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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2004-7-29
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pubmed:abstractText |
Donor T cells activated by recipient alloantigens cause graft-versus-host disease (GVHD) after hematopoietic cell transplantation. Activated T cells express CD25, among other components of the interleukin-2 receptor. We conducted a phase I/II study to determine whether administration of CD25-specific antibody conjugated to ricin toxin A could reduce the risk of grade III or IV GVHD after marrow transplantation from HLA-matched unrelated donors. All patients received methotrexate and cyclosporine after the transplantation. The immunotoxin was given to 36 patients for 4 consecutive days beginning approximately 36 hours after the marrow infusion was completed. Fourteen (40%) of the 35 patients who could be evaluated developed grade III or IV GVHD. In a contemporaneous population of 121 patients who received marrow from HLA-matched unrelated donors and were given methotrexate and cyclosporine without the immunotoxin, the incidence of grades III and IV GVHD was 24%. Cyclosporine blocked the induction of CD25 expression on alloactivated T cells in vitro but had no detectable effect on CD25 expression by T-regulatory cells. Taken together, these results are consistent with the hypothesis that cyclosporine protected alloactivated donor T cells from the effects of the immunotoxin, whereas the CD25+ T-regulatory cells remained susceptible, causing an unexpected exacerbation of acute GVHD.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1083-8791
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pubmed:author |
pubmed-author:AnasettiClaudioC,
pubmed-author:AppelbaumFrederick RFR,
pubmed-author:DeegJoachimJ,
pubmed-author:GhetieVictorV,
pubmed-author:GooleyTedT,
pubmed-author:HansenJohn AJA,
pubmed-author:MartinPaul JPJ,
pubmed-author:NashRichard ARA,
pubmed-author:OKANN,
pubmed-author:PetersdorfEffie WEW,
pubmed-author:SchindlerJohnJ,
pubmed-author:StorbRainerR,
pubmed-author:VitettaEllen SES
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
552-60
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15282533-Adult,
pubmed-meshheading:15282533-Antibodies, Monoclonal,
pubmed-meshheading:15282533-Bone Marrow Transplantation,
pubmed-meshheading:15282533-Cyclosporine,
pubmed-meshheading:15282533-Female,
pubmed-meshheading:15282533-Flow Cytometry,
pubmed-meshheading:15282533-Graft vs Host Disease,
pubmed-meshheading:15282533-HLA Antigens,
pubmed-meshheading:15282533-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:15282533-Humans,
pubmed-meshheading:15282533-Immunoconjugates,
pubmed-meshheading:15282533-Intestines,
pubmed-meshheading:15282533-Leukemia,
pubmed-meshheading:15282533-Liver,
pubmed-meshheading:15282533-Lymphocyte Activation,
pubmed-meshheading:15282533-Lymphocyte Culture Test, Mixed,
pubmed-meshheading:15282533-Lymphocyte Depletion,
pubmed-meshheading:15282533-Lymphoma,
pubmed-meshheading:15282533-Male,
pubmed-meshheading:15282533-Middle Aged,
pubmed-meshheading:15282533-Patient Selection,
pubmed-meshheading:15282533-Receptors, Interleukin-2,
pubmed-meshheading:15282533-Ricin,
pubmed-meshheading:15282533-Skin,
pubmed-meshheading:15282533-Survival Rate,
pubmed-meshheading:15282533-T-Lymphocytes,
pubmed-meshheading:15282533-Tissue Donors,
pubmed-meshheading:15282533-Transplantation, Homologous
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pubmed:year |
2004
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pubmed:articleTitle |
Evaluation of a CD25-specific immunotoxin for prevention of graft-versus-host disease after unrelated marrow transplantation.
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pubmed:affiliation |
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. pmartin@fhcrc.org
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Clinical Trial, Phase II,
Clinical Trial, Phase I
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