Molecular characterization of paediatric idiopathic hypereosinophilia.

Summary Hypereosinophilic syndromes (HES) include a group of heterogeneous diseases characterized by the persistent increase of the number of eosinophils in blood and bone marrow. Few cases of paediatric hypereosinophilia (pHES) have been described in the literature. Early identification of pHES that may evolve towards a lymphomyeloproliferative disease is relevant in light of prognostic and therapeutic implications. Molecular features of 10 pHES patients were analysed at presentation and during their clinical outcome, including analysis of BCR-ABL and FIP1L1/PDGFRA fusion genes, quantitation of Wilm's tumour suppressor gene copy number and clonality of T-cell receptor and immunoglobulin heavy chain (IgH). All patients had normal karyotype and germ line T-cell receptor configuration. Five children showed IgH clonality at presentation: of these, two developed a B non-Hodgkin lymphoma and a B-lineage acute lymphocytic leukaemia at six and 12 months, respectively, two spontaneously reverted to a polyclonal IgH profile during the follow-up, and the last one persisted with pHES without B-clonal evolution after 19 months. One patient had a PDGFRA/FIP1L1 fusion and achieved hematologic and molecular remission after imatinib therapy. IgH rearrangement was observed to be a frequent molecular feature of pHES in children and may precede B-cell clonal expansion and evolution into B-cell malignancies.