Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Ann Hematol ; 98(8): 1973-1980, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111177

RESUMO

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea , Linfoma/diagnóstico , Linfoma/terapia , Mucosite/diagnóstico , Condicionamento Pré-Transplante/métodos , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , França , Humanos , Linfoma/classificação , Linfoma/mortalidade , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Mucosite/patologia , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo
3.
Bone Marrow Transplant ; 54(10): 1586-1594, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30770870

RESUMO

Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90.3% of the cohort. Median time to first infection was 13 days for bacterial, 32 days for viral and 20 days for fungal infections. Around 41% of these infections were of bacterial origin and 35% of viral origin, among which 48.8% of patients presented CMV reactivation. Median of GVHD relapse-free survival, progression-free survival and overall survival were 7.1 months, 19.9 months and 33.5 months, respectively. HSCT procedure was the primary or contributing cause of death (55.6%), followed by relapse of the original disease (34.2%). Infections accounted for 45.7% of the HSCT-related deaths. The present multicenter data on a large cohort of patients receiving HaploSCT with PTCy confirmed the feasibility of the procedure with an acceptable incidence of infectious complications, not different as compared to other haploidentical platforms or HLA-matched transplantation.

4.
J Viral Hepat ; 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30339311

RESUMO

Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long-term administration as monotherapies. The prevalence of resistance-associated substitutions (RASs) and fitness-associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment-naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full-length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment-naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next-generation sequencing at baseline who were treatment-eligible and treated with currently recommended drugs achieved a virological response. The presence of pre-existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.

5.
Ann Hematol ; 97(12): 2391-2401, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30091022

RESUMO

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7-73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3-60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2-46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate > 75% were associated with increased OS (p = 0.006 and p = 0.003, respectively) and PFS (p = 0.003 and p = 0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥ 8, were associated with decreased OS and PFS (p = 0.02 and p = 0.04, respectively). A high MSKCC score was associated with decreased OS (p = 0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p = 0.02 and p = 0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.


Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Metotrexato/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/imunologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
6.
Ann Hematol ; 97(9): 1601-1609, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29717367

RESUMO

The benefit of early admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) as soon as they develop organ injury is unknown. We performed a retrospective study on 92 patients admitted to the ICU to determine the impact of time from organ injury to ICU admission on outcome. The number of organ injuries prior to ICU admission was associated with an increased in-hospital mortality (OR 1.7, 95% CI 1-2.7, p = 0.04). Time between first organ injury and ICU admission was also associated with an increased in-hospital survival (OR 1.4, 95% CI 1.1-1.8, p = 0.02). A score combining these two covariates-the number of organ injuries/day (sum of days spent with each individual organ injury)-further improved the prediction of hospital survival. Patients with more organ injuries/day had significantly higher in-hospital mortality rate even after adjustment for refractory acute GVHD and the SOFA (OR 1.3, 95% CI 1-1.7, p = 0.02). Early ICU admission of allogeneic SCT recipients to the ICU as soon as they develop organ injury is associated with decreased in-hospital mortality.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospitalização/estatística & dados numéricos , Tempo para o Tratamento , Adulto , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade
7.
Bone Marrow Transplant ; 53(6): 749-755, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29523884

RESUMO

Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m2) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m2 melphalan is a beneficial procedure for MM patients with renal failure.

9.
Am J Hematol ; 93(3): 416-423, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29226497

RESUMO

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant.

10.
Am J Hematol ; 92(12): 1318-1323, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28960419

RESUMO

Patients with Acute Myelogenous Leukemia have a better outcome if reaching molecular remission. We compared the outcome of 373 patients autografted and 335 patients allografted with a 10/10 compatible unrelated donor in first molecular remission. Patients were stratified using the ELN European Leukemia Net classification. ELN favorable group: (234 auto and 70 unrelated transplants). By univariate analysis, in the auto group, the Non Relapse Mortality (NRM) was lower (3.7% versus 19%; P < 10-4 ), Relapse Incidence (RI) higher (29% versus 17%, P < 10-4 ), Leukemia Free Survival (LFS) identical (67% versus 64%) and Overall Survival (OS) better than in the allogeneic group (83% versus 62%; P = .008). By multivariate analysis, autologous transplantation was associated with a lower NRM (HR: 4, P = .01) and a better OS (HR: 2.08, P = .04). ELN intermediate group 1: (87 autologous and 172 unrelated transplants). By univariate analysis, in the auto group, NRM was lower (2.5% versus 11.8%; P = .03), RI higher (59% versus 18%, P < 10-6 ), LFS lower (39% versus 70%; P < 10-6 ) and OS lower than in the unrelated donor group (61% versus 74%; P = .005). By multivariate analysis, unrelated donor was superior to autologous transplantation for LFS (HR: 0.36, P < 10-5) and OS (HR: 0.53, P = .01). ELN intermediate group 2: (52 autologous and 93 unrelated donors). The outcome was identical. We conclude that good risk patients get higher benefit from autologous transplantation. Intermediate risk 2 patients have the same outcome and Intermediate risk 1 patients get higher benefit from unrelated donor transplants.


Assuntos
Leucemia Mieloide Aguda/terapia , Transplante Autólogo/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
11.
Blood ; 129(19): 2616-2623, 2017 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-28251914

RESUMO

High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV0) on rituximab PK and of TMTV0 and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV0 was measured by 18F-fluorodeoxyglucose-positron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m2 rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV0 and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV0 increased (R2 = 0.41, P < .0001). A high AUC in cycle 1 (≥9400 mg × h per liter) was associated with better response (odds ratio, 5.56; P = .0006) and longer PFS (hazard ratio [HR], 0.38; P = .011) and OS (HR, 0.17; P = .001). A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV0 was constructed, and the 375 mg/m2 classical dose would be suitable for patients with TMTV0 <281 cm3 In summary, rituximab exposure is influenced by TMTV0 and correlates with response and outcome of DLBCL patients. Dose individualization according to TMTV0 should be evaluated in prospective studies. These studies were registered at www.clinicaltrials.gov as #NCT00498043 and #NCT00841945.


Assuntos
Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Rituximab/administração & dosagem , Rituximab/metabolismo , Rituximab/farmacocinética , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Adulto Jovem
12.
Clin Pharmacokinet ; 56(6): 635-647, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27783363

RESUMO

BACKGROUND AND OBJECTIVES: Rituximab is an anti-CD20 monoclonal antibody approved in the first-line treatment of patients with chronic lymphocytic leukemia (CLL). Rituximab pharmacokinetics shows a time dependency possibly related to changes in the target antigen amount over time. The purpose of this study was to quantify the influence of both CD20 antigenic mass and the FcγRIIIA genetic polymorphism on rituximab pharmacokinetics in CLL. METHODS: Rituximab pharmacokinetics was described in 118 CLL patients using a semi-mechanistic model including a latent target antigen turnover, which allowed the estimation of rituximab target-mediated elimination in addition to the endogenous clearance. RESULTS: Target-mediated elimination rate constant increased with the baseline CD20 count on circulating B cells (p = 0.00046) and in patients with the FCGR3A-158VV genotype (p = 0.0016). Physiologic elimination of antigen was lower in the Binet C disease stage (p = 0.00018). The effects of these covariates on rituximab concentrations were mainly visible at the beginning of treatment. Body surface area also increased central and peripheral volumes of distribution (p = 1.3 × 10-5 and 0.0015, respectively). CONCLUSIONS: A pharmacokinetic model including target-mediated elimination accurately described rituximab concentrations in CLL and showed that rituximab 'consumption' (target-mediated elimination) increases with increasing baseline antigen count on circulating B cells and in FCGR3A-158VV patients. CLINICAL TRIAL REGISTRATION: NCT01370772.


Assuntos
Antígenos CD20/metabolismo , Antineoplásicos/farmacocinética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Modelos Biológicos , Receptores de IgG/genética , Rituximab/farmacocinética , Antineoplásicos/sangue , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linfócitos B/metabolismo , Superfície Corporal , Feminino , Genótipo , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Rituximab/sangue , Rituximab/farmacologia , Rituximab/uso terapêutico
13.
Clin Genitourin Cancer ; 15(1): 163-167, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27444987

RESUMO

BACKGROUND: The optimal management of advanced seminoma that relapses after chemotherapy remains unknown. We retrospectively analyzed outcomes with the use of high-dose chemotherapy (HDCT). PATIENTS AND METHODS: Eligibility included adult male patients with pure seminomatous histology and treatment with salvage HDCT. Data of patients who received HDCT from 13 European Society for Blood and Marrow Transplantation (EBMT) centers were used. Multivariable Cox analyses evaluated the association of prespecified factors (line of treatment, prior radiotherapy, and chemosensitivity according to standard definition), with progression-free (PFS) and overall survival (OS). The prognostic ability of the model was assessed through the concordance statistic. RESULTS: From December 2002 to December 2012, 46 cases were identified. Median age was 38 years (interquartile range, 35-46 years). HDCT was provided as second-line therapy (n = 14, 30.4%) and in third-line or beyond third-line therapy (n = 20, 43.5%; 12 had missing information). Sixteen patients (34.8%) received paraortic and/or iliac radiotherapy, and 10 (21.7%) had disease that was cisplatin refractory or absolutely refractory. Median follow-up was 22 months (interquartile range, 8-56). On multivariable Cox analysis, refractory disease was a significantly negative prognostic factor for both PFS (hazard ratio, 6.04; 95% confidence interval, 1.86-19.64) and OS (hazard ratio, 3.93; 95% confidence interval, 1.07-14.45), while prior radiotherapy trended to significance for both. The c index was 0.74 and 0.66 for PFS and OS, respectively. The small numbers and the lack of any comparison with conventional-dose chemotherapy are major study limitations. CONCLUSION: Despite our small sample size, this retrospective analysis suggested that HDCT may represent a valuable therapeutic option for patients with a pure seminoma after standard-dose chemotherapy failure. Our observation requires validation through a prospective study.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Terapia de Salvação/métodos , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Intervalo Livre de Doença , Etoposídeo/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Transplantation ; 101(2): 437-444, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26950729

RESUMO

BACKGROUND: Admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) remains controversial, especially when graft-versus-host disease (GVHD) is present. METHODS: We performed a retrospective study to assess prognostic factors of survival in all allogeneic SCT recipients admitted to the ICU between 2002 and 2013 in our center which has flexible admission criteria, especially regarding GVHD. RESULTS: Of 349 patients who underwent allogeneic SCT during the study period, 92 patients (26%) were admitted to the ICU. Intensive care unit and hospital discharge rates were 66% and 46%, respectively, whereas 1 year survival was 24%. Acute GVHD, either grade III to IV (30 patients, 33%) or refractory (12 patients, 13%) had a nonsignificant impact on hospital mortality (odds ratio [OR], 2.1; P = 0.1; OR, 5, P = 0.05, respectively). Fifty percent of patients required invasive mechanical ventilation, 30% required vasopressors, 17% required renal replacement therapy, and 28% had liver impairment (bilirubin >34 µmol/L), each of these parameters defining organ failure. Mortality was closely associated with the number of organ failures as hospital discharge rates were 69%, 50%, 42%, and 0% among patients with 0 (26 patients), 1 (26 patients), 2 (26 patients), and 3 to 4 (14 patients) organ failures, respectively (OR, 2.7; 95% confidence interval, 1.6-4.6; P < 0.001 according to the number of organ failures). CONCLUSIONS: Early mortality of allogeneic SCT recipients admitted to the ICU is especially influenced by the number of organ failures and therefore patients with 0 to 2 organ failures should be considered if required. Refractory GVHD affects survival but not within the confined ICU admission.


Assuntos
Cuidados Críticos , Doença Enxerto-Hospedeiro/terapia , Insuficiência de Múltiplos Órgãos/terapia , Transplante de Células-Tronco/efeitos adversos , Adulto , Distribuição de Qui-Quadrado , Feminino , França , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Análise Multivariada , Razão de Chances , Admissão do Paciente , Alta do Paciente , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento
17.
J Clin Microbiol ; 49(3): 1154-6, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21177906

RESUMO

The new version of the INNO-LiPA HBV genotyping assay (Innogenetics) developed to identify all hepatitis B virus (HBV) genotypes, A to H, has been evaluated in comparison with sequencing of PCR-amplified HBV DNA from 200 samples before or after cloning. The genotyping data obtained with INNO-LiPA were in agreement with those from direct sequencing in the 179 samples characterized by the two methods. INNO-LiPA revealed 28 mixed infections. However, sequencing after molecular cloning confirmed only 15 of them and did not identify any that were of genotype H (n = 9). Our study demonstrates that INNO-LiPA overestimates mixed infections as a result of erroneous genotype H detection.


Assuntos
Técnicas de Laboratório Clínico/métodos , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite B/virologia , Técnicas de Diagnóstico Molecular/métodos , Virologia/métodos , Erros de Diagnóstico , Genótipo , Vírus da Hepatite B/isolamento & purificação , Humanos , Incidência
18.
Transfusion ; 50(12): 2607-18, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20553432

RESUMO

BACKGROUND: Hepatitis B virus (HBV) diversity is characterized by eight genotypes correlated to eight hepatitis B surface antigen (HBsAg) subtypes, which differ in their geographical distribution. STUDY DESIGN AND METHODS: To establish virologic characteristics and the evolution of HBV diversity, we carried out a study over a 9-year period in HBV-infected French blood donors. HBsAg subtyping based on specific antibody method concerned 2901 donors, from whom 940 have been analyzed by an S-gene sequencing to determine genotypes and S-gene mutations. RESULTS: HBsAg subtypes were distributed as follows: ayw2, 34.4%; adw2, 25.7%; ayw1, 10.2%; ayw4, 14.9%; adr, 7.8%; ayw3, 6.4%; and adw4, 0.7%. Ayw4 (Genotype E) proportion increased over time in correlation with an increased proportion of subjects originated from sub-Saharan Africa. The genotype observed with the highest proportion was D (43.0%), then A (26.2%), E (17.5%), B (6.5%), C (6.4%), and F (0.4%). Genotype B had the highest proportion of hepatitis B e antigen (39.2%) and the highest viral loads (VLs). Forty-three (5.5%) isolates presented one (n=35) or multiple (n=8) amino acid envelope substitutions. Donors infected with mutated isolates had lowest VLs. rtA181T/sW172 stop mutation associated with resistance to nucleos(t)ide analogs was detected in two donors suggesting a transmission of these isolates. CONCLUSION: This extensive study shows that HBV genotype evolution is closely linked to the geographical origin of subjects and that the occurrence of viral envelope mutants is not an exceptional event in healthy HBV chronic carriers. Blood donors rarely recruited in HBV studies provide further relevant information on the characteristics of HBV diversity.


Assuntos
Infecções Assintomáticas , Doadores de Sangue , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Polimorfismo Genético , Adulto , Infecções Assintomáticas/epidemiologia , Coleta de Dados , Evolução Molecular , Feminino , França/epidemiologia , Frequência do Gene , Genótipo , Geografia , Hepatite B/sangue , Hepatite B/virologia , Humanos , Masculino , Estudos Soroepidemiológicos , Sorotipagem , Fatores de Tempo
20.
Transfusion ; 46(12): 2047-52, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17176315

RESUMO

BACKGROUND: The objective was to evaluate the performance of nucleic acid testing (NAT) in the detection of hepatitis B virus (HBV) infection in hepatitis B surface antigen (HBsAg)-positive blood donations. STUDY DESIGN AND METHODS: A total of 253 HBsAg- and anti-hepatitis B core antigen (HBc)-positive samples (50 hepatitis B e antigen [HBeAg]-positive and 203 anti-HBe-positive) from blood donations collected in France were studied. The samples were investigated with a blood screening assay (Procleix Ultrio, Chiron/Gen-Probe) in minipool (MP; x8) and in individual-donation (ID) testing. All nonreactive samples were retested once, and nonreactive MP samples were assayed for viral load (VL). RESULTS: All 50 HBeAg-positive samples were reactive in MP-NAT and ID-NAT. Of the 203 anti-HBe-positive donations, 80.3 percent were MP- and ID-reactive, 17.2 percent were MP-nonreactive and ID-reactive, and 2.5 percent were nonreactive in ID-NAT. Overall the sensitivity of ID-NAT was 98 percent versus 84 percent for MP-NAT. After retesting, 16 of the 35 MP-nonreactive and/or ID-reactive donations became MP-reactive and 2 of the ID-nonreactive donations became NAT-reactive. The capacity of Procleix Ultrio to detect HBV DNA was not related to HBsAg subtype, but correlated with the VL: the mean VL in the group of MP-nonreactive samples was 1,420 copies per mL vs. 17,000 copies per mL in the group of 40 MP-reactive samples. CONCLUSION: These results demonstrate that HBV-NAT in ID format is far more effective in detecting viremia in chronic HBsAg carriers than in MP-NAT. The sensitivity of the NAT assay needs to be improved to be considered for replacing the current HBsAg assays, especially when anti-HBc testing is not performed.


Assuntos
Doadores de Sangue , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Humanos , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA