told him he would need a bone marrow transplant to survive.

"It gave me hope for a cure, but the big question was whether I'd ever find the right donor," says Morris, 47. The odds of finding a marrow donor in the general population are typically 1 in 20,000. Because of a rare genetic makeup, Morris' odds were 1 in a million.

For the next four and a half years, the Tulsa, Okla., resident underwent chemotherapy treatments and waited. He prepared his family for the possibility that he might not be around to see his two children grow up. "Then an angel named Mike Giglio came into our lives," Morris says. The National Marrow Donor Program found Giglio through its network, and Morris received a bone marrow transplant from Giglio in March of 1993.

"The leukemia is gone, I'm off medication, and not a night goes by that I don't thank Mike for saving my life," Morris says. At seven years post-transplant, the chance that the leukemia will return, experts say, is less than 5 percent.

Each year, bone marrow transplants give patients a chance to beat diseases once believed to have no cure. Although the first successful bone marrow transplant didn't take place until 1968, the discovery of human leukocyte antigens (HLA) in 1958 was a major breakthrough because it allowed recipients to be matched with donors.

Since then, the procedure has steadily advanced as research uncovered ways to improve transplant techniques. Donor registries have grown significantly and drugs that prevent rejection and infection have improved. The Food and Drug Administration reviews new drugs used to prepare patients for bone marrow transplants, and drugs that aid in recovery. The FDA also reviews so-called growth factors, genetically engineered substances that stimulate growth of the transplanted cells.

Treating a Spectrum of Diseases

Bone marrow, a jelly-like substance in the cavities of our bones, contains hematopoietic (blood-forming) stem cells, commonly referred to as simply "stem cells." These cells are critical for life because they continually produce red blood cells, which carry oxygen; white blood cells, which help fight infections; and platelets, which act as clotting agents to stop bleeding.

Bone marrow transplants may help cure diseases that interfere with the production of any of these types of cells. These include cancers such as leukemia, Hodgkin's disease and other lymphomas. For Judge Morris and others with chronic myelogenous leukemia (CML), a common form of leukemia, abnormal white blood cells fill up the bone marrow, enter the bloodstream, and can invade organs and tissues. Transplants also may help patients with non-cancerous conditions characterized by a deficiency in blood cell production, such as aplastic anemia and inherited immune disorders.

Diseases of blood-making cells in the marrow are hard to cure because traditional treatment — chemotherapy or radiation — destroys not only abnormal cells, but also normal cells. A bone marrow transplant allows doctors to treat patients with high-dose therapy — effectively killing all the cells in the bone marrow — and then replace the damaged marrow with healthy marrow. Craig Mullen, M.D., a member of the pediatric bone marrow team at the University of Texas M. D. Anderson Cancer Center, likens the situation to having a weed in your garden. "You have to kill it, but in doing so, you'll kill the other plants around it," he says. "The only way to get a new garden is to plant new seeds and repopulate it."

In earlier years, transplants were more commonly performed in the late stages of disease. But the 1970s marked a shift toward performing transplants during remission from disease, a change that improved patient outcomes.

Doctors have also used bone marrow transplants in experimental treatments of patients with solid tumor cancers (breast and testicular, for example) that require aggressive treatment with high doses of toxic drugs. Transplants are used to try to "rescue" the patient from the high doses of chemotherapy needed to destroy the cancer, which also destroys the marrow. Werner Bezwoda, Ph.D., a South African researcher, gave the scientific community and cancer patients hope for this experimental procedure through his studies of breast cancer patients. Dating back to 1990, the studies showed an overall survival advantage for high-dose chemotherapy and transplant in women with breast cancer and stimulated a wide acceptance of this treatment. But in February 2000, Bezwoda's work was discredited after an external audit and his own admission to falsifying data. Many scientists, however, think the procedure may still have merit. "You can't rule the treatment out just because we didn't find evidence of it working in limited trials," says Grant Williams, M.D., an oncologist in FDA's Center for Drug Evaluation and Research. "We need further data before we can know whether it works or not."

Two Types of Transplants

Transplants usually are categorized as allogeneic or autologous. Allogeneic transplants use bone marrow cells from another person who is genetically similar. The transplant is called syngeneic if the donor is an identical twin, which makes for a perfect match. Autologous transplants, the most common type, use the patient's own cells, which are removed, frozen, and reinjected later. In 1998, there were approximately 37,000 autologous bone marrow transplants and 17,000 allogeneic transplants worldwide, according to the International Bone Marrow Transplant Registry.

FDA reviews devices used in the collection, processing, purging and storage of stem cell products. In July 1999, FDA approved two cell separation devices that can select stem cells and decrease the number of cancerous cells that may be inadvertently re-infused into a transplanted recipient. "With autologous transplants (in which a patient uses his or her own stem cells), there may be tumor cells circulating in the bone marrow or blood that we don't want to give back," explains Stephen Litwin, M.D., a medical officer in FDA's Center for Biologics Evaluation and Research. Cell separation devices allow doctors to separate healthy stem cells from tumor cells. Litwin notes that the long-term benefits of this tumor "purging" have not been proven in clinical trials.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.