RESUMO
AIMS: To examine the efficacy and safety of pegfilgrastim in patients with congenital neutropenia (CN). METHODS: Seventeen patients enrolled in the French Severe CN Register received pegfilgrastim. RESULTS: Median age at pegfilgrastim introduction was 19.1 years (range 3.9-52.3 years). In 14 cases pegfilgrastim replaced GCSF (filgrastim or lenograstim), after a median of 6.9 years of GCSF therapy. The dose of pegfilgrastim was usually one full vial per injection (except in five children, who received 1/6 to 1/2 a vial), resulting in a dose of between 50 and 286 microg/kg. The pegfilgrastim schedule ranged from two injections every 7 days to one injection every 30 days, with treatment-free periods. The median interval between the first and last dose of pegfilgrastim was 0.8 years (0.01-4.1 years). The absolute neutrophil count tended to increase more strongly on pegfilgrastim than on GCSF, but the difference was not statistically significant. During pegfilgrastim therapy, a severe infection occurred in two patients and recurrent ENT infections in two other patients. Bone pain was reported by nine patients, anemia and thrombocytopenia occurred in one patient (WHO grade III), chronic urticaria occurred in one patient (WHO grade III), and a single pegfilgrastim injection was followed by respiratory distress and death 15 days later in a patient with GDSIb. At the last update, 10 patients had stopped receiving pegfilgrastim and seven patients were still receiving pegfilgrastim. CONCLUSION: Compared to conventional GCSF, pegfilgrastim is more difficult to use in congenital neutropenia, with more frequent adverse events and sometimes poor efficacy.
Assuntos
Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Contagem de Células , Criança , Pré-Escolar , Avaliação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Pessoa de Meia-Idade , Neutropenia/complicações , Neutropenia/congênito , Neutropenia/epidemiologia , Neutrófilos , Dor , Polietilenoglicóis , Proteínas Recombinantes , Sistema de Registros , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Human herpesvirus 6 (HHV-6) isolates are classified into two variants, termed HHV-6A and HHV-6B, on the basis of distinct genetic, antigenic and biological characteristics, but the specific pathogenicity of each variant remains poorly understood. OBJECTIVES: To design a rapid, sensitive and specific real-time variant-specific PCR (VS-PCR) method to differentiate both variants in biological specimens. STUDY DESIGN: The VS-PCR was adapted from a real-time PCR assay, based on TaqMan technology, previously developed for the genome quantitation of both HHV-6 variants [Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, et al. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Meth 2002;100:27-35], a consensual reverse primer (Taq2) being changed into two variant-specific primers named H6A and H6B. This method was applied to a large set of biological specimens obtained in different pathological contexts. RESULTS: The sensitivity threshold was about 10 copies/well for HHV-6A-specific PCR (PCR-A) and 1 copy/well for HHV-6B-specific PCR (PCR-B). Both assays showed a linear dynamic range from 10 to 100,000 copies of HHV-6 DNA. Regarding the specificity and the capacity of discrimination of each assay, one variant could be detected and identified in the presence of more than 1000 times higher concentrations of the other variant in virus mixtures. The comparison of the results obtained with this VS-PCR with those previously obtained with a classic PCR method allowed us to validate our new technique on a wide panel of biological samples, including numerous patients with severe HHV-6-related symptoms. The high prevalence of HHV-6B was confirmed in healthy individuals and immunocompromised patients. HHV-6A was identified in distinct samples from several patients exhibiting neurological disorders. CONCLUSIONS: We developed a new VS-PCR assay, able to differentiate HHV-6A and HHV-6B in biological samples, even in the case of mixed infections. Our study confirms the wide prevalence of HHV-6B and highlights the potential greater neuropathogenic role of HHV-6A in immunocompromised patients and young infants.