Skip NavigationSkip to Content
Return Return to Search Results

The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome

  1. Author:
    McDermott, D. H.
    Liu, Q.
    Ulrick, J.
    Kwatemaa, N.
    Anaya-O'Brien, S.
    Penzak, S. R.
    Oliveira, J.
    Priel, D. A. L.
    Kelly, C.
    Garofalo, M.
    Littel, P.
    Marquesen, M. M.
    Hilligoss, D.
    DeCastro, R.
    Fleisher, T. A.
    Kuhns, D. B.
    Malech, H. L.
    Murphy, P. M.

  2. Author Address

    [McDermott, DH; Liu, Q; Murphy, PM] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Ulrick, J; Kwatemaa, N; Anaya-O'Brien, S; Kelly, C; Garofalo, M; Littel, P; Marquesen, MM; Hilligoss, D; DeCastro, R; Malech, HL] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Penzak, SR] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. [Oliveira, J; Fleisher, TA] NIH, Ctr Clin, Div Lab Med, Bethesda, MD 20892 USA. [Priel, DAL; Kuhns, DB] NCI, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21701 USA.;McDermott, DH (reprint author), 9000 Rockville Pike,Bldg 10,Rm 11N107, Bethesda, MD 20892 USA;dmcdermott@nih.gov
    1. Year: 2011
    2. Date: Nov
  2. Journal: Blood
    1. 118
    2. 18
    3. Pages: 4957-4962
  4. Type of Article: Article
  5. ISSN: 0006-4971
  1. Abstract:

    WHIM syndrome is a rare congenital immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (neutropenia because of impaired egress from the BM); most patients also have severe panleukopenia. Because WHIM syndrome is caused by mutations in the chemokine receptor CXCR4 that result in increased agonist-dependent signaling, we hypothesized that the CXCR4 antagonist plerixafor (Mozobil [Genyzme Corporation], AMD3100), might be an effective treatment. To test this, we enrolled 3 unrelated adult patients with the most common WHIM mutation, CXCR4(R334X), in a phase 1 dose-escalation study. Plerixafor increased absolute lymphocyte, monocyte, and neutrophil counts in blood to normal without significant side effects in all 3 patients. Peak responses occurred at 3-12 hours after injection and waned by 24 hours after injection which tracked the drug's pharmacokinetics. All 3 cell types increased in a dose-dependent manner with the rank order of responsiveness absolute lymphocyte > monocyte > neutrophil. These data provide the first pharmacologic evidence that panleukopenia in WHIM syndrome is caused by CXCL12-CXCR4 signaling-dependent leukocyte sequestration, and support continued study of plerixafor as mechanism-based therapy in this disease. This study is registered at http://www.clinicaltrials.gov as NCT00967785. (Blood. 2011;118(18):4957-4962)

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1182/blood-2011-07-368084
  3. View record in Web of Science®
  4. WOS: 000296714500025

Library Notes

  1. Fiscal Year: FY2011-2012
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel