RESUMO
BACKGROUND: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES). METHODS: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 × 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study. RESULTS: Overall, imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36). CONCLUSIONS: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.
Assuntos
Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Fenótipo , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Medula Óssea/patologia , Eosinófilos , Feminino , Seguimentos , Humanos , Síndrome Hipereosinofílica/genética , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Resultado do Tratamento , Adulto Jovem , Fatores de Poliadenilação e Clivagem de mRNA/genéticaRESUMO
Over a five-year period (1995-1999) the Microbial Diseases Laboratory received 34 strains of E. coli O157:H7 each with a single aberrant biochemical property. In addition, 27 O157 strains with negative or delayed motility were noted during the same time period. These observations suggest that there may be an increased likelihood to misdiagnose O157:H7 infections using commercial systems in the future due to increasing phenotypic variability.