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.

Figures

Figure 1

Absolute leukocyte counts after various doses of plerixafor in normal controls and patients. Serial absolute leukocyte counts (mean ± SEM) measured 0, 1, 3, 6, 9 and 24 hours after various doses of plerixafor in normal control subjects (n = 5) and patients (n = 6).

Figure 2

Comparisons of mean absolute neutrophil, monocyte and CD34+ cell counts and various lymphocyte subpopulations for normal controls and patients after plerixafor. Comparisons shown are mean (± SEM) absolute counts for normal control subjects (n = 5) and patients (n = 6) at baseline and 6 hours after 0.8 mg/kg of plerixafor. Differences from baseline to 6 hours for the patients were compared using Student t test: * indicates P < .05; **P < .01; ***P < .001. The patients and controls were compared using the log ratio t test: *P < .05; **P < .01; ***P < .001.