RESUMO
Preliminary evidence suggests that the multikinase inhibitor sorafenib has clinical activity in FLT3-ITD-positive (FLT3-ITD) acute myeloid leukemia (AML). However, the quality and sustainability of achievable remissions and clinical variables that influence the outcome of sorafenib monotherapy are largely undefined. To address these questions, we evaluated sorafenib monotherapy in 65 FLT3-ITD AML patients treated at 23 centers. All but two patients had relapsed or were chemotherapy-refractory after a median of three prior chemotherapy cycles. Twenty-nine patients (45%) had undergone prior allogeneic stem cell transplantation (allo-SCT). The documented best responses were: hematological remission in 24 patients (37%), bone marrow remission in 5 patients (8%), complete remission (with and without normalization of peripheral blood counts) in 15 patients (23%) and molecular remission with undetectable FLT3-ITD mRNA in 10 patients (15%), respectively. Seventeen of the patients without prior allo-SCT (47%) developed sorafenib resistance after a median treatment duration of 136 days (range, 56-270 days). In contrast, allo-SCT patients developed sorafenib resistance less frequently (38%) and significantly later (197 days, range 38-225 days; P=0.03). Sustained remissions were seen exclusively in the allo-SCT cohort. Thus, sorafenib monotherapy has significant activity in FLT3-ITD AML and may synergize with allogeneic immune effects to induce durable remissions.
Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Piridinas/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/metabolismo , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Estudos Retrospectivos , SorafenibeAssuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Síndrome Hipereosinofílica/tratamento farmacológico , Mutação , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Adolescente , Adulto , Idoso , Benzamidas , Doença Crônica , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Síndrome Hipereosinofílica/genética , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , SorafenibeRESUMO
Eosinophil-associated conditions, such as asthma and eosinophilic bronchitis, have been associated with chronic persistent cough, usually responding to corticosteroid therapy. This case study reports a case of persistent cough associated with gastro-oesophageal reflux (GOR) and hypereosinophilia. Treatment of GOR with proton pump inhibitors and fundoplication did not control the cough. However, high dose prednisolone, but not inhaled corticosteroids, did. The presence of the FIP1L1-PDGFRA fusion gene in myeloid cells was confirmed by fluorescence in situ hybridisation analysis using CHIC2 deletion as a surrogate marker. The cough and other disease features were subsequently suppressed by the tyrosine kinase inhibitor, imatinib. This is the first case of persistent cough caused by hypereosinophilic syndrome characterised by FIP1L1-PDGFRA fusion gene and aberrant tyrosine kinase activity.