Stem Cell Transplants Tested as Therapy for Scleroderma

In a bold attempt to control a disabling and often fatal immune disease called scleroderma, physicians at Duke University Medical Center are leading a national study to test whether stem cell transplants can reconstruct defective immune systems.

If successful, the therapy would represent the first therapy ever to treat and potentially reverse the disease itself, not just alleviate its symptoms, said the Duke researchers.

"Current therapies treat the disease symptoms but they don't alter the course of the disease," said Keith Sullivan, M.D., a Duke oncologist in the division of cellular therapy and the study's lead investigator.

"We are hoping that transplantation will actually lessen or eradicate the defective immune response that initiates and perpetuates the disease."

The Duke-led study will increase the dose and duration of cyclophosphamide and compare this regimen against stem cell transplants, using purified stem cells derived from a patient's own blood.

"Our hope is to apply the benefits of stem cell transplantation to a chronic disease that can be severely disabling to some patients and fatal for others," said Sullivan.

"If the therapy is successful, we could potentially extend its application to other severe autoimmune diseases."

Transplants using stem cells from bone marrow or blood are considered a viable treatment for scleroderma because they replace the blood-forming and immune systems that give rise to these self -destructive abnormalities.

The SCOT study will compare the effects of stem cell transplantation versus twelve monthly doses of high-dose cyclophosphamide.

The seven-year, randomized clinical trial will evaluate differences in the death rates and significant organ damage between the two treatment groups.

Researchers at 36 collaborating university sites will conduct the trial while analyzing the molecular basis of the disease and how treatments impact immune and cellular function, gene expression, and vascular abnormalities.

"One of the primary questions we want to answer is whether we can chronically suppress the immune system for one year and subdue the disease, or whether we need to completely repopulate the immune system with purified stem cells," said Joseph Shanahan, MD, a Duke rheumatologist and co-investigator of the study.

Patients undergoing transplants will receive their own, purified blood stem cells through a process called an "autologous" transplant. Patients are first given drugs that stimulate the release of stem cells into their bloodstream.

The stem cells are then extracted from the blood, separated to remove lymphocytes, and stored for future use.

Only the primordial stem cells - those which have not yet begun to commit to be a specific cell type - will be extracted.

The patient's immune system is then destroyed using high doses of chemotherapy and radiation: the goal is to eradicate the immune cells responsible for attacking the body.

Following the immune destruction, the stored blood stem cells are re-infused into the patient and begin to repopulate the blood-forming and immune system.

Using the patient's own stem cells reduces the potential for complications that often arise when non-self donor blood or marrow are used.

Immune cell function will be measured pre- and post-transplant to determine the effects of the transplant upon the patient's immune system.