Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a 
rare immunodeficiency disorder caused by gain-of-function mutations in the G 
protein-coupled chemokine receptor CXCR4. The CXCR4 antagonist plerixafor, which 
is approved by the US Food and Drug Administration (FDA) for stem cell 
mobilization in cancer and administered for that indication at 0.24 mg/kg, has 
been shown in short-term (1- to 2-week) phase 1 dose-escalation studies to 
correct neutropenia and other cytopenias in WHIM syndrome. However, long-term 
safety and long-term hematologic and clinical efficacy data are lacking. Here we 
report results from the first long-term clinical trial of plerixafor in any 
disease, in which 3 adults with WHIM syndrome self-injected 0.01 to 0.02 mg/kg 
(4% to 8% of the FDA-approved dose) subcutaneously twice daily for 6 months. 
Circulating leukocytes were durably increased throughout the trial in all 
patients, and this was associated with fewer infections and improvement in warts 
in combination with imiquimod; however, immunoglobulin levels and specific 
vaccine responses were not fully restored. No drug-associated side effects were 
observed. These results provide preliminary evidence for the safety and clinical 
efficacy of long-term, low-dose plerixafor in WHIM syndrome and support its 
continued study as mechanism-based therapy in this disease. The 
ClinicalTrials.gov identifier for this study is NCT00967785.