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Nonmyeloablative Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus
JAMA. 2006;295:527-535; Vol. 295 No. 5, 1Feb 2006    

Context  Manifestations of systemic lupus erythematosus (SLE) may in most patients be ameliorated with medications that suppress the immune system. Nevertheless, there remains a subset of SLE patients for whom current strategies are insufficient to control disease.

Objective  To assess the safety of intense immunosuppression and autologous hematopoietic stem cell support in patients with severe and treatment-refractory SLE.


Design, Setting, and Participants  A single-arm trial of 50 patients with SLE refractory to standard immunosuppressive therapies and either organ- or life-threatening visceral involvement. Patients were enrolled from April 1997 through January 2005 in an autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) study at a single US medical center.

Interventions  Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (5 µg/kg per day), enriched ex vivo by CD34+ immunoselection, cryopreserved, and reinfused after treatment with cyclophosphamide (200 mg/kg) and equine antithymocyte globulin (90 mg/kg).

Main Outcome Measures  The primary end point was survival, both overall and disease-free. Secondary end points included SLE Disease Activity Index (SLEDAI), serology (antinuclear antibody [ANA] and anti–double-stranded (ds) DNA), complement C3 and C4, and changes in renal and pulmonary organ function assessed before treatment and at 6 months, 12 months, and then yearly for 5 years.

Results  Fifty patients were enrolled and underwent stem cell mobilization. Two patients died after mobilization, one from disseminated mucormycosis and another from active lupus after postponing the transplantation for 4 months. Forty-eight patients underwent nonmyeloablative HSCT. Treatment-related mortality was 2% (1/50). By intention to treat, treatment-related mortality was 4% (2/50). With a mean follow-up of 29 months (range, 6 months to 7.5 years) for patients undergoing HSCT, overall 5-year survival was 84%, and probability of disease-free survival at 5 years following HSCT was 50%. Secondary analysis demonstrated stabilization of renal function and significant improvement in SLEDAI score, ANA, anti-ds DNA, complement, and carbon monoxide diffusion lung capacity adjusted for hemoglobin.

Conclusions  In treatment-refractory SLE, autologous nonmyeloablative HSCT results in amelioration of disease activity, improvement in serologic markers, and either stabilization or reversal of organ dysfunction. These data are nonrandomized and thus preliminary, providing the foundation and justification for a definitive randomized trial.

Clinical Trial Registration Identifier: NCT00271934
Richard K. Burt, MD; Ann Traynor, MD; Laisvyde Statkute, MD; Walter G. Barr, MD; Robert Rosa, MD; James Schroeder, MD; Larissa Verda, MD, PhD; Nela Krosnjar, MD; Kathleen Quigley, RN; Kimberly Yaung, RN; Marcello Villa, BS; Miyuki Takahashi, MD; Borko Jovanovic, PhD; Yu Oyama, MD
Author Affiliations: Division of Immunotherapy (Drs Burt, Traynor, Statkute, Verda, Krosnjar, Takahashi, and Oyama, Mss Quigley and Yaung, and Mr Villa), Division of Rheumatology (Drs Barr and Schroeder), Division of Nephrology (Dr Rosa), and Department of Preventive Medicine (Dr Jonanovic), Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Dr Traynor is now with the Division of Hematology/Oncology, University of Massachusetts, Worcester.

Journal of the American Medical Association report:

[Excerpts from related article]:

Thirty-three of the 48 patients with lupus who received the groundbreaking treatment from Chicago’s Northwestern Memorial Hospital have been symptom free ever since.

Ross and the others in the experimental group were among approximately 5% of lupus sufferers who have a form of the disease that responds poorly to standard therapy.

Ross said that since the treatment she feels “110 percent better,” and that she looks forward to completing a master’s degree. “It gave me my life back,” she said.

The autoimmune process attacks vital organs such as the heart, brain, and kidneys, and can be fatal. The most common treatment, prednisone, also causes numerous side effects such as thinning bones and weight gain – high doses in Ross’s case also left her with diabetes.

Lead researcher in the study, Dr. Richard Burt, said he was pleased with the outcome. “It turned out very well, showing that we could do this safely,” he said. Lupus afflicts about 1.5 million Americans, 90% of them women.

[, 2Feb06, Chicago;Vanderheyden]

Related: High-Dose Cyclophosphamide and Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus, Michelle Petri and Robert Brodsky
JAMA. 2006;295:559-560.