Primary hypereosinophilic sindromes and imatinib therapy: a rtrospective analysis of 38 cases

Background: Chronic myeloproliferative neoplasms with eosinophilia are rare and heterogeneus disorders characterized by eosinophil proliferation and tissue damage. The 2008 updated “Classification of Tumors of the Hematopoietic and Lymphoid Tissues” of the World Health Organization, divides this neoplasms into two major subgroups: myeloid and lymphoid neoplasms with eosinophilia associated with Platelet-derived Growth Factor Receptor (PDGFR)-a, PDGFRb or Fibroblast Growth Factor Receptor1 (FGFR1) and CEL, NOS. Low-dose imatinib is an effective therapy for myeloid neoplasms with eosinophilia and abnormalities of PDGFRa/b, and prognosis of these disease has dramatically improved. CEL, NOS remains a difficult-to treat disease with a dismal prognosis. Methods: We retrospectively evaluated data from 38 patients affected by primary eosinophilia followed at IRCCS Ca’ Granda Maggiore Hospital Foundation, Milan and Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. Results: Median age at diagnosis was 53 years (range 18-77). Seven cases presented PDGFR-a rearrangements, while 8 were diagnosed as CEL, NOS. Diagnosis were HES and HE(US) in 17 and 6 patients, respectively. Four CEL, NOS patients presented the KITM541L somatically acquired mutation. Organ damage was present in 27 patients: pruritus and cutaneous lesions occurred in 37% of cases, 32% and 12% presented various degree of pulmonary and cardiac alterations, respectively, diarrhoea and venous thrombosis were found in 5% of cases. Thirty patients received imatinib and overall response rate was 57%. Complete hematologic response (CHR) to low-dose imatinib was obtained in all patients presenting PDGFR-a rearrangements, in 57% of CEL, NOS and 31% of HES patients, respectively. After a median imatinib treatment of 3 years (range 1-9), 6-years progression-free survival was 75% and 54% for patients with PDGFR-a rearrangement and CEL, NOS, respectively. For CEL, NOS patients harbouring the KITM541L mutation and treated with low-dose imatinib, 6-years PFS was 67%. Median OS for patients receiving imatinib was 70 months. Conclusions: Our data confirm that myeloprolipherative neoplasms with eosinophilia are rare disorders presenting various clinical pictures. Low-dose imatinib is an effective therapy for cases with PDGFR-a rearrangements. Furthermore, search at diagnosis for the KITM541L in CEL, NOS patients could identify an additional subgroup of patients that may benefit from low-dose imatinib.