Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial.

To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.

[1]  A. Spiers,et al.  Hemorrhagic cystitis after low-dose cyclophosphamide. , 1983, Lancet.

[2]  L. Wilkins.  Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo--final report. , 1970 .

[3]  P. Delmotte,et al.  Intensive immunosuppression with cyclophosphamide in multiple sclerosis , 1977, Journal of Neurology.

[4]  A. Steinberg.  Cyclophosphamide: should it be used daily, monthly, or never? , 1984, The New England journal of medicine.

[5]  A. Steinberg,et al.  Cyclophosphamide: use in practice. , 1974, Annals of internal medicine.

[6]  R. Eldridge.  The torsion dystonias , 1970, Neurology.

[7]  D. Drachman,et al.  Cyclophosphamide in exacerbations of multiple sclerosis. Therapeutic trial and a strategy for pilot drug studies. , 1975, Journal of neurology, neurosurgery, and psychiatry.

[8]  J. Kurtzke,et al.  On the evaluation of disability in multiple sclerosis , 1961, Neurology.

[9]  A. Hirata,et al.  Age dependent differential effects of cyclophosphamide on natural antibody levels in chickens. , 1982, Developmental and comparative immunology.

[10]  E. Korn,et al.  Difference in effect of single immunosuppressive agents (cyclophosphamide, CCNU, 5-FU) on peripheral blood immune cell parameters and central nervous system immunoglobulin synthesis rate in patients with multiple sclerosis. , 1983, Clinical and experimental immunology.

[11]  H. Miller,et al.  Cyclophosphamide in multiple sclerosis. , 1969, Lancet.

[12]  J. Kurtzke,et al.  Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs placebo in acute exacerbation. , 1969, Transactions of the American Neurological Association.

[13]  H. Weiner,et al.  Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. , 1983, The New England journal of medicine.

[14]  D. Silberberg.  Clinical Trials in Multiple Sclerosis: Problems and Opportunities , 1984 .

[15]  J. Atkinson,et al.  Bladder toxicity with chronic oral cyclophosphamide therapy in nonmalignant disease. , 1973, Arthritis and rheumatism.

[16]  J. Barry,et al.  Uroepithelial carcinoma in association with cyclophosphamide ingestion. , 1981, The Journal of urology.

[17]  W. Cendrowski.  Combined therapeutic trial in multiple sclerosis: hydrocortisone hemisuccinate with cyclophosphamide or cytosine arabinoside. , 1973, Acta neurologica Belgica.

[18]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[19]  O. Hommes,et al.  T-cell subpopulations in blood and cerebrospinal fluid of multiple sclerosis patients: effect of cyclophosphamide. , 1983, Clinical immunology and immunopathology.

[20]  M. R. Mickey,et al.  An illness severity score for multiple sclerosis , 1984, Neurology.

[21]  D. Grauman,et al.  Bladder complications in patients receiving cyclophosphamide for systemic lupus erythematosus or rheumatoid arthritis. , 1979, Annals of internal medicine.

[22]  A. Fauci,et al.  Activation of human B lymphocytes. XII. Differential effects of in vitro cyclophosphamide on human lymphocyte subpopulations involved in B-cell activation. , 1980, Immunology.

[23]  J. Kurtzke.  A New Scale for Evaluating Disability in Multiple Sclerosis , 1955, Neurology.

[24]  J. Vandenbroucke,et al.  The occurrence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide: a controlled retrospective follow-up. , 1983, Annals of the rheumatic diseases.

[25]  W. Johnson,et al.  Urinary-bladder fibrosis and telangiectasia associated with long-term cyclophosphamide therapy. , 1971, The New England journal of medicine.

[26]  R. Bast,et al.  Contrasting effects of cyclophosphamide and prednisolone on the phenotype of human peripheral blood leukocytes. , 1983, Clinical immunology and immunopathology.

[27]  R. Loewenson,et al.  The design of clinical studies to assess therapeutic efficacy in multiple sclerosis , 1979, Neurology.

[28]  F. L. Shand.  The immunopharmacology of cyclophosphamide. , 1979, International journal of immunopharmacology.

[29]  A. Fauci,et al.  Suppression of human B lymphocyte function by cyclophosphamide. , 1982, Journal of immunology.

[30]  S. Staugaitis,et al.  The basis of intra‐blood‐brain‐barrier IgG synthesis , 1985, Annals of neurology.

[31]  B. Haynes,et al.  Cyclophosphamide therapy of severe systemic necrotizing vasculitis. , 1979, The New England journal of medicine.

[32]  P. Schellekens,et al.  Evaluation of the immunosuppressive effects of cyclophosphamide in patients with multiple sclerosis. , 1982, Clinical and experimental immunology.

[33]  S. Fahn,et al.  Huntington disease , 1979, Neurology.

[34]  O. Hommes,et al.  Treatment of the chronic progressive form of multiple sclerosis with a combination of cyclophosphamide and prednisone , 1975, Clinical Neurology and Neurosurgery.

[35]  K. Syndulko,et al.  Quantitative Examination Of Neurologic Functions , 1985 .

[36]  G. Wheeler.  Cyclophosphamide-associated leukemia in Wegener's granulomatosis. , 1981, Annals of internal medicine.

[37]  J. Kurtzke,et al.  Further notes on disability evaluation in multiple sclerosis, with scale modifications , 1965, Neurology.