Plerixafor for the Treatment of WHIM Syndrome

Overview

Journal N Engl J Med

Specialty General Medicine

Date 2019 Jan 10

PMID 30625055

Citations 39

Authors

David H McDermott

Diana V Pastrana

Katherine R Calvo

Stefania Pittaluga

Daniel Velez

Elena Cho

Qian Liu

Hugh H Trout 3rd

Joao F Neves

Pamela J Gardner

David A Bianchi

Elizabeth A Blair

Emily M Landon

Susana L Silva

Christopher B Buck

Philip M Murphy

Affiliations

Soon will be listed here.

Abstract

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Myelokathexis is neutropenia caused by neutrophil retention in bone marrow. Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia. In this investigator-initiated, open-label study, three severely affected patients with WHIM syndrome who could not receive G-CSF were treated with low-dose plerixafor, a CXCR4 antagonist, for 19 to 52 months. Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus-associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly. Adverse events were mainly infections attributable to the underlying immunodeficiency. One patient died from complications of elective reconstructive surgery. (Funded by the National Institutes of Health.).

Citing Articles

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CXCR4 antagonism ameliorates leukocyte abnormalities in a preclinical model of WHIM syndrome.

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PMID: 39588369 PMC: 11586337. DOI: 10.3389/fimmu.2024.1468823.

Increased Susceptibility of WHIM Mice to Papillomavirus-induced Disease is Dependent upon Immune Cell Dysfunction.

Wang W, Pope A, Ward-Shaw E, Buehler D, Bachelerie F, Lambert P PLoS Pathog. 2024; 20(9):e1012472.

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