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/μL). According to the World Health Organization classification, 2 had indolent SM, 1 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 (SM-CEL).

Key words: Mastocytosis, eosinophilia, targets, KIT D816V, FIP1L1/PDGFRα

Abbreviations used: AHNMD, Associated clonal hematologic non–mast cell lineage disease, ASM, Aggressive systemic mastocytosis, CEL, Chronic eosinophilic leukemia, CMML, Chronic myelomonocytic leukemia, FISH, Fluorescence in situ hybridization, HES, Hypereosinophilic syndrome, ISM, Indolent systemic mastocytosis, MC, Mast cell, MCL, Mast cell leukemia, SM, Systemic mastocytosis, SM-eo, Systemic mastocytosis with eosinophilia, SSM, Smoldering systemic mastocytosis, WHO, World Health Organization