Study of hematopoietic stem cell transplantation for severe, treatment-resistant lupus

Researchers at the Department of Health and Human Services' National Institutes of Health (NIH) have launched a five-year study to see whether a therapy using transplantation of hematopoietic stem cells, blood stem cells found in bone marrow, can produce long-term remission for patients with severe, treatment-resistant systemic lupus erythematosus (or lupus), a rheumatic autoimmune disease that can affect the body's major organs. The study will include a basic research component to examine the roles of B and T cells, white blood cells in the immune system, in triggering lupus symptoms.

In this pilot study, 14 patients from ages 15 to 40 will receive stem cell transplantation therapy, during which their stem cells will be removed from their bone marrow. These cells, which will become different kinds of blood and immune system cells in the body, will then be harvested and cleaned. After the patient's bone marrow is treated with immunosuppressant drugs to destroy the disease-causing immune cells, the stem cells will be returned to the bone marrow. The stem cells will then repopulate the marrow and body to establish a more properly functioning immune system.

The initial treatment requires several outpatient visits followed by a two-week hospital stay. Patients then have monthly medical visits for six months, quarterly visits for two years, and annual visits for the remainder of the study. Following therapy, researchers will assess whether this treatment produces sustained, relapse-free disease remission for 24 months.

"Many patients with severe forms of lupus have limited treatment options that may offer only temporary relief of symptoms and no disease regression. For these patients, stem cell transplantation therapy may offer hope for a normal functioning immune system," said Stephen I. Katz, M.D., Ph.D., director of NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Severe forms of lupus can devastate patients, causing pain, fatigue, depression, and in some cases, premature death. Patients who enter this study must have been treated, to no avail, with high doses of immunosuppressant drugs, which decrease immune function. Researchers believe that by combining immunosuppressant treatment with stem cell transplantation, they can create a new immune system that doesn't attack the body's healthy cells.

"Advances in cancer therapy can yield advances in treatment of autoimmune diseases," said Andrew von Eschenbach, M.D., director of the NIH's National Cancer Institute. "Cyclophosphamide used as a cancer therapy suppresses the immune system. This discovery led to improvements for lupus patients. Similarly, altering the immune system through progenitor cell transplantation, a cancer treatment, may also benefit lupus patients."

"Lupus is different from cancer," he added. "However, we have found that both diseases can benefit from treatment that modulates the immune system."

In addition to the clinical study, researchers will look at how B and T cells function in the immune systems of lupus patients. Previous studies have shown that the dysfunctioning T cells, which normally regulate the immune response, coupled with overactive B cells, which target both foreign and healthy cells, are responsible for the destructive autoimmune process that takes place in lupus. Researchers will compare the activity of B and T cells extracted from patients before stem cell transplant therapy with those that repopulate in the "new" immune system after therapy. They will be looking for cell properties that may contribute to the faulty immune response found in lupus. B cell studies will be conducted by scientists at NIAMS, while T cell studies will be conducted by scientists at NCI.

Researchers at the National Institute of Neurological Disorders and Stroke and the National Institute of Diabetes and Digestive and Kidney Diseases will join this collaborative effort, investigating the central nervous system and kidney involvement, respectively, of lupus patients. "This study is an example of what can be accomplished when scientists from various disciplines combine resources and experience to create better outcomes for patients," said Dr. Katz.

Lupus is a chronic, inflammatory, autoimmune disease that mainly affects women of child-bearing age. Its symptoms range from unexplained fever, swollen joints and skin rashes to severe damage of the kidneys, lungs or central nervous system. Lupus is three times more common — and is frequently more severe — in African Americans and Hispanics/Latinos. Studies show these groups also experience more complications of lupus, including kidney failure for both and neurological problems for African Americans.

For additional information on this clinical study, please contact:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: (301) 594-9774 (local), 1-866-411-1010 (toll free)
or e-mail at [email protected]