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Nonmyeloablative Stem Cell Transplant Promising for SLE


 

An autologous hematopoietic stem cell transplantation technique that achieves lymphoablation without myeloablation proved effective against severe refractory systemic lupus erythematosus in a preliminary study.

Serology, complement, immunomediated hemolysis and thrombocytopenia, thrombotic events, and pulmonary function all improved while preserving renal function in a single-center study of 48 patients. Nonmyeloablative hematopoietic stem cell transplantation (HSCT) significantly improved SLE symptoms and gave patients a 50% probability of 5-year remission, reported Dr. Richard K. Burt of Northwestern University, Chicago, and associates.

These results justify a randomized clinical trial comparing autologous HSCT with standard care, Dr. Burt and his associates said (JAMA 2006;295:527–35).

Fifty “very ill” patients underwent the two-step procedure involving a lupus-specific conditioning regimen to eliminate self-reactive lymphocytes followed by stem cell infusion. All had glomerulonephritis, lung involvement, CNS involvement, vasculitis, myositis, cytopenias, serositis, ulcerative mucocutaneous disease, and/or antiphospholipid syndrome refractory to optimal therapy.

One patient died from pulmonary and cerebral mucormycosis after stem cell mobilization but before transplantation (treatment-related mortality of 2%). A second patient died from active SLE after postponing transplantation.

The remaining 48 patients were followed for a mean of 29 months. Their probability of 5-year survival was 84%, and of disease-free 5-year survival 50%. Measures of serology, complement, and disease activity all remained improved throughout follow-up. Pulmonary function improved; five patients who had been dependent on supplemental oxygen were able to discontinue it.

Of 22 patients, 18 were able to discontinue anticoagulation without subsequent thrombotic events. Renal function remained stable or improved; 16 patients who had nephritis before HSCT were able to discontinue dialysis afterward. Idiopathic thrombocytopenic purpura cleared in five of seven patients. Autoimmune hemolytic anemia cleared in three of five patients.