Posted on 09/02/2006 9:37:18 PM PDT by Coleus
EVANSTON, Ill. -- A recent Northwestern University study found that a new treatment using stem cells might extend the lives of patients with lupus. Stem cell treatments could help patients with severe cases who have not responded to other options, according to a study published in the Feb. 1 issue of The Journal of the American Medical Association.
Lupus is a disease that causes patients' immune systems to become unable to distinguish between foreign substances and normal parts of the body. This causes the immune system to attack the patient's own cells and tissues instead of protecting them.
Researchers, including Richard Burt of NU's Feinberg School of Medicine, altered patient stem cells to replace the supply of some forms of white blood cells. These cells are involved in the immune system and often are defective in patients with lupus. After the stem cells were extracted, patients' existing white blood cells were destroyed using strong drug treatments similar to chemotherapy. The altered stem cells were then replaced in patients' bodies to produce new white blood cells.
Of the 48 patients who received stem cell transplants, about 50 percent were disease-free five years later. A potential risk associated with this treatment is that while the patients' existing white blood cells are being destroyed, patients are more susceptible to an infection. The study called for further research comparing survival rates of stem cell transplant patients with those who undergo traditional treatment.
JAMA. 2006;295:527-535.
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 antidouble-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 ClinicalTrials.gov Identifier: NCT00271934
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.
This Week in JAMA JAMA. 2006;295:469.
High-Dose Cyclophosphamide and Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus
Michelle Petri and Robert Brodsky JAMA. 2006;295:559-560.
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The problem here is the 5 year time span. Lupus and the other auto-immune problems come on very slowly. My bet is that the infection is hiding in other places and will get back into the immune system, it will just take longer than 5 years to show clinical symptoms.
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