Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study

Mantia, L. La; Eoli, Marica; Salmaggi, Andrea; Torri, Valter; Milanese, C.

doi:10.1007/bf03028809

Cited by 15 publications

(5 citation statements)

References 17 publications

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“…La Mantia et al reported in 30 progressive patients a better response in relapsing-progressive patients and in those receiving induction plus boosters (600 mg/m 2 ) every 2 months for 12 months. 55 Manova et al reported improved responses on disability at 12 months in 70 patients with acute relapses treated with a 3-month course of cyclophosphamide plus methylprednisolone versus methylprednisolone clone. 51 With the widespread use of beta-interferon and glatiramer acetate, physicians have been confronted with refractory patients and have reported positive results following treatment with cyc loph os ph amide in op en-label studies.…”

Section: The Canadian Cooperative Study and The Kaiser Studymentioning

confidence: 99%

Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects

2002

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Cyclophosphamide is an alkylating agent used to treat malignancies and immune-mediated inflammatory non-malignant processes such as lupus nephritis and immune-mediated neuropathies. It has been studied as a treatment for multiple sclerosis (MS) for the past 30 years and is used by physicians in selected cases of progressive or worsening MS. Review of published reports suggests that it is efficacious in cases of worsening MS that have an inflammatory component as evidenced by relapses and/or gadolinium (Gd)-enhancing lesions on magnetic resonance imaging (MRI) or in patients in earlier stages of disease where inflammation predominates over degenerative processes in the central nervous system (CNS). There is no evidence of efficacy in primary progressive MS or later stages of secondary progressive MS. Although a general immunosuppressant that affects both T- and B-cell function, cyclophosphamide has selective immune effects in MS by suppressing IL-12 and Th1-type responses and enhancing Th2/Th3 responses (IL-4, IL-10, TGF-beta; eosinophils in peripheral blood). Side effects include nausea, alopecia, infertility, bladder toxicity and risk of malignancy. The most commonly used regimens involve every 4- to 8-week outpatient i.v. pulse therapy given with or without corticosteroids and are usually well-tolerated by patients. Cyclophosphamide is currently used in patients whose disease is not controlled by beta-interferon or glatiramer acetate and those with rapidly worsening MS.

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Section: The Canadian Cooperative Study and The Kaiser Studymentioning

confidence: 99%

Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects

2002

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“…There was no statistically significant difference in clinical results for SPMS and PPMS, although the numbers of PPMS patients were small in each study. The percentage of patients worsening in the La Mantia et al study [26] is higher than one finds in natural history studies in MS [29]. In the Hohol et al study [27], patients who improved had a progressive course for a shorter time then those who did not improve.…”

Section: Cyclophosphamidementioning

confidence: 71%

“…In the La Mantia et al study, 10 of 53 (19%) of patients withdrew during the 1 year of treatment [26]. In the Hohol et al study, 22 of 95 (23%) of patients withdrew in year one, and 47 of 95 (49%) withdrew in year two [27].…”

Section: Cyclophosphamidementioning

confidence: 92%

“…In the past 3 years, there have been three reports describing the results of open-label cyclophasphomide (CP) use in patients with active MS [26][27][28]. These studies included patients with RRMS, SPMS with continuing relapses, SPMS without relapses, PPMS, and PRMS.…”

Section: Cyclophosphamidementioning

confidence: 99%

“…La Mantia et al [26] compared three different regimens. Group 1 received CP, 300 mg/m 2 /d intravenously (IV) for 9 days (induction) followed by pulses of CP, 600 mg/m 2 IV every 2 months for 1 year.…”

Section: Cyclophosphamidementioning

confidence: 99%

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Immunologic therapy for secondary and primary progressive multiple sclerosis

Myers

2001

Curr Neurol Neurosci Rep

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Multiple sclerosis (MS) is generally considered an immune-mediated demyelinating disease, and treatments designed to modify the course of MS are immunosuppressive or immunomodulatory. Although most people with MS have a relapsing-remitting course initially, the majority will eventually experience a more gradual decline in neurologic function, termed secondary progressive MS. Some patients have gradual worsening from the beginning, termed primary progressive MS. Recent pathologic studies have revealed that axonal injury and neuronal degeneration are much more prominent in MS than previously recognized, and may be the explanation for the gradual decline in neurologic function that characterizes progressive MS. The results of several clinical trials in MS indicate that suppression of the immune-mediated inflammation may decrease the relapse rate in MS, but not stop the progressive loss of neurologic function. There are many promising approaches to this clinical dilemma, but none has been proven to be effective in stopping or retarding progressive MS. More well-designed, controlled, blinded, randomized clinical trials are needed to test these putative therapies. In the mean time, we should avoid subjecting patients to potentially dangerous and unproven regimens.

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