Robert B. Geller, associate professor of medicine and director of Winship's expanded leukemia program, has begun a series of clinical trials in patients under the age of 65 with newly diagnosed and relapsed AML. More than 80 patients have been treated with a chemotherapy regimen more intensive in dose and duration than the standard, and a remission rate of more than 90 percent has been achieved for newly diagnosed patients. In relapsed patients, the remission rate with the more intensive therapy is 50 percent to 60 percent, compared to 30 percent to 40 percent with the conventional method.
In addition, Geller has had success with a new procedure called a peripheral blood stem cell (PBSC) transplant for patients who, with standard treatment, would have been candidates for chemotherapy alone or an autologous bone marrow transplant (a reinfusion of the patient's own bone marrow). Instead of harvesting bone marrow to obtain stem cells, cells are gathered from the patients' peripheral blood.
Studies show that peripheral blood has several advantages over bone marrow -- drawing blood is less invasive, requires no general anesthesia and may be less expensive than removing marrow; in most cases tumor contamination is less likely in peripheral blood; and in many patients bone marrow cells are unharvestable after chemotherapy.
After an initial course of chemotherapy, PBSC patients receive a growth factor to decrease toxicity of the chemotherapy and to quickly mobilize the healthy cells from the bone marrow to the peripheral blood. When there is no discernible evidence of leukemia in the blood, a sample is taken, cleansed for microscopic traces of disease, and frozen. The patient returns home for two to four weeks.
After returning for a second course of intensive chemotherapy, the patient is infused with the purged blood and waits as the marrow rebuilds itself. This process, called engraftment, takes just two weeks with PBSC. In conventional bone marrow transplantation, engraftment takes four to five weeks.
"The quicker the cells engraft the better, on every level," Geller explained. "The engraftment period is often fraught with unpleasant side effects --from the chemotherapy and from common infections the incubating immune system is too weak to stave off. Cutting recovery time in half means a lowered risk of life-threatening infections, a shorter, less expensive hospital stay and a big psychological boost for patients. They can look forward to resuming their lives that much sooner."
Vital to the success of a PBSC transplant is a new method developed at the Cancer Center for cleansing the extracted peripheral blood for reinfusion. Physicians can analyze cells and then separate, one at a time, the leukemia cells from the healthy stem cells. This is accomplished by adding a flourescent dye that attaches to two proteins found on the surface of the stem cells.
"Previously, we had only one known marker, leaving us with a cell population about 60 percent to 70 percent pure for stem cells," said Kent Holland, director of the hemopheresis unit, an integral part of the leukemia program. "Another more specific marker we have just developed gives us an ultra-purified population, about 99 percent pure stem cells."
Holland pointed out that formerly, the aim was to expunge the leukemia cells from the harvested bone marrow and reinfuse all the rest.
"With this new approach we select out the cells we want and actually enrich the patient's blood with the good cells," he explained. The improved purification method greatly reduces the number of cells needed for a transplant --from one or two liters to about a thimbleful. This aids in recovery because "the body does not have to use energy to clear out the cells it does not need."
Recent advances in cell sorting technology reveal its vast possibilities for the future. In the short term, scientists are confident that more protein markers will be identified to further purify the stem cell population. Eventually, the focus will be on the genetic manipulation of stem cells before they are reimplanted, to protect patients against certain disease. For instance, it is currently possible to sort uninfected stem cells from asymptomatic AIDS patients.
"If those stem cells could be manipulated to resist the virus when they are reimplanted, AIDS patients would be candidates for transplants. The same applies to blood and other immune disorders," said Holland. "This is a very exciting avenue of science."
-- Kate Egan