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December 14, 1998

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Hopkins Researchers Develop New Therapy for Autoimmune Disorders such as Rheumatoid Arthritis and Lupus

Researchers at the Johns Hopkins Oncology Center used high doses of the chemotherapy drug cyclophosphamide alone to control previously untreatable forms of autoimmune disorders such as rheumatoid arthritis, lupus and hemolytic anemia.

Their findings are reported in the December 15, 1998 issue of Annals of Internal Medicine. Of eight patients treated in the study with stand-alone high dose cyclophosphamide, five reported complete remissions and two achieved and maintained partial remissions. Four patients treated from six months to more than a year ago remain disease free, and two patients, in partial remission, continue to improve after more than a year. In addition, all patients were able to decrease their doses of medication, and three patients have completely discontinued medications for their disease. These patients had not responded to disease therapies and suffered from recurrent infections, persistent pain and kidney problems.

Treatment for severe autoimmune diseases using high-dose cyclophosphamide followed by bone marrow or stem cell transplantation to repopulate the immune system destroyed by the drug treatment is being studied elsewhere. The new Hopkins research, funded by the National Institutes of Health, suggests that transplants are unnecessary. "Stem cells, the marrow cells that reconstitute the immune system, are resistant to the drug and will repopulate in the marrow, without the need for transplantation," says Robert Brodsky, M.D., assistant professor of oncology and medicine and lead author of the study. "High-dose cyclophosphamide, without stem cell or bone marrow reinfusion, appears to be safer for the patient and avoids reinfusion of diseased immune cells," adds Brodsky, an American Society of Hematology Junior Faculty Scholar.

Hopkins scientists believe the cyclophosphamide works by reprogramming the immune system. "Immunity is learned' not inherited," explains Richard Jones, M.D., associate professor of oncology and director of Bone Marrow Transplantation at the Johns Hopkins Oncology Center. "We acquire immunity through vaccinations and exposure to organisms which teach immune cells to recognize and attack foreign bodies." In people with autoimmune disorders, the immune system attacks its own tissues and organs and must be re-taught to differentiate between the body's own cells and foreign attackers. "This therapy is analogous to rebooting a computer--you wipe out the old information, then allow it to re-learn. The immune system that returns should function normally," says Jones.

While the researchers are optimistic about these results, they caution that additional research and a larger number of patients are necessary to confirm these findings. They are now expanding the study to include additional patients with severe autoimmune disorders.

In addition to Jones and Brodsky, other research participants included Michelle Petri, M.D., M.P.H., B. Douglas Smith, M.D., Eric J. Seifter, M.D., Jerry L. Spivak, M.D., and Chi V. Dang, M.D., Ph.D., of Hopkins, and Michael Styler, M.D. and Isadore Brodsky, M.D., of Hahnemann University.


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