Long-term effects of combination treatment with fludarabine and low-dose pulse cyclophosphamide in patients with lupus nephritis

• Published in: Rheumatology (Oxford, England) Vol. 46; no. 6; pp. 952 - 956
• Main Authors: Illei, G. G., Yarboro, C. H., Kuroiwa, T., Schlimgen, R., Austin, H. A., Tisdale, J. F., Chitkara, P., Fleisher, T., Klippel, J. H., Balow, J. E., Boumpas, D. T.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-06-2007; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Biological and medical sciences; CD4 Lymphocyte Count; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Kidneys; Lupus Nephritis - drug therapy; Lymphopenia - chemically induced; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Neutropenia - chemically induced; Pilot Projects; Proteinuria - drug therapy; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Treatment Outcome; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Vidarabine - adverse effects; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; systemic lupus erythematosus; chemotherapy; myelosuppression; safety; remission; Antineoplastic agent; Skin disease; Toxicity; Autoimmune disease; Hemopathy; Lupus nephritis; Systemic lupus erythematosus; Systemic disease; Bone marrow; Remission; Lymphocytopenia; Kidney disease; Human; Corticosteroid; Immunopathology; Purine nucleotide; Connective tissue disease; Nervous system diseases; Herpes zoster; Urinary system disease; Leukopenia; Low dose; Antiinflammatory agent; Graft versus host reaction; Prednisone; Long term; Infection; Alkylating agent; Oxazaphosphinane derivatives; Chemotherapy; Cyclophosphamide; Fludarabine; Treatment; Antimetabolic; Nitrogen mustard; Viral disease; Adrenal hormone; Fluorine Organic compounds; Immunosuppressive agent; Proteinuria
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kem001

Objectives. To determine the safety and efficacy of a short course of fludarabine combined with cyclophoshamide in lupus nephritis.
Methods. A phase I/II open label pilot study. Thirteen patients with active proliferative lupus nephritis received monthly oral boluses of low-dose cyclophoshamide (0.5 gm/m2 on day 1) and subcutaneous fludarabine (30 mg/m2 on days 1-3) for 3-6 cycles. Concomitant prednisone was aggressively tapered from 0.5 mg/kg/day to a low-dose, alternate-day schedule. Patients were followed for at least 24 months after therapy. The primary outcome was the number of patients achieving renal remission defined as stable creatinine, proteinuria <1 gm/day and inactive urine sediment for at least 6 months.
Results. The study was terminated early because of bone marrow toxicity. Eleven patients who received at least three cycles were evaluated for efficacy. Ten patients improved markedly with seven patients achieving complete remission and three patients achieving partial remission. There were three serious haematological adverse events during the treatment with one death due to transfusion-associated graft vs host disease. Profound and prolonged CD4 (mean CD4: 98/µl at 7 months and 251/µl at 12 months) and CD20 lymphocytopenia was noted in most patients. Three patients developed Herpes zoster infections.
Conclusions. A short course of low-dose fludarabine and cyclophoshamide can induce long-lasting remissions in patients with proliferative lupus nephritis, but severe myelosuppression limits its widespread use.