EMORY PHSYCIANS PERFORM THE FIRST, UNRELATED UMBILICAL CORD BLOOD TRANSPLANT FOR HIGH-RISK SICKLE CELL ANEMIA

In hopes of curing the blood disease that causes 12-year-old Keone Penn chronic pain and has already led to a stroke, Emory physicians performed the first, unrelated umbilical cord blood transplant for high-risk sickle cell anemia Dec. 11 in the AFLAC Cancer Center of Egleston Children¢s Hospital at Emory University.

In addition to the stroke that caused partial paralysis at the age of five, Keone has been repeatedly hospitalized (seven times in 1998 alone) and has experienced seizures and numerous infections. While Keone has required monthly transfusions to reduce his chances of having a second stroke, he was having significant problems tolerating the medication that kept the transfusions from causing his iron levels to become toxic.

"Conservatively speaking, there is a 50-50 chance that this first-in-the-world transplant will cure Keone," says Andrew M. Yeager, MD, professor of pediatrics and medicine at Emory University. Dr. Yeager is principal investigator of the clinical trial in which Keone, with the support of his mother, Leslie Penn, has volunteered to pioneer. "Unrelated umbilical cord blood transplantation is a reasonable option for a patient like Keone for whom a related or unrelated bone marrow donor does not currently exist."

Umbilical cord blood is a promising new source of stem cells, which are considered the "blood factories" within the body. Stem cells from the placenta and umbilical cord that would normally be discarded after the birth of a baby are collected once the mother's consent is obtained. The cells are kept frozen until they are transplanted, through intravenous injection, into the patient.

Success of a cord blood transplant can be compromised if: 1) the transplanted cord blood fights the body (called graft-versus-host disease)or vice versa (graft rejection); 2) the new cells die without taking hold; or 3) an infection overwhelms the patient. Emory physicians have stored some of Keone¢s own bone marrow, which was collected before he began intensive chemotherapy. This marrow will be given back to him if the cord blood cells do not take hold and produce normal blood cells.

Keone began intensive chemotherapy on Tuesday, Dec. 1, to kill the ineffective "blood factory" he now has and to suppress his immune system so the transplant will be better received.

Throughout the weeks after the transplant, Keone will be in isolation due to low blood counts. He will receive medications to suppress his immune response and lessen the chance of graft-versus-host disease and graft rejection. Keone also will receive blood transfusions to keep normal blood cells working in his body. During the first four weeks, Emory physicians expect to see the number of white blood cells (which fight infection) increase followed by increases in red blood cells (which carry oxygen) and then platelets (which help the blood to clot).

"If Keone's body shows signs of accepting the transplant during the first four weeks after transplant, we will be over one obstacle," explains Dr. Yeager. "Within three to six months, we should know whether the cord blood has enabled Keone's body to build a normal blood cell factory and replace the one that is now making sickled, red blood cells."

Emory physicians are basing their belief that this cord blood transplant may be successful on extensive international research, including studies at Emory and Egleston.

"In more than 100 children worldwide, bone marrow transplants from healthy siblings have been used to cure children with high-risk sickle cell anemia. Umbilical cord blood cell transplants from siblings or unrelated donors have cured other blood diseases and leukemia in children," Dr. Yeager says.

For more than 25 years, bone marrow transplantation has been an effective treatment for patients with leukemia, solid tumors and blood diseases. Initially, transplants were performed using marrow cells, which fill the cavities of the bones, from the patient¢s own body (called autologous transplantation) or from a relative with the same tissue type as the patient (called allogeneic transplantation).

Over time, research revealed that bone marrow and stem cells from unrelated, HLA-matched donors are also a good source for transplantation. For some patients, however, perfect tissue-type, or HLA, matches continue to be difficult to find through national and international volunteer donor registries. To address this problem, umbilical cord blood cell transplantation is the newest option.

An article in the Nov. 26, 1998, issue of The New England Journal of Medicine included data on most of the cord blood transplants from unrelated donors performed worldwide through January 1998. The study concluded that "placental blood transplants regularly engraft, cause graft-versus-host disease at a relatively low rate, and produce survival rates similar to those with transplantation of bone marrow from unrelated donors."

Like bone marrow, cord blood must be tested for how closely it matches the recipients six tissue-type, or HLA, antigens. Even though the match apparently does not have to be as close as it does for a bone marrow transplant, the better the match, the better the outcome. The best match for Keone was found in a cord blood unit at the New York Blood Center in New York, NY, the nation¢s largest cord blood bank.

"Because many African-Americans do not understand how important it is to become a donor, physicians were unable to find a bone marrow match for Keone," says Leslie Penn, Keone's mother. The Penns reside in Snellville, Ga. "We are very excited and optimistic about the cord blood procedure." In fact, her son is already planning ahead. "When I get better, I am going to play football," says the seventh grader.

The transplant was performed by Emory physicians at Egleston's AFLAC Cancer Center, the only group in the U.S. currently performing unrelated cord blood transplants in children with high-risk sickle cell anemia. As one of the largest pediatric oncology programs in the U.S., physicians at the AFLAC Cancer Center treat approximately 100 newly diagnosed childhood cancer patients each year. The AFLAC Center is part of ESR Children's Health System, Inc. ESR combines the strengths of Egleston Children's Health System and Scottish Rite Children's Medical Center, two well-established children's health systems based in Atlanta.

To date, Emory physicians have performed one adult and 12 pediatric cord blood transplants. These patients are undergoing outpatient treatment which will, over time, yield long-term survival information for this procedure. For adults, autologous transplants, allogeneic transplants from tissue-type matched relatives or from unrelated donors, and cord blood transplants are performed by the Emory University Hospital Bone Marrow and Stem Cell Transplant Center team.

Emory University Hospital is a 587-bed hospital located on the Emory University campus in northeast Atlanta. The Emory oncology program was recognized by U.S. News & World Report in its 1998 ranking of the "Best Hospitals in America." Emory University Hospital is a component of EMORY HEALTHCARE, which also includes Crawford Long Hospital, Emory's community-based hospital located in midtown Atlanta, The Emory Clinic and its 18 metro Atlanta health centers, Emory-Adventist Hospital in Smyrna (GA), The Emory Children¢s Center, and Wesley Woods Center in Atlanta.