High-dose cyclophosphamide in multiple sclerosis patients undergoing autologous stem cell transplantation

Timothy R McGuire, Peter Gwilt, Konstantine Manouvilov, Kathleen Healey, M. M. Ursick, Richard A. Nash, Steven Z. Pavletic

Research output: Contribution to journalArticle

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Abstract

High-dose cyclophosphamide (CTX) is commonly used in preparation for autologous and allogeneic stem cell transplantation. CTX is a pro-drug, which undergoes complex oxidative metabolism with the metabolites being eliminated both renally and hepatically. In the following study, we evaluated the pharmacokinetic characteristics of high-dose CTX in three patients undergoing autologous stem cell transplantation for multiple sclerosis. The plasma concentration-time profiles for CTX and its hydroxy-metabolite were similar in multiple sclerosis patients to those reported in cancer patients undergoing stem cell transplantation. There was an increase in drug clearance after the second CTX dose indicating that the drug induced its own metabolism consistent with reports in other populations receiving high-dose CTX. One of the three patients cleared the drug slowly but this was not associated with greater toxicity. The patient with the slow clearance value and therefore highest drug exposure had stable disability scores at 2 years posttransplant compared with baseline values taken prior to transplantation. In conclusion, in this small case series, there was no indication that CTX metabolism was different than that in other populations undergoing transplantation.

Original languageEnglish (US)
Pages (from-to)279-283
Number of pages5
JournalInternational Immunopharmacology
Volume3
Issue number2
DOIs
StatePublished - Feb 2003

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Stem Cell Transplantation
Cyclophosphamide
Multiple Sclerosis
Pharmaceutical Preparations
Transplantation
Prodrugs
Population
Pharmacokinetics
Neoplasms

Keywords

  • CTX pharmacokinetics
  • Multiple sclerosis
  • Stem cell transplant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

High-dose cyclophosphamide in multiple sclerosis patients undergoing autologous stem cell transplantation. / McGuire, Timothy R; Gwilt, Peter; Manouvilov, Konstantine; Healey, Kathleen; Ursick, M. M.; Nash, Richard A.; Pavletic, Steven Z.

In: International Immunopharmacology, Vol. 3, No. 2, 02.2003, p. 279-283.

Research output: Contribution to journalArticle

McGuire, Timothy R ; Gwilt, Peter ; Manouvilov, Konstantine ; Healey, Kathleen ; Ursick, M. M. ; Nash, Richard A. ; Pavletic, Steven Z. / High-dose cyclophosphamide in multiple sclerosis patients undergoing autologous stem cell transplantation. In: International Immunopharmacology. 2003 ; Vol. 3, No. 2. pp. 279-283.
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