High-Dose Cyclophosphamide Promising in Refractory Lupus

Laurie Barclay, MD

Jan. 8, 2003 — Refractory systemic lupus erythematosus (SLE) may respond to high-dose cyclophosphamide without stem cell transplantation, according to the results of a small study in the January issue of Arthritis & Rheumatism. A randomized trial is underway.

“There is now great optimism that high-dose cyclophosphamide therapy followed by hematopoietic stem cell transplantation might induce treatment-free remission in a variety of severe autoimmune diseases,” write Michelle Petri, MD, and colleagues from Johns Hopkins University in Baltimore, Maryland. “When high-dose cyclophosphamide is used alone, autografting, with its potential for reinfusing autoreactive effector cells, is not required.”

Of 14 patients with moderate to severe SLE refractory to steroids plus one or more immunosuppressive drugs, 12 were female, four were African-American, nine had progressive renal lupus, and one had an ulcerating lupus rash covering 60% of her body. Mean age was 35 years.

Treatment consisted of 50 mg/kg cyclophosphamide for four consecutive days followed by 5 µg/kg granulocyte colony-stimulating factor (G-CSF) until the neutrophil count was 1 x 109/L for two consecutive days. Median duration of G-CSF therapy was 14 days (range, 11-22 days). Patients also received supportive care, including packed red blood cell and platelet transfusions.

There were no fungal infections, deaths, mucositis greater than grade 1, or premature ovarian failure. Five patients achieved a durable complete response, as defined by the Responder Index for Lupus Erythematosus, in all involved organ systems including kidney, central nervous system, and skin. Six additional patients had a partial response. Physician’s global assessment, SLE Disease Activity Index, and prednisone dosage all improved significantly (P < .0001, P = .0039, and P = .002, respectively).

High-dose cyclophosphamide was well tolerated, with the most common adverse events being nausea, alopecia, transient aplasia, and febrile neutropenia. However, some patients suffered relapses.

“High-dose cyclophosphamide without stem cell transplantation warrants further study in severe autoimmune diseases, including SLE,” the authors write. “A randomized trial comparing high-dose cyclophosphamide with the National Institutes of Health monthly IV cyclophosphamide regimen in SLE is already underway.”

Arthritis Rheum. 2003;48(1):166-173

Reviewed by Gary D. Vogin, MD

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