Eosinophilia in systemic mastocytosis:: Clinical and molecular correlates and prognostic significance

Background: In a group of patients with systemic mastocytosis (SM), marked and sustained eosinophilia is detectable (SM-eo). Objective: Although the molecular defect has been defined in some cases, little is known about the impact and clinical correlates of eosinophilia. Methods: In a cohort of 63 patients with SM, we identified 9 with permanent eosinophilia (> 1500/mu L). According to the World Health Organization classification, 2 bad indolent SM, I had smoldering SM, 2 had SM with associated chronic eosinophilic leukemia (SM-CEL), and 4 had aggressive SM. Results: SM-eo was found to be associated with a significantly reduced probability of overall and event-free survival compared with SM without eosinophilia (P < .05). In the 2 patients with SM-CEL, a CHIC2 deletion was found. By contrast, no KIT mutation at codon 816 was detectable in these patients. In the other patients with SM-eo, KIT D816V was demonstrable. The 2 patients with SM-CEL had cardiomyopathy, whereas other organ systems remained largely unaffected. By contrast, in all other patients with SM-eo, organopathy, if recorded, affected the bone marrow, liver, or/and skeletal system, but not the heart, even when eosinophilia persisted for many years. Conclusions: The biochemical basis of eosinophilia in SM is variable and predictive for the type of organopathy. Clinical implications: In SM eosinophilia is of prognostic significance but is not a final diagnosis and is not invariably associated with cardiomyopathy. The latter might be restricted to cases with an associated primary eosinophilic disorder