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High Dose Cyclophosphamide Treatment for Autoimmune Disorders

High-dose cyclophosphamide (200 mg/kg) was initially developed as a conditioning regimen for allogeneic bone marrow transplantation. Recently, high-dose cyclophosphamide without bone marrow transplantation has been employed as a method to induce durable treatment-free remissions in severe aplastic a...

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Autor principal: Brodsky, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: TheScientificWorldJOURNAL 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009530/
https://www.ncbi.nlm.nih.gov/pubmed/12806171
http://dx.doi.org/10.1100/tsw.2002.863
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author Brodsky, Robert A.
author_facet Brodsky, Robert A.
author_sort Brodsky, Robert A.
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description High-dose cyclophosphamide (200 mg/kg) was initially developed as a conditioning regimen for allogeneic bone marrow transplantation. Recently, high-dose cyclophosphamide without bone marrow transplantation has been employed as a method to induce durable treatment-free remissions in severe aplastic anemia and a variety of other severe autoimmune disorders. The premise underlying this approach is that high-dose cyclophosphamide is maximally immunosuppressive, but not myeloablative. Early hematopoietic stem cells are spared the cytotoxicity of cyclophosphamide because of their high levels of aldehyde dehydrogenase, an enzyme that confers resistance to the drug. Conversely, autoimmune effector cells (T cells, B cells, and NK cells) are exquisitely sensitive to high-dose cyclophosphamide because of their relatively low levels of aldehyde dehydrogenase. Intensive investigation is underway to determine which autoimmune disorders will most benefit and where in the natural history of these diseases to employ this rapidly developing therapy.
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spelling pubmed-60095302018-07-04 High Dose Cyclophosphamide Treatment for Autoimmune Disorders Brodsky, Robert A. ScientificWorldJournal Mini-Review Article High-dose cyclophosphamide (200 mg/kg) was initially developed as a conditioning regimen for allogeneic bone marrow transplantation. Recently, high-dose cyclophosphamide without bone marrow transplantation has been employed as a method to induce durable treatment-free remissions in severe aplastic anemia and a variety of other severe autoimmune disorders. The premise underlying this approach is that high-dose cyclophosphamide is maximally immunosuppressive, but not myeloablative. Early hematopoietic stem cells are spared the cytotoxicity of cyclophosphamide because of their high levels of aldehyde dehydrogenase, an enzyme that confers resistance to the drug. Conversely, autoimmune effector cells (T cells, B cells, and NK cells) are exquisitely sensitive to high-dose cyclophosphamide because of their relatively low levels of aldehyde dehydrogenase. Intensive investigation is underway to determine which autoimmune disorders will most benefit and where in the natural history of these diseases to employ this rapidly developing therapy. TheScientificWorldJOURNAL 2002-06-28 /pmc/articles/PMC6009530/ /pubmed/12806171 http://dx.doi.org/10.1100/tsw.2002.863 Text en Copyright © 2002 Robert A. Brodsky. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Mini-Review Article
Brodsky, Robert A.
High Dose Cyclophosphamide Treatment for Autoimmune Disorders
title High Dose Cyclophosphamide Treatment for Autoimmune Disorders
title_full High Dose Cyclophosphamide Treatment for Autoimmune Disorders
title_fullStr High Dose Cyclophosphamide Treatment for Autoimmune Disorders
title_full_unstemmed High Dose Cyclophosphamide Treatment for Autoimmune Disorders
title_short High Dose Cyclophosphamide Treatment for Autoimmune Disorders
title_sort high dose cyclophosphamide treatment for autoimmune disorders
topic Mini-Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009530/
https://www.ncbi.nlm.nih.gov/pubmed/12806171
http://dx.doi.org/10.1100/tsw.2002.863
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