Scleroderma, which means “hard skin,” is a rare disease that causes tissue to become hard and thick. Affected areas usually include the skin on the arms, legs, or trunk. Scleroderma can also cause swelling or pain in the joints and muscles. In severe, life-threatening forms, tissues of the lungs, heart, kidneys, or other internal organs can also be damaged. Researchers believe the disease may be caused by your immune system attacking your own body. To manage symptoms, doctors often prescribe cyclophosphamide, an immune-suppressing drug.
Researchers have been studying autologous hematopoietic stem cell transplants for treating scleroderma. In this approach, doctors first collect the participant’s blood-forming stem cells. Next, cells in the bone marrow are killed using either radiation therapy or chemotherapy, or a combination. The patients then receive a transplant of their own blood-forming stem cells. The stem cells move through the bloodstream to the bone marrow and make new blood cells. Radiation and chemotherapy can cause severe side effects, so doctors strive to minimize the doses used.
Previous studies of hematopoietic stem cell transplantation for scleroderma used regimens of chemotherapeutic drugs to reduce, but not completely destroy, the population of cells in the bone marrow. However, the results from those early studies didn’t change clinical practice in the United States, in part because of concerns about safety and the durability of treatment responses.
A research team led by Dr. Keith M. Sullivan at Duke University set out to assess a procedure called myeloablative transplantation, which uses chemotherapy and total body radiation to destroy the bone marrow before the autologous hematopoietic stem cell transplant. They compared this approach to treatment with monthly doses of cyclophosphamide in people with severe scleroderma involving the lungs or kidneys. The study was funded by NIH’s National Institute of Allergy and Infectious Diseases. Results appeared in the New England Journal of Medicine on January 4, 2018.
Researchers at 26 U.S. and Canadian sites randomly assigned 36 people with severe scleroderma to receive the hematopoietic stem cell procedure and 39 to receive one year of cyclophosphamide. After being monitored for 54 months, people who received the transplant procedure had significantly better health outcomes overall than those who received cyclophosphamide. Both types of treatment caused side effects, such as infections.
“We need effective therapies for scleroderma and other severe autoimmune diseases, which can be not only debilitating to the patient but also difficult to treat,” says NIAID Director Dr. Anthony S. Fauci. “These results add to the growing evidence that stem cell transplants should be considered as a potential treatment option for people with poor-prognosis scleroderma.”
“While treatment decisions should always be made on an individual basis, we hope that our work will help define a new standard of care for this severe, life-threatening autoimmune disease,” Sullivan says.
The investigators continue to follow study participants to assess long-term health outcomes.