Assuntos
Linfoma de Burkitt , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , Humanos , Adulto , Receptores de Antígenos Quiméricos/genética , Quimioterapia de Consolidação , Antígenos CD19 , Imunoterapia Adotiva/efeitos adversos , Lectina 2 Semelhante a Ig de Ligação ao Ácido SiálicoRESUMO
The treatment of B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement poses a significant clinical challenge because most chemotherapeutic agents exhibit weak permeability to the blood-brain barrier (BBB). In addition, current anti-CNS leukemia treatments often bring short or long-term complications. Immunotherapy including chimeric antigen T-cell therapy and bispecific antibody have shown profound treatment responses in relapsed/refractory B-ALL. However, there is a lack of data on the efficacy of bispecific antibody in treating B-ALL with CNS involvement. Here, we report two ALL patients with CNS leukemia who received blinatumomab. Case 1 was diagnosed with chronic myeloid leukemia in lymphoid blast phase. The patient developed CNS leukemia and bone marrow relapse during the treatment with dasatinib. Case 2 was diagnosed with B-ALL and suffered early hematologic relapse and cerebral parenchyma involvement. After treatment with one cycle of blinatumomab, both patients achieved complete remission in the bone marrow and CNS. Furthermore, this is the first report on the efficacy of blinatumomab in treating CNS leukemia with both of the cerebral spinal fluid and the cerebral parenchymal involvement. Our results suggest that blinatumomab might be a potential option for the treatment of CNS leukemia.
Assuntos
Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recidiva , Sistema Nervoso CentralRESUMO
We conducted a single-arm, open-label, single-center phase 1 study to assess the safety and efficacy of multicycle-sequential anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and tyrosine kinase inhibitor (TKI) as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-cell acute lymphoblastic leukemia. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another 3 cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at 3 different doses. The phase 1 results of the first 15 patients, including 2 withdrawals, are presented. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There was no incidence of cytokine release syndrome above grade 2 or immune effector cell-associated neurotoxicity syndrome or grade 4 nonhematological toxicities. All 13 patients achieved complete remission, including 12 patients with a complete molecular response (CMR) at the data cutoff. The relapse-free survival was 84%, and the overall survival was 83% with a median follow-up of 27 months. The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings could form the basis for the development of an allo-HSCT-free consolidation paradigm. This trial was registered at www.clinicaltrials.gov as #NCT03984968.
Assuntos
Antígenos CD19 , Imunoterapia Adotiva , Linfoma de Células B , Síndromes Neurotóxicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Humanos , Antígenos CD19/imunologia , Antígenos CD19/uso terapêutico , Quimioterapia de Consolidação , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T , Imunoterapia Adotiva/métodosRESUMO
CD19 chimeric antigen receptor-T (CAR-T) cell therapy has achieved remarkable results in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the cytokine release syndrome (CRS) was presented in most patients as common toxicity and severe CRS (sCRS) characterized by the sharp increase in interleukin-6 (IL-6) could be life-threatening. We conducted a phase II clinical trial of ssCAR-T-19 cells, anti-CD19 CAR-T cells with shRNA targeting IL-6, in 61 patients with r/r B-ALL. This trial was registered at www.clinicaltrials.gov as #NCT03275493. Fifty-two patients achieved CR while nine patients were considered NR. The median duration of response (DOR) and overall survival (OS) were not reached (>50 months). CRS developed in 81.97% of patients, including 54.10% with grades 1 to 2 (grade 1, 31.15%; grade 2, 22.95%) and 27.87% with grades 3 to 4 (grade 3, 26.23%; grade 4, 1.64%). sCRS occurs earlier than mild CRS (mCRS). A multivariable analysis of baseline characteristics identified high bone marrow disease burden and poor genetic risk before infusion as independent risk factors for sCRS. After infusion, patients with sCRS exhibited larger expansion of ssCAR-T-19 cells, higher peak levels of IL-6, IL-10, and IFN-γ, and suffered more severe hematological and non-hematological toxicities compared with those with mCRS.
Assuntos
Linfoma Folicular , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos , Síndrome da Liberação de Citocina/etiologia , Humanos , Interleucina-6/genética , Linfoma Folicular/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico , Fatores de RiscoRESUMO
Synthetic pigments are still used instead of natural pigments in many foods and their residues in food could be an important risk to human health. A simple and rapid analytical method combining the low-cost extraction protocol with ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) was developed for the simultaneous determination of seven synthetic pigments used in colored Chinese steamed buns. For the first time, ethanol/ammonia solution/water (7:2:1, v/v/v) was used as extraction solution for the synthetic pigments in colored Chinese steamed buns. The results showed that the property of the extraction solution used in this method was more effective than critic acid solution, which is used in the polyamide adsorption method. The limits of quantification for the seven synthetic pigments ranged from 0.15 to 0.50 µg/kg. The present method was successfully applied to samples of colored Chinese steamed buns for food-safety risk monitoring in Zhejiang Province, China. The results found sunset yellow pigment in six out of 300 colored Chinese steamed buns (from 0.50 to 32.6 µg/kg).
Assuntos
Corantes/análise , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Adsorção , Amônia/química , Calibragem , Cromatografia , Cromatografia Líquida , Etanol/química , Alimentos , Nylons/química , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Água/químicaRESUMO
In this study, a rapid and accurate ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) method coupled with the isotope internal standard dilution technique was established and validated to determine trace dicyandiamide (DCD) in mussels. The sample was extracted by acetonitrile, and chromatographic separations were performed on an Acquity UPLC BEH Amide column by using water-acetonitrile (9:91, v/v) as the mobile phase within 3 min. DCD was determined by using DCD-(15)N4 as an internal standard. The results showed that the recoveries were between 96.2 and 103 % with relative standard deviations (RSDs) in the range of 0.6-6.0 %. The limit of quantification (LOQ) was 0.05 µg/kg. This method can be applied to the routine analysis for the rapid and sensitive determination of trace DCD in mussels. Overall, the data reiterate the importance of investigating the presence of DCD in marine biological samples, which can act as food quality controls for human health.
Assuntos
Bivalves/química , Cromatografia Líquida de Alta Pressão/métodos , Guanidinas/análise , Espectrometria de Massas em Tandem/métodos , Poluentes Químicos da Água/análise , Animais , China , Análise de Alimentos/métodos , Humanos , Técnicas de Diluição do Indicador , Isótopos , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
Outbreaks of classical swine fever (CSF) have caused serious economic consequences in China. Phylogenetic analysis based on full-length E2 gene sequences showed that five classical swine fever virus (CSFV) isolates collected from Hunan province in 2011 and 2012, together with seven other isolates from neighboring provinces, Guangdong (5) and Guangxi (2), could be classified as a new subgenotype 2.1c, which may have been endemic in the south of China for at least fourteen years. Subgenotype 2.1c isolates share 90.2-94.9% and 89.9-93.8% nucleotide sequence similarity separately with those of subgenotype 2.1a and 2.1b in E2 gene, which are lower than the nucleotide identities between subgenotype 2.1a and 2.1b (91.1-95.7%). Further analysis based on a partial E2 gene sequence (216 nt) indicated that subgenotype 2.1c isolates are also circulating in Thailand. Alignment of E2 amino acid sequences showed that subgenotype 2.1c isolates exhibit a SPA â TPV substitution at positions 777 and 779 compared with subgenotypes 2.1a and 2.1b.
Assuntos
Vírus da Febre Suína Clássica/classificação , Vírus da Febre Suína Clássica/genética , Genótipo , Filogenia , Proteínas do Envelope Viral/genética , Sequência de Aminoácidos , Animais , China/epidemiologia , Peste Suína Clássica/epidemiologia , Peste Suína Clássica/virologia , Vírus da Febre Suína Clássica/isolamento & purificação , Dados de Sequência Molecular , Alinhamento de Sequência , Suínos , Proteínas do Envelope Viral/químicaRESUMO
Two isolates of a new classical swine fever virus (CSFV) subgenotype, 2.1c (HNLY-2011 and HNSD-2012), were recently isolated from pigs in Hunan Province, China. The most significant difference in the amino acid sequences of the polyproteins from subgenotypes 2.1a and 2.1b is an SPA â TPV amino acid substitution at positions 777 and 779 in the E2 protein.
RESUMO
OBJECTIVE: To explore the willingness of care and related influencing factors among caregivers of those 'left at hometown' children under 7 years in Chinese rural areas. METHODS: Questionnaires were used to survey caregivers (n = 7585) who were identified by multi-stage stratified cluster sampling. Multi-factor ordinal logistic regression analysis was used to screen the influencing factors on the willingness of care among them. RESULTS: The percentage on 'very willing', 'willing', 'unwilling' on those 'left at home' children were 41.1%, 55.4% and 3.5% respectively in the group with single parent while 19.5%, 71.4% and 9.1% respectively in the group of both parents having left home. Data from the multi-factor ordinal logistic regression analysis showed that factors including the age of the caregiver, annual per capita income for caregivers' families, social connections and the length of children's mother being absent, amount of fees for living provided by parent/parents, and the child's age and lifestyle, being the only child or not, and the age of the child when the parent/parents left the residence etc, were related to the willingness of care of the givers. CONCLUSION: Willingness of care calls for attention and urgent improvement. Influencing factors and measures need to be taken when necessary.
Assuntos
Cuidadores , Educação Infantil/psicologia , Proteção da Criança , Adulto , Idoso , Pré-Escolar , China , Família , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , População Rural , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To understand emotional, behavioral problems and related determinants among rural stranded children and to provide evidence for further psychological support. METHODS: A total of 3944 caregivers of children in the rural areas and aged 4 to 7 years but without parents around, were randomly selected. Data were collected through Strengths and Difficulties Questionnaires (the edition for parents, SDQ). RESULTS: The overall prevalence of children with behavioral/emotional problems was 43.6% among those stranded children including 8.3% having experienced emotional symptoms, 9.5% reported to be displaying 'conduct' problems, 8.7% exhibited significant hyperactivity/inattention, 18.9% experienced peer relationship problems and 16.8% having prosocial behaviors. The prevalence of behavioral/emotional problems was significantly higher in boys than those in girls and in lower age groups. Significant differences were also found in conduct problems, hyperactivity/inattention and prosocial behaviors (P<0.01). The result from logistic regression analysis showed that factors as education level and motivation of the caregivers as well as financial support from the parents were related to emotional/ behavioral problems among the stranded children. CONCLUSION: The prevalence of emotional and behavioral problems was high among children living the rural areas but without their parents around which should call for psychological intervention.