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June 2001

From University of Maryland Medical Center

Greenebaum Cancer Center studies ways to boost immunity for patients who undergo marrow and stem cell transplants

Using patientís own immune cells, physicians study potential of new therapy approach

The University of Maryland Greenebaum Cancer Center has begun two innovative stem cell transplant studies that look at ways to bolster a patientís immune system in an effort to protect the patient from infection and make the transplant itself more effective.

Both studies utilize a patientís own immune cells, which are collected prior to the transplant, activated and then re-infused post-transplant. One study also incorporates the injection of a new vaccine for chickenpox that may enhance the immune systemís ability to prevent shingles after a transplant.

The University of Maryland Greenebaum Cancer Center and the University of Pennsylania Cancer Center are the only two sites nationwide offering these studies to patients suffering from multiple myeloma or chronic myelogenous leukemia (CML). Both are cancers of the bone marrow that are thought to respond to therapies that stimulate the immune system.

"In the case of myeloma, treatment with high-dose chemotherapy followed by autologous stem cell transplant using the patientís own stem cells is considered to be the best therapy currently available," says Aaron Rapoport, M.D., associate professor of medicine at the University of Maryland School of Medicine and director of Lymphoma-Gene Medicine at the University of Maryland Greenebaum Cancer Center. "However, even high-dose therapy is rarely curative and most patients will eventually have recurrence of disease. Our hope with this study is to apply a strategy to boost the immune system after the transplant in order to treat the myeloma or CML and prolong the remission or response that follows."

Physicians are hoping to achieve a higher response rate by collecting and expanding the patientís own cancer and infection-fighting cells, known as "T-cells," prior to a stem cell transplant procedure.

The immune "T-cells" will be collected shortly after a patient has been diagnosed with myeloma or CML, when those cells will be more plentiful. The cells will then be treated in the lab by mixing them with antibodies (proteins) that bind to important targets (receptors) on the surface of the T-cells to stimulate and activate them. This procedure is an attempt to copy what should normally happen when the body encounters foreign cells like cancer cells. The cells are then infused back into the patient after chemotherapy.

"This treatment is thought to provide a critical second signal to the cells that is otherwise lacking in patients with certain types of cancers," explains Dr. Rapoport.

Another interesting objective of the myeloma study is to look at whether a new vaccine for chickenpox might also be beneficial for myeloma patients undergoing a bone marrow transplant. Shingles occurs in up to one-third of patients who have an autologous transplant for various hematologic malignancies. It causes a painful skin rash that sometimes spreads to other tissues and organs, such as the eyes, lungs, liver and nervous system.

"This new vaccine may boost the patientís immunity to the chickenpox virus and thereby prevent shingles, which can cause severe pain and, occassionally, life-threatening complications," says Dr. Rapoport. "We hope it may prevent or reduce the severity of shingles after a transplant and it may help us learn new ways to boost the immune system so that patients can respond more effectively to other vaccines for cancers or infectious organisms."

Patients who are eligible for the myeloma study include those recently diagnosed with multiple myeloma. Patients who are eligible for the CML trial include those who do not have a suitable bone marrow donor and have had unsatisfactory responses to front-line therapies, such as Gleevac or interferon alpha.

These studies represent an exciting era of research for physicians and scientists. Research in the field of blood and marrow-related cancers has often paved the way for advances in the treatment of other types of malignancies. The University of Maryland Greenebaum Cancer Center has become a major center for autologous transplants for multiple myeloma patients, particularly in the mid-Atlantic region.

The bone marrow transplant unit performs approximately 125 transplants per year in a modern, 16-bed inpatient facility that includes eight full-time oncologists. The center treats 10-15 new CML patients annually and about 30 multiple myeloma patients receive autologous transplants each year.

Marrow and stem cell transplants help cure many patients with blood-related cancers. Such patients may receive stem cell donations from siblings or unrelated donors, but only one-third of patients have a closely matched donor available. Thus, finding new ways to make an autologous transplant more effective is gaining increased attention.

"Allogeneic or "donor" transplants are not available to many patients with these diseases," says Dr. Rapoport. "What this study is attempting to do is harness the patientís own immune system to do what normally occurs in a donor transplant situation where the patient gets immune cells from the donor as well as stem cells. These immune cells can mount an important anti-tumor effect and help to cure the disease. We are trying to generate a similar effect in the autologous setting."

Preliminary results presented in December at the American Society of Hematologyís annual meeting showed that two CML patients studied so far had hematologic remissions for more than a year and one patient had a complete remission that has lasted for more than a year.

Dr. Rapoport has been selected to receive a Leukemia & Lymphoma Society Scholar in Clinical Research Award to help fund these research studies.

Patients who want more information may call 1-800-492-5538 or visit www.umm.edu.











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