High dose cyclophosphamide treatment for autoimmune disorders.

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1808-1815
Number of pages8
JournalTheScientificWorldJournal
Volume2
DOIs
StatePublished - Jun 28 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)

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