Plerixafor for the Treatment of WHIM Syndrome

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.).

Keywords

Benzylamines Bone Marrow / pathology* Bone Marrow Examination Cyclams Fatal Outcome Heterocyclic Compounds / therapeutic use* Immunologic Deficiency Syndromes / drug therapy* Immunologic Deficiency Syndromes / pathology Middle Aged Neoplasms, Squamous Cell / drug therapy Neoplasms, Squamous Cell / genetics Phenotype Primary Immunodeficiency Diseases Primary Myelofibrosis / drug therapy Primary Myelofibrosis / pathology Receptors, CXCR4 / antagonists & inhibitors* Receptors, CXCR4 / genetics Warts / drug therapy* Warts / pathology HDE INF PED