| High-dose cyclophosphamide without stem cell rescue in 207 patients with aplastic anemia and other autoimmune diseases. | |
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MedLine Citation:
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PMID: 21358440 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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High-dose cyclophosphamide has long been used as an anticancer agent, a conditioning regimen for hematopoietic stem cell transplantation, and a potent immunosuppressive agent in autoimmune diseases including aplastic anemia. High-dose cyclophosphamide is highly toxic to lymphocytes but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase, the major mechanism of cyclophosphamide inactivation. High-dose cyclophosphamide therapy induces durable remissions in most patients with acquired aplastic anemia. Moreover, high-dose cyclophosphamide without hematopoietic stem cell rescue has shown activity in a variety of other severe autoimmune diseases. Here we review the history of cyclophosphamide as it applies to aplastic anemia and other autoimmune diseases. We include historical data from early patients treated for aplastic anemia as well as data from 140 patients from an observational retrospective study in a single tertiary care hospital. This latter component was designed to assess the safety and efficacy of high-dose cyclophosphamide therapy without stem cell rescue in patients with refractory autoimmune diseases. We analyzed the 140 patients with severe, progressive autoimmune diseases treated. All patients discussed here received cyclophosphamide, 50 mg/kg per day for 4 consecutive days. Response, relapse, and overall survival were measured. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune-modulating drugs. Relapse was defined as worsening disease activity and/or a requirement for an increase in dose of, or administration of new, immunosuppressive medications. Hematologic recovery occurred in all patients. The overall response rate was 94%, and 44% of those patients remained progression free with a median follow-up of 36 months (range, 1-120 mo) for the 140 patients analyzed together. The overall actuarial and event-free survival across all diseases at 60 months was 90.7% and 20.6%, respectively. High-dose cyclophosphamide without stem cell rescue is well tolerated and induces a high rate of remission in severe autoimmune diseases. |
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Authors:
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Amy E DeZern; Michelle Petri; Daniel B Drachman; Doug Kerr; Edward R Hammond; Jeanne Kowalski; Hua-Ling Tsai; David M Loeb; Grant Anhalt; Fredrick Wigley; Richard J Jones; Robert A Brodsky |
Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Medicine Volume: 90 ISSN: 1536-5964 ISO Abbreviation: Medicine (Baltimore) Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-02 Completed Date: 2011-04-26 Revised Date: 2013-05-26 |
Medline Journal Info:
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Nlm Unique ID: 2985248R Medline TA: Medicine (Baltimore) Country: United States |
Other Details:
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Languages: eng Pagination: 89-98 Citation Subset: AIM; IM |
Affiliation:
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Division of Hematology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Anemia, Aplastic / drug therapy* Antineoplastic Agents / administration & dosage, adverse effects, therapeutic use* Autoimmune Diseases / drug therapy* Child Child, Preschool Cyclophosphamide / administration & dosage, adverse effects, therapeutic use* Dose-Response Relationship, Drug Female Humans Immunosuppressive Agents / administration & dosage, adverse effects, therapeutic use* Infant Male Middle Aged Recurrence Survival Analysis Time Factors Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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5K12 HL087169-05/HL/NHLBI NIH HHS; K12 HL087169-05/HL/NHLBI NIH HHS; P01 CA070970-10A1/CA/NCI NIH HHS; P01CA70970/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Immunosuppressive Agents; 50-18-0/Cyclophosphamide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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