Non-Myeloablative Autologous Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus.

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. Here we report results of autologous non-myeloablative hematopoietic stem cell transplantation single arm trial performed at Northwestern University Feinberg School of Medicine between February 1997 and January 2005 involving 50 patients with SLE refractory to standard immune suppressive therapies and either organ- or life-threatening visceral involvement. Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m²) and G-CSF (5 ug/kg/day), enriched ex vivo by CD34⁺ immunoselection, cryopreserved, and reinfused after treatment with cyclophosphamide (200 mg/kg) and equine anti-thymocyte globulin (90 mg/kg). The primary endpoint was survival, both overall survival and disease free survival. Secondary endpoints include systemic lupus erythematosus disease activity index (SLEDAI), serology (ANA and antids DNA), complement (C3 and C4), and changes in renal and pulmonary organ function assessed pre-treatment and 6 months, 12 months and then yearly for 5 years. 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 transplant for 4 months. Forty-eight patients underwent lupus non-myeloablative hematopoietic stem cell transplantation with no treatment related mortality. By intention to treat, treatment related mortality was 2% (1/50). With a mean follow-up of 29 months (range 6 month to 7.5 years ), overall survival was 84%, and probability of disease free survival at 5 years post transplant was 50%. Secondary analysis demonstrated stabilization of renal function and statistically significant improvement (p ≤ .05) in SLEDAI, ANA, anti-ds DNA, complement, and DLCO adjusted for hemoglobin (DLCOadj). In treatment refractory SLE, autologous non-myeloablative hematopoietic stem cell transplantation results in marked amelioration of disease activity, long term disease remission, improvement in serologic markers, and either stabilization or reversal of organ dysfunction.