Rheumatology Advance Access published online on February 22, 2007
Rheumatology, doi:10.1093/rheumatology/kem001
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Long-term effects of combination treatment with fludarabine and low-dose pulse cyclophosphamide in patients with lupus nephritis
1Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, 2National Institute of Diabetes and Digestive and Kidney Diseases, 3Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA and 4Division of Rheumatology, Clinical Immunology and Allergy, University of Crete Medical School, 711 10 Heraklion, Greece.
Correspondence to:
G. G. Illei, MD, Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Center Drive, Building 10 Room 9S205, Bethesda, MD 20892, USA. E-mail: illeig{at}mail.nih.gov
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Abstract |
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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.
KEY WORDS: systemic lupus erythematosus, chemotherapy, myelosuppression, remission, safety
Submitted 24 May 2006;
revised version accepted 3 January 2007.
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