NEW ORLEANS — Patients with refractory systemic lupus erythematosus have had “substantial improvements” following autologous stem cell transplants in an uncontrolled, phase I-II study.
The next step is to test the treatment in a randomized, controlled trial, Richard Burt, M.D., said at the southern regional meeting of the American Federation for Medical Research.
As of February, Dr. Burt had followed 48 patients treated with nonmyeloablative stem cell transplants and found that they stayed in remission for as long as 88 months and for an average of 33 months.
Among patients followed for at least 2 years, 70% were in remission; after at least 5 years, 50% were in remission, said Dr. Burt, chief of the division of immunotherapy and autoimmune diseases at Northwestern University in Chicago. He defined remission as requiring less than 10 mg/day of prednisone. Before receiving stem cell transplants, these patients required 50-100 mg of prednisone daily.
The treatment aims to ablate a patient's dysfunctional immune system and then regenerate immunity with autologous stem cells. In patients with systemic lupus erythematosus (SLE), as well as other autoimmune diseases, the pathologic defect is presumed to be environmental and not genetic, and hence the patient's stem cells should be able to regenerate a more normally functioning immune system.
A key to the success of this program is that patients receive a conditioning regimen that is immunoablative but not myeloablative. This makes the treatment safer, Dr. Burt said.
The series enrolled patients who had steroid-dependent SLE, with an average age of 26 years; 87% were women.
Stem cells were mobilized by using a combination of low-dose cyclophosphamide and granulocyte colony-stimulating factor. Stem cells were harvested 10 days later. Patients were then immunoablated with a combination regimen of high-dose cyclophosphamide, a total of 200 mg/kg, along with equine antithymocyte globulin to eliminate T cells. After the ablative regimen was complete, patients received an infusion of their autologous stem cells.
During recovery, patients required an average of six red blood cell transfusions and seven platelet transfusions. Adequate neurophil recovery usually occurred within 9 days after completion of the immunoablative treatment, and platelets usually recovered by day 12.
Patients generally were discharged from the hospital 14 days after immunoablation.
Following treatment, patients had a marked reduction in their level of antinuclear antibody and an increase in complement, so that levels returned to the normal range. Proteinuria severity also improved markedly, with reductions of about 75%. Many patients have also had resolution of pneumonitis or alveolar hemorrhage.
Antiphospholipid antibody levels dropped, enabling about 80% of patients to stop chronic treatment with anticoagulants without the occurrence of thrombotic events during a mean of 17 months.
Since the start of this study 7 years ago, four patients have died from disease relapse, one has died following a traumatic accident, and one has died from an unrelated, late infection.
Dr. Burt believes this treatment is probably applicable to several different autoimmune diseases. He and his associates have already used it safely and with encouraging results in patients with other autoimmune disorders, including Crohn's disease and multiple sclerosis.