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Life-threatening lupus responds to stem cell transplant therapy


Transplanting patients with blood stem cells that originate from their own bone marrow can induce the remission of life-threatening, treatment-resistant lupus, according to a study that took place at Northwestern Memorial Hospital in Chicago. Researchers found that 50 percent of the 50 patients in the study had disease-free survival at five years with an overall five-year survival rate of 84 percent. The study is published in the February 1 issue of the Journal of the American Medical Association.

Lupus, an autoimmune disease in which immune cells attack an individual’s own organs, affects an estimated 1.5 million people, mostly young females. "For this study, we enrolled patients who had either life- or organ-threatening lupus and had exhausted all available treatment options," says lead author Richard Burt, MD, chief, Division of Immunotherapy for Autoimmune Diseases, Northwestern Memorial Hospital in Chicago and associate professor of Medicine at Northwestern University’s Feinberg School of Medicine. "We found that within an experienced center, high-dose chemotherapy and autologous stem cell transplant may be performed safely and result in disease remission and improvement or salvage of residual organ function in the majority of patients."

The study, which was launched in 1997 when Dr. Burt performed the country’s first stem cell transplant to treat lupus, enrolled 50 patients from 20 states and ran through January 2005. The authors conclude that that the findings provide the justification to launch a randomized study that would compare autologous stem cell transplant with continued standard of care.

The stem cell transplant process used in the study is similar to that done to treat some forms of cancer. The patients’ own bone marrow stem cells were harvested from their blood. These cells, which can become different kinds of blood and immune system cells in the body, were then separated from the other blood cells. Next, in a process that usually requires a few weeks of hospitalization, patients immune systems were virtually destroyed through high doses of chemotherapy. Then the cleansed stem cells were returned to the bone marrow to repopulate the marrow and body in an effort to regenerate a healthier immune system. "The idea is that if you turn back the clock and let the immune system heal itself, the patient should have a chance of ending up without the disease," says Dr. Burt.

A European multi-center trial published in 2004 reported a similar success rate; however the treatment-related mortality rate was much higher at 13 percent, compared to a 2 percent rate in this study. The authors note that the toxicity of the treatment is a result of patient selection, the conditioning regimen and supportive care during and after transplantation. "It is doubtful our lower treatment mortality rate was due to patient selection, as our patients were very ill," says co-author Yu Oyama, MD, an autoimmune disease specialist at Northwestern Memorial Hospital and assistant professor, Division of Immunotherapy for Autoimmune Diseases at the Feinberg School of Medicine.

"A center effect on survival has also been reported for stem cell transplantation in malignancies," says Dr. Burt. "However, it’s important to note that the patients in this study are not comparable to those with malignancies. The patients in this study had organ dysfunction and were immunocompromised for a long time, conditions which often rule out stem cell transplant for cancer patients because it would be too dangerous. This highlights the importance for a medical center to have experience when treating lupus patients with high-dose chemotherapy and stem cell transplant."

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.

"Fortunately, the majority of patients with lupus can be successfully managed with our available medical therapies," says co-author Walter G. Barr, MD, a rheumatologist at Northwestern Memorial Hospital and professor of Medicine in the Division of Rheumatology at Northwestern University’s Feinberg School of Medicine. "However, for the very severely ill subset of lupus patients who have failed conventional therapies, stem cell transplantation provides a promising new alternative."

Amanda Widtfeldt | EurekAlert!
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