Selective depletion of Ig‐bearing lymphocytes by cyclophosphamide in rheumatoid arthritis and systemic lupus erythematosu guidelines for dosage

Cyclophosphamide was given to 11 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in doses regulated by monitoring effects on small lymphocytes. Total leukocyte counts, the numbers of immunoglobulin‐positive and Ig‐negative small lymphocytes by immunofluorescence and the proliferative response of lymphocytes to phytohemagglutinin (PHA) were measured. The number of both Ig‐positive and Ig‐negative small lymphocytes decreased following cyclophosphamide. When dosage was reduced to maintenance levels, the Ig‐positive cells remained less than 75% of baseline values, whereas the Ig‐negative lymphocytes returned toward the baseline. During this time PHA values were normal or increased. On maintenance therapy, objective evidence of improvement was observed in 10 patients. These studies suggested a selective depletion of B‐lymphocytes by cyclophosphamide and that a reduction of other leukocytes is not necessary for a favorable clinical response. Adverse side effects were rare. Direct quantitation of B‐lymphocytes may be helpful in regulating clinically effective individual doses of cyclophosphamide in a manner that is relatively safe.