Reduction of Disease Activity and Disability With High-Dose Cyclophosphamide in Patients With Aggressive Multiple Sclerosis

Krishnan, Chitra; Kaplin, Adam I.; Brodsky, Robert A.; Drachman, Daniel B.; Jones, Richard J.; Pham, Dzung L.; Richert, Nancy; Pardo, Carlos A.; Yousem, David M.; Hammond, Edward R.; Quigg, Megan; Trecker, Carrilin C.; McArthur, Justin C.; Nath, Avindra; Greenberg, Benjamin; Calabresi, Peter A.; Kerr, Douglas A.

doi:10.1001/archneurol.65.8.noc80042

Cited by 79 publications

(49 citation statements)

References 36 publications

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“…High-dose cyclophosphamide is a highly immunosuppressive agent that, in addition to its successful use as a treatment for aplastic anemia [9][10][11] and other severe refractory autoimmune diseases, 14,16,21,22 has proven efficacy in allogeneic BMT as both a conditioning regimen 23 and graft-versus-host disease prophylaxis. 24 Cyclophosphamide's unique metabolism is responsible for its immunosuppressive yet stem cell-sparing properties.…”

Section: Discussionmentioning

confidence: 99%

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

Brodsky

Chen

Dorr³

et al. 2010

Blood

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105

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Severe aplastic anemia (SAA) is a lifethreatening bone marrow failure disorder that can be treated with bone marrow transplantation, immunosuppressive therapy, and high-dose cyclophosphamide. Here, we report long-term follow-up on 67 SAA patients (44 treatment-naive and 23 refractory) treated with high-dose cyclophosphamide. At 10 years, the overall actuarial survival was 88%, the response rate was 71% with the majority being complete, and the actuarial event-free survival was 58% in 44 treatmentnaive SAA patients. Patients with refractory SAA fared less well after high-dose cyclophosphamide therapy; at 10 years, overall actuarial survival, response, and actuarial event-free survival rates were 62%, 48%, and 27%, respectively. High-dose cyclophosphamide is highly effective therapy for severe aplastic anemia. Large randomized controlled trials will be necessary to establish how results of high-dose cyclophosphamide compare with either bone marrow transplantation or standard immunosuppressive regimens, such as antithymocyte globulin and cyclosporine. (Blood. 2010;

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Section: Discussionmentioning

confidence: 99%

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

Brodsky

Chen

Dorr³

et al. 2010

Blood

Self Cite

105

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“…Although approaches differ we have most typically given an in-hospital induction regimen with 3-5 days of recurrent therapy. A report by Krishnan et al [33] describes an induction regimen of 50 mg/kg/day of cyclophosphamide for 4 days with granulocyte colony-stimulating factor to rescue neutrophils. Enrolled patients were required to have consecutive active MRIs, at least 1 clinical exacerbation in the year prior to high-dose cyclophosphamide treatment, or a sustained increase of 1 point or higher on the Expanded Disability Status Scale (EDSS) in the preceding year.…”

Section: Inductionmentioning

confidence: 99%

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

et al. 2013

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“…96 A more recent trial demonstrated the benefit of high-dose cyclophosphamide (50 mg/kg per d for 4 consecutive days, followed by granulocyte colony-stimulating factor 6 days after completion) in 9 patients with aggressive RRMS, 8 of whom had not responded to conventional steroid therapy. 97 Although this study was conducted in patients who had clinical exacerbations between 6 and 12 months prior to enrollment, and actually excluded patients who had a flare in the 3 months prior to cyclophosphamide administration, one might extrapolate that cyclophosphamide could be utilized as a rescue treatment for acute fulminant relapses. Safety concerns with the use of short-term high-dose cyclophosphamide monotherapy in patients with MS include neutropenia and infection.…”

Section: Acute Treatment Of Cis-what Every Neurohospitalist Needs To mentioning

confidence: 99%

Updates on Clinically Isolated Syndrome and Diagnostic Criteria for Multiple Sclerosis

Marcus

Waubant

2012

The Neurohospitalist

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Clinically isolated syndrome (CIS) is a central nervous system demyelinating event isolated in time that is compatible with the possible future development of multiple sclerosis (MS). Early risk stratification for conversion to MS helps with treatment decisions. Magnetic resonance imaging (MRI) is currently the most useful tool to evaluate risk. Cerebrospinal fluid studies and evoked potentials may also be used to assess the likelihood of MS. Four clinical trials evaluating the benefits of either interferon b (IFN-b) or glatiramer acetate (GA) within the first 3 months after a high-risk CIS demonstrate decreased rates of conversion to clinically definite MS (CDMS) and a lesser degree of MRI progression with early treatment. In the 3-, 5-, and 10-year extension studies of 2 formulations of IFN-b, the decreased conversion rate to CDMS remained meaningful when comparing early treatment of CIS to treatment delayed by a median of 2 to 3 years. Diagnostic criteria have been developed based on the clinical and MRI follow-up of large cohorts with CIS and provide guidance on how to utilize clinical activity in combination with radiographic information to diagnose MS. The most recent 2010 McDonald criteria simplify requirements for dissemination in time and space and allow for diagnosis of MS from a baseline brain MRI if there are both silent gadolinium-enhancing lesions and nonenhancing lesions on the same imaging study. The diagnostic criteria for MS require special consideration in children at risk for acute disseminated encephalomyelitis (ADEM), in older adults who may have small vessel ischemic disease, and in ethnic groups that more commonly develop neuromyelitis optica (NMO).

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Reduction of Disease Activity and Disability With High-Dose Cyclophosphamide in Patients With Aggressive Multiple Sclerosis

Cited by 79 publications

References 36 publications

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

Updates on Clinically Isolated Syndrome and Diagnostic Criteria for Multiple Sclerosis

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