Leukocytosis, Monocytosis, and Eosinophilia in Systemic Mastocytosis: Analysis of Phenotype, Genetics and Prognosis in 596 Patients From the GREM Registry.

Abstract

Leukocytosis, monocytosis, and eosinophilia (L/M/E) are recurrent findings in systemic mastocytosis (SM). To investigate the prevalence of L/M/E in SM and assess their association with clinical phenotype, mutational profile, and overall survival (OS) in advanced SM (AdvSM). Within the German Registry on Disorders of Eosinophilia and Mast Cells, 596 patients with SM (91% KIT D816V positive; 270 AdvSM, 326 non-AdvSM) were analyzed for L/M/E. In comparison with non-AdvSM, patients with AdvSM had significantly higher leukocyte (median 9.4 vs 6.9 × 10⁹/L), monocyte (median 0.7 vs 0.5 × 10⁹/L), and eosinophil counts (median 0.3 vs 0.1 × 10⁹/L; all P < .001), with the highest counts (leukocytes: 10.2 × 10⁹/L, monocytes: 0.9 × 10⁹/L, and eosinophils: 0.3 × 10⁹/L; all P < .001) being observed in SM with associated hematologic neoplasm (SM-AHN). High counts of L/M/E correlated with an increased number of additional somatic mutations (P = .012, P < .001, and P = .020), with monocytosis being specially associated with mutations in ASXL1 (odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.5-5.8), SRSF2 (OR: 2.2; 95% CI: 1.2-4.0), and TET2 (OR: 2.2; 95% CI: 1.2-4.0). In AdvSM, optimal OS cutoff values based on maximally selected rank statistics were ≥16.8 × 10⁹/L for leukocytosis (median OS: 1.6 vs 4.7 years, P < .001), ≥1.1 × 10⁹/L for monocytosis (2.9 vs 4.8 years, P < .001), and ≥1.5 × 10⁹/L for eosinophilia (1.7 vs 5.0 years, P < .001). Monocytosis and/or eosinophilia defined a 3-tiered risk model (median OS: 1.60 vs 3.04 vs 6.94 years, P < .001). Elevated counts of L/M/E are indicative of AdvSM and within AdvSM associated with additional somatic mutations, a subtype of SM-AHN and poor prognosis.