SP29 | A RARE MYELOPROLIFERATIVE DISEASE: CHRONIC EOSINOPHILIC LEUKEMIA, NEW GENETIC FEATURES?

Chronic Eosinophilic Leukemia (CEL) is a rare chronic myeloproliferative disease (MPN) characterized by a sustained clonal proliferation of eosinophilic precursor leading to persistent hypereosinophilia in blood, bone marrow and peripheral tissues. The rarity of the disease and its highly variable presentation make diagnosis difficult and experience comes only from few case reports. CEL lacks specific genetic aberrations and often presents variants of genes commonly mutated in MPN such as ASXL1, TET2, EZH2 and DNMT3A while SRSF2 mutations are reported as additional in CEL cases. Mutated CSF3R and SETBP1 are often seen in chronic neutrophilic leukemia (CNL) but have not been reported in CEL. To the best of our knowledge this is the first case report of CSF3R, SETBP1 and SRSF2 mutated CEL. We report a case of a 63-years-old man admitted to the Hematology Department for fatigue, B symptoms, eosinophilic leukocytosis (WBC 141600 mm3 with 79300 mm3 eosinophils) and splenomegaly. At the bone marrow smear: megakaryocytic and erythroid dysplasia, eosinophilic hyperplasia (55%), blasts 2%. FISH analysis was negative for BCR::ABL1, PDGFRα and β, JAK2 rearrangements; NGS analysis identified CSF3R(T618I), SRSF2(P95H) and SETBP1(G870S) mutations confirming clonality. KITD816V and M54IL were excluded. After excluding secondary/ reactive hypereosinophilia, according to WHO 5th edition and ICC of eosinophilic disorders, diagnosis of CEL was made. The patient started hydroxyurea and steroid therapy with progressive decline in leukocyte count. The clinical course was complicated by the occurrence of a left elbow painful ulcer, site of disease confirmed by cytological and NGS investigation, which requested intravenous antibiotic therapy and Vacuum Assisted Closure therapy. NGS study of bone marrow blood at onset, after one month of therapy and on wound exudate showed a decrease in variant allele frequency from 17% to 7% for CSF3R mutation and stability of SRSF2 and SETBP1 allelic burden suggesting the presence of two different clones. There are only few reports about CSF3R, SRSF2 and SETBP1 mutations and all connected to CNL and chronic myelomonocytic leukemia. Few scientific publications exist regarding the presence of these mutations and their significance in CEL. To date, the clinical impact of these mutations and eventually others in CEL is unknown; more in-depth studies would be needed to confirm the pathogenetic, clinical, prognostic and/or therapeutic impact in CEL.