Researchers at Johns Hopkins, Hahnemann University and University of Maryland report sustained, treatment-free remissions in studies of a novel drug therapy approach to treating a deadly blood disorder known as aplastic anemia.

The Oct. 2 report in the Annals of Internal Medicine describes 19 aplastic anemia patients treated with high doses of the chemotherapy drug cyclophosphamide. After an average follow-up of more than two years, 14 patients remain disease-free with no additional therapy. Two patients continue to require transfusions, and three patients died from infections following treatment.

"Patients treated with high-dose cyclophosphamide alone typically take a longer time to recover normal blood counts than patients treated with other standard treatments; nevertheless, cyclophosphamide may offer a better chance for achieving long-term remission," says Robert Brodsky, assistant professor of oncology and medicine at Hopkins and lead author of the study. Two years after receiving the cyclophosphamide therapy, 73 percent of patients no longer required blood transfusions. Nearly four years post-treatment, 65 percent of those treated were in complete remission and had not relapsed or developed other blood disorders.

In aplastic anemia, the patient's immune system attacks the bone marrow, causing it to stop forming blood cells--white immune system cells, red oxygen-carrying cells and clotting cells known as platelets. Without these vital cells, patients are susceptible to life-threatening infections, bleeding and organ failure. Aplastic anemia is a rapidly fatal disease. Without treatment, 80 percent of patients die within two years.

The researchers report that treatment with high doses of cyclophosphamide eliminates the abnormal immune system. "It's much like rebooting a computer," Brodsky says. "The cyclophosphamide wipes out the old information and allows the immune system to relearn and begin functioning normally without any further therapy," he says.

Currently, standard treatment for patients with aplastic anemia is with immunosuppressive drugs or high-dose cyclophosphamide followed by a bone marrow transplant of healthy donor marrow. Immunosuppressive therapy, though initially effective, is linked to a high rate of relapse and other marrow disorders such as leukemia. Bone marrow transplant, while restoring blood counts more rapidly, is limited by the availability of appropriate bone marrow donors and such serious complications as infections and graft rejection.

This new study, as well as earlier studies by the Hopkins team, shows that most patients recover normal blood counts when treated with high-dose cyclophosphamide alone, without a marrow transplant. As a result, Brodsky believes these latest findings suggest the therapy may be a viable option for patients unable to receive a bone marrow transplant.

This research was funded by the National Institutes of Health. Brodsky is a Leukemia and Lymphoma Society Clinical Research Scholar. In addition to Brodsky, other research participants included Lyle L. Sensenbrenner, B. Douglas Smith, Donna Dorr, Philip J. Seaman, Shing M. Lee and Richard J. Jones, all from Hopkins; Judith E. Karp, from the University of Maryland Greenebaum Cancer Center; and Isadore Brodsky, from Hahnemann University.

Related Web Site
Johns Hopkins Oncology Center information on aplastic anemia