Cyclophosphamide: to pulse or not to pulse?

Article Abstract:

Cyclophosphamide (CP) is an anticancer drug that also has immunosuppressive effects, which make it useful for treating autoimmune diseases, such as systemic lupus erythematosus (SLE). However, CP can be toxic even at therapeutic doses. To try to decrease the long-term toxic effects, such as cancer, bladder dysfunction, and bone marrow suppression, intermittent high-dose CP (pulse CP) has served as a successful alternative to daily low-dose therapy in the treatment of SLE. The resulting effectiveness and reduced toxicity have led many to assume that the same CP dosage regimen would also be effective in treating other diseases responsive to this agent. However, a report by Hoffman et al. in the October 1990 issue of The American Journal of Medicine raises questions about pulse CP treatment of Wegener's granulomatosis (WG). WG is characterized by vasculitis (inflammation of blood vessels), granulomatous lesions (tumors containing granular white blood cells), and kidney dysfunction. The disease is fatal if not treated early. In this study, only 21 percent of the WG patients experienced remission with pulse CP; this is much lower than the success rate achieved with daily low-dose CP. Similarly, the manifestations of SLE that are responsive to pulse CP are not generally mediated by vasculitis. Although long-term toxicity is generally avoided with pulse CP, granulocytopenia is a prominent short-term effect that may still occur. (It is related to bone marrow suppression and characterized by low levels of granular white blood cells.) Questions concerning the therapeutic use and dosage regimen of CP remain to be answered. Particularly important are: identifying groups of patients with vasculitis disorders who may benefit from pulsed CP; exploring alternative treatments, such as combinations of immunosuppressive agents; modifying pulse CP protocols; and using less toxic maintenance regiments after disease remission. Well-designed trials, similar to the one reported by Hoffman and coworkers, are needed to address these issues. (Consumer Summary produced by Reliance Medical Information, Inc.)

Systemic lupus erythematosus, Vasculitis, editorial

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Frequent occurrence of asplenism and cholelithiasis in patients with autoimmune polyglandular disease type I

Article Abstract:

Autoimmune polyglandular disease type I (APG I) is a condition in which the functioning of the parathyroid and adrenal glands is impaired and candidiasis (a fungal infection) develops in mucous membranes. Other symptoms include insulin-dependent diabetes mellitus, gonadal failure (of the ovaries or testes), insufficient thyroid activity, and gastrointestinal malabsorption. This article summarizes findings in nine patients with APG I, two of whom lacked spleens (asplenism). In addition, two had gallstones and two had both asplenism and gallstones. The clinical characteristics of the patients are summarized in tabular form. Because of the splenic abnormalities, patients' lymphocytes (which normally undergo differentiation and modification in the spleen) were investigated. Three patients had elevated numbers of total lymphocytes, but the proportions of subpopulations of T cells (the cell type mediating cellular immunity) were within normal limits. Changes were seen in some subpopulations of B cells (the cell type mediating humoral immunity), but no consistent findings were reported. The report discussing the largest group (68) of APG I patients in the medical literature did not mention gallstones or asplenism. The authors of the current article present their views regarding the relationship of these findings to the disease. Splenic impairment should be suspected in APG I patients, and they should also be examined periodically for gallstones. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cases, Gallstones

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Treatment of Wegener's granulomatosis with intermittent high-dose intravenous cyclophosphamide

Article Abstract:

Wegener's granulomatosis (WG) is characterized by vasculitis (inflammation of blood vessels), granulomatous lesions of the lungs (tumors containing granular white blood cells), and kidney dysfunction. Although fatal if not treated early, WG and other systemic vasculitis disorders have been successfully treated with steroids plus daily low-dose cyclophosphamide (CP). Unfortunately, initial drug resistance occurs in 10 percent of WG patients, and significant toxicity and relapses develop in 30 percent. Intermittent high-dose CP (pulse CP) is effective and less toxic than daily low-dose CP in patients with systemic lupus erythematosus. The effectiveness and safety of pulse CP combined with steroid therapy was studied in 14 patients with WG. Although 13 patients improved initially and 7 achieved remission, 11 patients ultimately failed pulse CP therapy due to relapses or significant toxicity. Three patients sustained remissions and one patient with limited WG continued therapy. The results suggest that, at best, only one-third of patients with WG would achieve lasting remission when treated with pulse CP and steroids, according to the protocol. Possibly, modifications of the protocol might provide a better outcome. These findings indicate that daily low-dose CP plus steroids is still the treatment of choice for Wegener's granulomatosis. (Consumer Summary produced by Reliance Medical Information, Inc.)

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