title: The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome.
abstract: Mutations in CXCR4 cause severe leukopenia in myelokathexis or WHIM syndrome. Plerixafor inhibits binding of CXCR4 to its ligand CXCL12. We investigated the effects of plerixafor (0.04 to 0.24 mg/kg) administered at 2-4 day intervals in 6 patients. Outcome measures were the patients' complete blood cell counts, CD34(+) cell counts and lymphocyte subtypes compared with 5 normal subjects similarly treated with plerixafor. All patients showed prompt leukocytosis with maximum blood neutrophils and lymphocytes at 6-12 hours. Blood neutrophils peaked at 6-12 hours, increasing from a mean baseline of 0.4 ± 0.1 × 10⁹/L, to mean peak of 4.5 ± 0.78 × 10⁹/L. Lymphocytes also increased; the greatest increase was in B cells (CD19(+) cells), a > 40-fold increase over baseline at the 0.08 mg/kg dose. None of the patients experienced any significant adverse effects. Plerixafor is a promising therapy for this condition.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA. dcdale@uw.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Dale
authors.forename: Audrey Anna
authors.initials: AA
authors.lastname: Bolyard
authors.forename: Merideth L
authors.initials: ML
authors.lastname: Kelley
authors.forename: Ernest C
authors.initials: EC
authors.lastname: Westrup
authors.forename: Vahagn
authors.initials: V
authors.lastname: Makaryan
authors.forename: Andrew
authors.initials: A
authors.lastname: Aprikyan
authors.forename: Brent
authors.initials: B
authors.lastname: Wood
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001596:Benzylamines; D001855:Bone Marrow Diseases / Q000188:drug therapy / Q000473:pathology; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D042381:Granulocyte Precursor Cells / Q000187:drug effects* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007970:Leukopenia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000081207:Primary Immunodeficiency Diseases; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics; D014860:Warts / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; C527276:CXCR4 protein, human; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor