Parameters of improvement in patients with rheumatoid arthritis treated with cyclophosphamide

Abstract

Nine patients with rheumatoid arthritis were treated with cyclophosphamide. A significant decrease in joint score was seen in 8 patients after 2 months of treatment. At this time there were significant decreases in the monocyte and small lymphocyte counts. Leukopenia was not observed nor were significant changes in other common laboratory parameters observed at this time. Significant decreases in immunoglobulin levels occurred only after 10 months of treatment. Total depletion of small lymphocytes occurred in 7 of 9 patients at 33 weeks. These findings suggest that improvement on cyclophosphamide may be related to decreases in circulating small lymphocytes and monocytes and that levels of these cells in blood rather than the development of leukopenia be used as a guide to dosage. sequent trials have also shown a beneficial effect from the drug (3-5). The present investigation was undertaken to evaluate laboratory parameters which might be related to clinical improvement on cyclophosphamide. Particular attention was given to the effects of the drug on peripheral blood leukocytes, especially mononuclear cells. MATERIALS AND METHODSNine patients with classic rheumatoid arthritis were followed weekly over a I&month period in the Parkland Memorial Hospital outpatient arthritis clinic. Two were males and 7 were females; average age 49 years (range 29-62 yr). One had vasculitis, as evidenced by peripheral neuropathy, one Sjogren's Syndrome, and two episcleritis. Five patients were in functional class I1 and 4 in class 111. All patients were treated initially with cyclophosphamide in a dose of 2 mg/kg. The average daily dose of cyclophosphamide during the treatment period was 121 mg (range 75-200 mg) or 1-1.5 mg/ kg. This dose was continued unless leukopenia or other toxicity developed. In the presence of leukopenia the dose was reduced. The average dose of 72

Immunosuppressive and antiinflammatory properties of cyclophosphamide, azathioprine and methotrexate

“…In our laboratory (10) we have demonstrated that in NZB mice, cyclophosphamide primarily decreases the numbers of recirculating small lymphocytes in the blood, whereas 6 M P preferentially reduces the numbers of polymorphonuclear leukocytes and large mononuclear cells. In studies to be reported later (21) we have noted eventual total depletion of small lymphocytes in the majority of our patients on cyclophosphamide. Finally, Petrov and co- (23) have also shown that cyclophosphamide has a selective lymphotoxic action, while 6 M P and,azathioprine had only mitostatic properties and no effect on nondividing lymphoid cells.…”

Cyclophosphamide and lymphocyte subpopulations in Wegener's granulomatosis

“…The lymphocytes in culture are capable of a normal blastogenic response as shown by the normal response to mitogens. Monocytopenia is a feature of cyclophosphamide therapy (27) and was seen in our patients (28). However the lymphocyte to monocyte ratios in the present cultures were the same for all groups studied.…”

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

“…These include the presence of serologic abnormalities in RA patients, infiltration of the RA synovium with lymphocytes (1), the role of lymphocytes in animal models of RA (2)(3)(4)(5)(6)(7), and modulation of lymphocyte populations or function Jay Higgs' present by drugs or other measures that are used in the treatment of RA (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), such as cyclosporine A (20).…”