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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 327-333, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35395958

RESUMO

OBJECTIVE: To establish an immune gene prognostic model of acute myeloid leukemia (AML) and explore its correlation with immune cells in bone marrow microenvironment. METHODS: Gene expression profile and clinical data of TCGA-AML were downloaded from TCGA database. Immune genes were screened by LASSO analysis to construct prognosis prediction model, and prediction accuracy of the model was quantified by receiver operating characteristic curve and area under the curve. Survival analysis was performed by Log-rank test. Enriched pathways in the different immune risk subtypes were evaluated from train cohort. The relationship between immune prediction model and bone marrow immune microenvironment was verified by flow cytometry in the real world. RESULTS: Patients with low-risk score of immune gene model had better prognosis than those with high-risk score. Multivariate analysis showed that the immune gene risk model was an independent prognostic factor. The risk ratio for AML patients in the training concentration was HR=24.594 (95%CI: 6.180-97.878), and the AUC for 1-year, 3-year, and 5-year overall survival rate was 0.811, 0.815, and 0.837, respectively. In addition, enrichment analysis of differential gene sets indicated activation of immune-related pathways such as cytokines and chemokines as well as autoimmune disease-related pathways. At the same time, real world data showed that patients with high immune risk had lower numbers of CD8+T cells and B lymphocytes compared with low immune risk patients. CONCLUSION: We constructed a stable prognostic model for AML, which can not only predict the prognosis of AML, but also reveal the dysregulation of immune microenvironment.


Assuntos
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Prognóstico , Curva ROC , Fatores de Risco , Transcriptoma , Microambiente Tumoral/genética
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 685-689, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105457

RESUMO

OBJECTIVE: To investigate the effect of V-9302 (an antagonist of transmembrane glutamine flux) on the proliferation and apoptosis of acute myeloid leukemia cells HL-60 and KG-1. METHODS: HL-60 and KG-1 cells at logarithmic phase were treated by different concentrations of V-9302. CCK-8 assay was used to detect the proliferation of the cells. Annexin V-FITC / PI double staining flow cytometry was used to detect the apoptosis of HL-60 and KG-1 cells. The expressions of BAX, BCL-2 and Caspase3 were detected by RT-qPCR and Western blot. RESULTS: V-9302 could significantly inhibit the growth of HL-60 and KG-1 cells. The concentration of V-9302 at 10, 20 µmol/L could significantly promote the apoptosis of HL-60 and KG-1 cells(P<0.05). The results of apoptosis related gene detection showed that when V-9302 was applied to HL-60 and KG-1 cell lines at 10 and 20 µmol/L, the expression levels of Pro-apoptotic protein genes BAX and Caspase3 in HL-60 and KG-1 were significantly higher than those in control group (P<0.05), while the expression level of anti-apoptotic protein gene BCL-2 was significantly lower than that in the control group (P<0.05). The results of Western blot were basically consistent with that of RT-qPCR. CONCLUSION: Competitive antagonist of transmembrane glutamine flux V-9302 can significantly promote the apoptosis of acute myeloid leukemia cell lines HL-60 and KG-1.


Assuntos
Glutamina , Leucemia Mieloide Aguda , Apoptose , Proliferação de Células , Células HL-60 , Humanos
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 944-950, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105498

RESUMO

OBJECTIVE: To investigate the clinical characteristics and risk factors of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). METHODS: Clinical data from 270 SAA patients with allo-HSCT were retrospectively analyzed, including 108 sib congruence patients and 162 substitute donors (68 unrelated donor congruence patients and 94 related haploid patients). Different pretreatment schemes were selected for different transplantation modes. The HLA-identical sibling and haploid grafts were all bone marrow and peripheral blood stem cells, and the grafts from unrelated donors were peripheral blood stem cells. After granulocyte implantation, blood CMV-DNA was regularly monitored. Flow cytometry was also used to determine the absolute number of CD3+, CD4+T lymphocytes and CD19+B lymphocytes at 1, 2, 3, 6 and 12 months after transplantation. RESULTS: CMV infection occurred in 229 of 270 patients with an incidence of 84.8%. Among them, 18 patients developed giant cell disease. Univariate analysis showed that alternative donors (unrelated total and haploid donors), mycophenolate mofetil and acute graft-versus-host disease were statistically significantly associated with CMV infection (P<0.05). Multivariate analysis showed that alternative donors were associated with CMV infection. The recovery of CD3+ and CD4+ in 6 months in the substitute donors was delayed in comparison with that in the full sib group. CONCLUSION: After allo-HSCT, substitute donors are more easily to develop CMV infection than full-sibling donors, and the reconstruction of immune function is delayed after transplantation.


Assuntos
Anemia Aplástica , Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos
4.
Ann Hematol ; 100(9): 2363-2373, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33988738

RESUMO

With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6-8/8 HLA-matched unrelated donor (MUD) or 6-7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6-7/8 MRD, and 42 (36.5%) from a 6-7/8 MUD. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was higher in the 6-7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6-7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6-7/8 MUD, 6-7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6-7/8 MRD or 6-7/8 MUD is comparable to that from an 8/8 MUD.


Assuntos
Anemia Aplástica/terapia , Bussulfano/uso terapêutico , Antígenos HLA/análise , Imunossupressores/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Histocompatibilidade , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
5.
Platelets ; 32(5): 633-641, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32614630

RESUMO

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.


Assuntos
Hemorragias Intracranianas/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Feminino , Humanos , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Resultado do Tratamento
6.
Clin Cancer Res ; 27(1): 255-266, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262139

RESUMO

PURPOSE: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. EXPERIMENTAL DESIGN: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. RESULTS: Six flow cytometry-validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. CONCLUSIONS: Our immune risk score complements current AML prediction models.


Assuntos
Leucemia Mieloide Aguda/mortalidade , Microambiente Tumoral/imunologia , Conjuntos de Dados como Assunto , Feminino , Citometria de Fluxo , Regulação Leucêmica da Expressão Gênica/imunologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , RNA-Seq , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Taxa de Sobrevida , Linfócitos T/imunologia , Microambiente Tumoral/genética
7.
Front Genet ; 12: 790990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35058969

RESUMO

Severe aplastic anemia (SAA) is an autoimmune disease characterized by immune-mediated destruction of hematopoietic stem and progenitor cells. Autoreactive CD8+ T cells have been reported as the effector cells; however, the mechanisms regulating their cell activation in SAA remain largely unknown. Here, we performed proteomics and metabolomics analyses of plasma and bone marrow supernatant, together with transcriptional analysis of CD8+ T cells from SAA patients and healthy donors, to find key pathways that are involved in pathogenic CD8+ T-cell activation. We identified 21 differential proteins and 50 differential metabolites in SAA patients that were mainly involved in energy metabolism, complement and coagulation cascades, and HIF-1α signaling pathways. Interestingly, we found that these pathways are also enriched in T cells from SAA patients by analyzing available single-cell RNA sequencing data. Moreover, CD8+ T cells from SAA patients contain a highly activated CD38+ subset, which was increased in the bone marrow of SAA patients and a murine model of SAA. This subset presented enriched genes associated with the glycolysis or gluconeogenesis pathway, HIF-1α signaling pathway, and complement associated pathways, all of which were of importance in T-cell activation. In conclusion, our study reveals new pathways that may regulate CD8+ T-cell activation in SAA patients and provides potential therapeutic targets for SAA treatment.

8.
J Clin Oncol ; 38(29): 3367-3376, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650683

RESUMO

PURPOSE: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial. PATIENTS AND METHODS: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. RESULTS: From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] v 52.5% [95% CI, 52.1% to 52.9%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] v 23.2% [95% CI, 22.9% to 23.5%]; P = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; P = .003). CONCLUSION: Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.


Assuntos
Soro Antilinfocitário/administração & dosagem , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Ciclosporina/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Irmãos , Doadores de Tecidos
9.
Sci China Life Sci ; 63(10): 1552-1564, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32086670

RESUMO

Prophylactic/preemptive donor lymphocyte infusion (p/pDLI) and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia (RRAL), but real-world data remain scarce. We conducted a multicenter, population-based analysis of 932 consecutive patients. The three-year leukemia-free survival (LFS) rates were 56% for patients receiving both p/pDLI and intensified myeloablative conditioning (MAC) (intenseMAC) and 30% for those who received neither therapy per landmark analysis. Multivariable analyses were run separately for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality. IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL, while there was no impact of intenseMAC observed in AML. p/pDLI achieved superior outcomes in both matched-sibling donor (MSD) and haploidentical donor transplantation, while intenseMAC only influenced MSD outcomes. Data suggest that RRAL patients receiving "total therapy" by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS, with p/pDLI being safer with a more extensive impact relative to intenseMAC. Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.


Assuntos
Imunoterapia Adotiva/métodos , Leucemia/terapia , Transfusão de Linfócitos , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Leucemia/imunologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Prevenção Secundária , Doadores de Tecidos , Transplante Haploidêntico , Transplante Homólogo , Adulto Jovem
10.
Clin Transplant ; 34(3): e13810, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011059

RESUMO

This retrospective multicenter cohort study aimed to compare the outcome of haploidentical hematopoietic stem cell transplantation (HID-HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anemia (SAA) patients 40 years of age and older. With a median follow-up time of 17.6 months, 85 consecutive patients were enrolled in the study, and the median patient age was 45 years (40, 58). The cumulative engraftment rates of neutrophil and platelet were 98.8 ± 0.0% and 92.9 ± 0.1%. The cumulative incidences of Grade 2-4 acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) at 3 years were 14.1 ± 0.1% and 17.3 ± 0.2%. The 3-year estimated overall survival (OS) and failure-free survival (FFS) were 91.2 ± 3.2% and 89.7 ± 3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG score ≥2. HID-HSCT was associated with a higher incidence of GvHD, but the difference of 3-year estimated OS between HID group and the other two cohorts was not significant (86.7 ± 6.4% for HID vs 92.1% ± 4.4% for MSD and 100% for URD, P = .481). HID-HSCT might be a feasible alternative option for selected SAA patients aged 40 years and older without a matched donor.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Anemia Aplástica/terapia , Estudos de Coortes , Doença Enxerto-Hospedeiro/etiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento , Doadores não Relacionados
11.
J Cancer ; 10(19): 4707-4718, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528236

RESUMO

Background: Long non-coding RNAs (lncRNAs), which are over 200 nt in length, have a key role in tumorigenesis and disease progression. To explore the role of prognostic lncRNAs in adult acute myeloid leukemia (AML), the expression profiles of lncRNAs and mRNAs in AML were analyzed. Methods: The RNAseq data of 167 adult AML patients and the corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA), which is a publicly available database. The RPKM values of the RNAseq data were subjected to weighted gene co-expression network analysis (WGCNA) in modularization. Results: We identified survival specific lncRNAs and mRNAs, which were divided into modules by coexpression analysis. The lncRNAs were mainly annotated into "Fc gamma R-mediated phagocytosis". The hub lncRNA and co-expressed mRNAs were further selected for analysis of risk stratification. LncRNA-LOC646762 may contribute to AML through the "endocytosis" signaling pathway. Finally, the expression levels of LOC646762 and co-expressed CCND3, CBR1, C10orf54, CD97 and BLOC1S1 in the adult AML patients and healthy volunteers were validated by qRT-PCR, and then their roles in prognosis and risk stratification were identified. Conclusions: Prognostic lncRNA-LOC646762, which may contribute to AML through the "endocytosis" signaling pathway, may act as a biomarker for predicting the survival of adult AML patients, as well as for risk stratification.

12.
J Hematol Oncol ; 12(1): 87, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477147

RESUMO

BACKGROUND: Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. METHODS: We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. RESULTS: Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0-1), or moderate graft mononuclear cell (MNC) counts (6-10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0-1). CONCLUSIONS: Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.


Assuntos
Anemia Aplástica/terapia , Doadores de Tecidos/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Transplante Haploidêntico , Adulto Jovem
13.
Acta Haematol ; 142(3): 162-170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091521

RESUMO

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.


Assuntos
Anemia Aplástica , Soro Antilinfocitário/administração & dosagem , Ciclosporina/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Medicina Tradicional Chinesa , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Criança , Pré-Escolar , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 239-245, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738477

RESUMO

OBJECTIVE: To investigate the change of microbial diversity and its relation with gastrointestinal (GI) graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Fecal samples were collected at the time point of 2 weeks before transplantation (pre-transplant group), 1 month after transplantation (post-tranplant group) and onset of GI GVHD in 65 hematonosis patients, which were also collected in 26 donors and 10 healthy subjects (control group). 16S rRNA was extracted from fecal microbiotas whose V4 variable region was amplified. The amplification products were sequenced in Illumina HiSeq 2500 platform, and the sequencing results were analyzed and compared. RESULTS: The microbial diversity was 5.70(3.74, 10.60)in pre-transplant group, 7.30(4.89, 11.41)in control group, and the differences between them were not statistically significant. The microbial diversity was 3.88(2.39, 6.49)in post-transplant group, lower than that in control group and pre-transplant group. After transplantation, the microbial diversity was 4.24(2.47, 7.16)in the patients without GI GVHD, while the microbial diverosity was 2.90 (1.48, 5.64) in patients subsequently suffered from GI GVHD, but the differences between them were not statistically significant. The microbial diversity was 2.13(1.76, 3.75)onset of GI GVHD, which was lower than that without GI GVHD. CONCLUSION: Intestinal microbial diversity decreases after allo-HSCT, and is associated with with Gl GVHD.


Assuntos
Trato Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , RNA Ribossômico 16S
15.
Bone Marrow Transplant ; 54(8): 1319-1326, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30670825

RESUMO

Our study aimed to compare treatment outcomes between hematopoietic stem cell transplantation (HSCT) from haploidentical donors (HID) and immunosuppressive therapy (IST) in adults with acquired severe aplastic anemia (SAA). The medical records of 113 SAA adults who received IST, including rabbit ATG and cyclosporin (N = 37), or HID HSCT (N = 76) within 6 months of diagnosis at two institutions were retrospectively reviewed. Estimated 8-year overall survival (OS) was comparable between the IST and HID HSCT groups (75.6 vs. 83.7%, respectively, P = 0.328), but failure free survival (FFS) was significantly lower in IST group than HID HSCT group (38.5 vs. 83.7%, respectively, P = 0.001). Furthermore, a significant improvement in FFS was observed with HSCT over IST in patients under 40 years old. At the last follow-up, patients in HSCT group achieved better Karnofsky Performance Status (KPS) than those in IST group (100 [20-100] vs. 90 [20-100], P = 0.002). In terms of blood count, 83.1% (54/65) of patients in HSCT group showed complete recovery compared to only 38.2% (13/34) in IST group (P < 0.001). These data suggest that HID HSCT could be an effective alternative treatment option for SAA adults, and additional prospective studies are necessary.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Anemia Aplástica/mortalidade , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(6): 1761-1767, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29262912

RESUMO

OBJECTIVE: To explore the value of CD3+CD4+ T cell count in prediction of viral infections after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in the patients with severe aplastic anemia(SAA). METHODS: A total of 78 SAA patients with allo-HSCT in Guangzhou First People's Hospital from January 2014 to July 2016 were enrolled in this study. The absolute numbers of CD3+CD4+T cells were measured by flow cytometry at 1,2,3,6, and 12 month after allo-HSCT. According to the cell counts, the patients were divided into 3 groups: i.e. <50/µl (n=120), 50-100/µl(n=48) and >100/µl(n=123)groups. The infection incidences of human cytomegalovirus (HCMV) and Epstein-Barr virus(EBV) within 2 weeks around each time point were compared between different groups. According the counts of CD3+CD4+T cells at 3 months after-transplant, these patients were divided into 2 groups, i.e.>100/µl (n=30) and ≤100/µl (n=48). The incidences and duration of HCMV and EBV infection, overall survival rate were compared between 2 groups. RESULTS: The incidences of CMV and EBV infection significantly decreased in CD3+CD4+ T cell >100/µl group as compared with <50/µl and 50-100/µl groups. At 3 months after-transplant, there was lower incidence rates of CMV disease, EBV infection, shorter durations of CMV infection and better survival in CD3+CD4+ T cell >100/µl group as compared with ≤100/µl group. CONCLUSION: CD3+CD4+ T cell count is a good predictor for CMV and EBV infection after allo-HSCT in SAA patients. There are low risk of infe-ctions from CMV and EBV when CD3+CD4+ T cell count >100/µl in any time after transplant, which means lower occurrence of CMV and EBV infection and better survival when CD3+CD4+ T cell counts is >100/µl in 3 months after transplant in SAA patients.


Assuntos
Anemia Aplástica/terapia , Linfócitos T CD4-Positivos , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/imunologia , Complexo CD3 , Citomegalovirus , Infecções por Citomegalovirus/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Humanos
17.
J Hematol Oncol ; 10(1): 25, 2017 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-28107815

RESUMO

BACKGROUND: Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients. METHODS: We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled. RESULTS: Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9-20) and 11 (range, 8-19) days, with a cumulative incidence of 97.8 and 97.1% (P = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II-IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P < 0.001), grades III-IV aGVHD (10.1 vs. 1.5%, P = 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P < 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P = 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (P = 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (P = 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type. CONCLUSIONS: Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade/imunologia , Adolescente , Adulto , Anemia Aplástica/complicações , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/imunologia , Haploidia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
18.
Br J Haematol ; 175(2): 265-274, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27352174

RESUMO

We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Haplótipos , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Adolescente , Adulto , Anemia Aplástica/etiologia , Anemia Aplástica/mortalidade , Biomarcadores , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retratamento , Índice de Gravidade de Doença , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(6): 1576-81, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26708874

RESUMO

OBJECTIVE: To investigate the effect of RYBP gene on sensitivity of HL-60 cells to chemotherapy drugs by using RNA interference. METHODS: Plasmid expressing RYBP specific shRNA was constructed and then was used to establish the RYBP knockdown stable HL-60 cell line. Q-PCR and Western blot were used to confirm the efficacy of RYBP gene silencing at mRNA and protein level respectively; then the DNA ladder and Annexin V labeled flow cytometry were used to detect cell apoptosis; CCK-8 was used detect the sensitivity of HL-60 cells to the chemotherapeutic drug cytarabine or daunorubicin. RESULTS: The lentiviral-RYBP-shRNA vector was succesfully and effectively inhibit the expression of RYBP at mRNA and protein in HL-60 cells. It was found that without chemotherapy drug treatment the apoptosis rate of RYBP shRNA group was lower than that of the empty vector control group (NC group). When treated with cytarabine, the apoptosis rate and inhibitive rate of RYBP shRNA group were lower than those of NC group. Besides, when treated with daunorubicin, the apoptosis rate of RYBP shRNA group was lower than that of NC group, while the inhibitive rate had no significant difference. CONCLUSIONS: RYBP gene silencing can inhibitive the apoptosis of HL-60 cells and significantly reduce the sensitivity to cytarabine, but this gene silencing can't affect the sensitivity to daunorubicin.


Assuntos
Interferência de RNA , Apoptose , Vetores Genéticos , Células HL-60 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lentivirus , Plasmídeos , RNA Mensageiro , RNA Interferente Pequeno , Proteínas Repressoras
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 477-80, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948208

RESUMO

OBJECTIVE: To investigate the clinical efficacy of compound Zaofan pill combined with cyclosporine and androgen for treatment of patients with chronical aplastic anemia(CAA), and its effect on bone marrow microvessel density(MVD) and vascular endothelial growth factor(VEGF) of CAA patients. METHODS: A total of 76 cases of CAA were randomly divided into group 1 and group 2, among them the group 1 (38 cases) was treated with cyclosporine and androgen alone, while the group 2(38 cases) was treated with compound Zaofan pill combined with cyclosporine and androgen. Samples of 20 cases with normal bone marrow were used as controls. The clinical effects of each groups were observed, and the mean bone marrow MVD and VEGF levels were detected before and after half a year's treatment. RESULTS: The mean bone marrow MVD and VEGF levels in CAA group before treatment were significantly lower than that in normal control group, but bone marrow MVD and VEGF levels in 2 groups significantly increased after treatment. Group 1 showed the cure and response rate of 15.8%, while group 2 showed the cure and response rate of 44.7%, there was significant difference between the two groups (P<0.05)). There was no significant difference of bone marrow MVD and VEGF expression before treatment between group 1 and group 2. After treatment, bone marrow MVD and VEGF expression of group 2 were significantly higher than pre-treatment, moreover the bone marrow MVD and VEGF expression in group 2 were significantly higher than that in group 1. CONCLUSIONS: The compound Zaofan pill combined with cyclosporine and androgen can obviously increase the levels of MVD and VEGF in bone marrow, and improve the efficacy of treatment in CAA patients.


Assuntos
Anemia Aplástica , Medula Óssea , Ciclosporina , Humanos , Fator A de Crescimento do Endotélio Vascular
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