Dasatinib-induced response in a rare case of chronic lymphocytic leukaemia associated with chronic myeloid leukaemia.

摘要

Dasatinib, a second-generation Abl inhibitor developed to overcome imatinib resistance in chronic myeloid leukaemia (CML), has been recently found to sensitize in vitro chronic lymphocytic leukaemia (B-CLL) cell lines to fludarabine (Veldurthy et al, 2008). Furthermore, in B-CLL, dasatinib synergistically sensitizes primary lymphocytes to chlorambucil and fludarabine (Amrein et al, 2008), prevents CD40-mediated drug resistance (Hallaert et al, 2008) and induces a high proapoptotic response in primary lymphocytes obtained from patients with aggressive disease (Amrein et al, 2008; Veldurthy et al, 2008). Although the effects of dasatinib on B-CLL have been clearly demonstrated in vitro, few data are currently available in vivo, with the exception of two very preliminary reports regarding ongoing phase II studies in relapsed/refractory patients (Amrein et al, 2007; Garg et al, 2008) and of the recently published case of a dasatinib-responsive B-CLL in a patient treated for a coexisting relapsed gastrointestinal stromal tumour (GIST) (Pitini et al, 2009).