Background and Objectives: These studies explore the role of fludarabine as a therapeutic alternative for treatment-resistant autoimmune rheumatic diseases such as rheumatoid and soriatic arthritis, and systemic lupus erythematosus. The clinical efficacy, toxicity, and immunological effects of fludarabine are studied in patients with autoimmune rheumatic disorders in phase I/II clinical studies. Fludarabine primarily affects lymphoid cells because these cells have small amounts of the enzyme necessary to metabolize fludarabine. Previous investigations employing this drug in patients with low-grade lymphoid malignancies have shown that it selectively targets immune cells by inducing a physiologic form of cell death called apoptosis. However, it's effects on the clinical course of immunologic diseases, as well as on the function and regeneration of immune cells have not been characterized. Results 1) Rheumatoid Arthritis (RA) In a two dose (20 and 30 mg/m2) open label clinical trial 26 patients with severe RA refractory to treatment were treated with fludarabine for 6 months. Using intention to treat analysis, 17% of patients in the low dose group and 36 % in the high dose group met ACR criteria for 20% improvement. Significant lymphopenia involving both naive and memory T cells (naive
