Objective: High-dose chemotherapy followed by hematopoietic stem cell transplantation is increasingly being studied as a treatment for severe autoimmune disorders, such as systemic lupus erythematosus (SLE). High-dose cyclophosphamide, the foundation of virtually all conditioning regimens for stem cell transplantation, is not myeloablative; therefore, when high-dose cyclophosphamide is used alone, autografting, with its potential for reinfusing autoreactive effector cells, is not required. We undertook this study to investigate the safety and efficacy of high-dose cyclophosphamide without stem cell transplantation in refractory SLE.
Methods: We treated 14 patients with moderate-to-severe SLE that had been refractory to corticosteroids and one or more additional immunosuppressive drugs. All patients received 50 mg/kg of cyclophosphamide for 4 consecutive days followed by 5 microg/kg granulocyte colony-stimulating factor until the neutrophil count was 1 x 10(9)/liter for 2 consecutive days. Patients were followed up monthly for disease activity using the physician's global assessment, SLE Disease Activity Index, and assessment of functioning of involved organs. The Responder Index for Lupus Erythematosus was used to define partial or complete response.
Results: The median time to achieve a neutrophil count of 0.5 x 10(9)/liter was 14 days (range 11-22 days) after the last dose of cyclophosphamide. Patients required a median of 2 units (range 2-5) of packed red blood cells, and a median of 16 days (range 0-23 days) elapsed from the last dose of cyclophosphamide to the last platelet transfusion. There were no deaths or fungal infections. Significant improvements in physician's global assessment (mean difference 1.4; P < 0.0001), SLE Disease Activity Index (mean difference 4.1; P = 0.0039), and prednisone dosage (mean difference 14.9 mg/day; P = 0.002) were observed. Responses, including 5 durable complete responses, were observed in all organ systems (renal, central nervous system, and skin) with involvement that had led to patient enrollment.
Conclusion: High-dose cyclophosphamide without stem cell transplantation leads to rapid hematopoietic reconstitution and has significant clinical benefit in patients with refractory SLE. Therefore, this approach deserves further study.