Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes
Hypereosinophilic syndrome (HES), chronic eosinophilic leukaemia (CEL) and chronic
idiopathic hypereosinophilia (CIH) are rare disorders characterized by chronic
hypereosinophilia with possible damage to various organs due to eosinophilic infiltration
and release of cytokines. The therapies of these diseases are largely unsatisfactory and
based on the use of a variety of antiproliferative drugs such as corticosteroids,
interferon-alfa, cyclosporine, vincristine or hydroxyurea. More often the responses are
transient and patients need numerous treatment lines.
In 2001 Schaller et al reported the first case of a patient with HES resistant to
conventional treatment that responded to imatinib mesylate. (Schaller, MGM 2001). After
that, many authors described cases with hypereosinophilia that achieve a rapid response to
Imatinib and in 2003 Cools et al identified a novel tyrosine kinase generated from the
fusion of the Fip1-like 1 (FIP1L1) gene to the PDGFRalfa gene associated to
The optimal dose of Imatinib in this setting of patients is still unknown; however, the
demonstration of effective and safe clinical doses in a variety of currently studied
malignant diseases, suggests that a dose of 100 mg/day increasing weekly of 100 mg/day
(maximum dose 400 mg/day), may be employed.
We designed a phase II trial to investigate the clinical anti-proliferative activity, safety
and tolerability of escalating doses of Imatinib (entry dose 100 mg/d)administered for 12
total weeks in HES, CEL and CIH patients.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Renato Bassan, MD
USC Ematologia Ospedali Riuniti di Bergamo
Italy: Ministry of Health