FIP1L1-PDGFRA Positive Secondary Acute Myeloid Leukemia.

Abstract

The FIP1L1-PDGFRA positive myeloproliferative syndrome (MPS) represents a distinct clinicobiological entity with constitutively enhanced tyrosine kinase activity of the fusion protein and excellent response to treatment with imatinib. Most patients are initially diagnosed as idiopathic hypereosinophilic syndrome or chronic eosinophilic leukemia (CEL). A prominent clinical feature besides eosinophilia is the male predominance. However, the natural clinical course remains to be elucidated. Here we report on five male FIP1L1-PDGFRA positive patients (median age 58, range 46–64 years) with various subtypes of acute myeloid leukemia (AML) according to the FAB classification (M0, n=2; M2, n=1; M4eo, n=1; acute eosinophilic leukemia, n=1). All patients had a history of pronounced eosinophilia for a median interval of 6 mo (range 2–186) indicating the presence of a CML-like chronic phase disease evolving to blast crisis or secondary AML. One patient relapsed six years after conventional chemotherapy of a secondary FIP1L1-PDGFRA positive eosinophilia-associated AML M0 with typical features of CEL. Three patients had additional cytogenetic aberrations at diagnosis of AML similar to those frequently observed during clonal evolution of CML (trisomy 8, n=2; trisomy 9, n=1). All five patients received imatinib (100–300 mg/day) for a median time of 12 mo (range 1–23); three patients as monotherapy, one patient after one course and another patient after two courses of intensive chemotherapy. Three AML patients have been treated for more than 3 mo (12+, 18+, and 23+ mo) and are currently free of relapse. All three patients achieved a rapid complete hematological remission, defined as a complete clearance of blasts, normalization of peripheral blood and bone marrow eosinophil count, and a complete molecular remission 4, 5, and 14 mo, respectively, after start of treatment as determined by nested RT-PCR for the FIP1L1-PDGFRA transcript. In all cases treatment with imatinib was well tolerated. We conclude that the occurrence of the FIP1L1-PDGFRA fusion gene seems to be associated with a chronic phase disease which may progress to secondary AML. Therefore, all patients presenting with an eosinophilia-associated AML and normal karyotype should be screened for the cytogenetically invisible FIP1L1-PDGFRA fusion gene by RT-PCR and/or fluorescence in situ hybridization, in addition to the commoner CBFB-MYH11 fusion. Patients with a FIP1L1-PDGFRA positive MPS are excellent candidates for treatment with imatinib even if they present with secondary AML.