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1.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

2.
Chin Med J (Engl) ; 134(12): 1431-1440, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34091525

RESUMO

BACKGROUND: The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes. METHODS: A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs). RESULTS: The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88-40.30, P < 0.001), which was an independent risk factor for increased NRM (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001) and inferior OS (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001). CONCLUSIONS: These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure, leading to a risk of post-CCVD. Post-CCVD was a powerful predictor for high NRM and inferior OS. Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.


Assuntos
Transtornos Cerebrovasculares , Transplante de Células-Tronco Hematopoéticas , Transtornos Cerebrovasculares/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Autólogo
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 9-16, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554790

RESUMO

OBJECTIVE: To analyze the relationship between the expression level of SQLE and the prognosis of patients with acute myeloid leukemia (AML) through large sample data. METHODS: The data of genome, transcriptome, gene chip expression, and clinical information were statistically analyzed in multiple cohorts of AML patients with large samples. RESULTS: It was found that the expression level of SQLE gene in tumor cells of AML patients was significantly higher than that of healthy controls (P=0.001). In the three AML corhort, the SQLE high expression group showed a worse therapeutic outcome (OS, P=0.009, P=0.0001, P=0.006; EFS, P=0.005, P=0.001). The unvariate and multivariate survival prognosis analysis indicated that the high expression of SQLE suggests lower event-free survival rate (EFS, HR=1.551, P<0.05) and overall survival rate (OS, HR=1.484, P<0.05). At the same time, it was also found that among different risk subgroups, the expression of SQLE in high risk group was higher (P<0.001, P=0.01), while the patients with high SQLE expression, who received allogeneic HSCT, had longer overall survival time (P=0.006). CONCLUSION: The up-regulation SQLE expression suggests a poor prognosis for the patients with AML.


Assuntos
Leucemia Mieloide Aguda , Intervalo Livre de Doença , Humanos , Prognóstico , Taxa de Sobrevida , Transcriptoma
4.
J Exp Clin Cancer Res ; 39(1): 278, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298132

RESUMO

BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

5.
Front Pharmacol ; 11: 892, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32625091

RESUMO

Ischemic stroke (IS) is characterized by high morbidity and high mortality. The integration of Traditional Chinese medicine (TCM) and western medicine has shown promising benefits in relieving symptoms, promoting neurological recovery, and improving the quality of life of patients with IS. In TCM, Qi-deficiency along with blood-stasis (QDBS) syndrome is one of the common types of IS that is treated by invigorating Qi and activating blood circulation. In TCM theory, improving the corresponding degree of prescription-syndrome correlation (PSC) is helpful to improve clinical efficacy. In this study, we intend to use similar prescriptions that invigorate Qi and activate blood circulation: Buyang Huanwu granules (BHG), Naoxintong capsules (NXTC), and Yangyin Tongnao granules (YTG). The goal is to evaluate their level of PSC inpatients with IS with QDBS syndrome and find relevant biomarkers to provide an objective basis for precise treatment of TCM and improve the clinical therapeutic effects. A multicenter, randomized, double-blinded, and placebo-controlled intervention trial will be conducted in IS patients with QDBS syndrome, followed by an add-on of Chinese patent medicine. A total of 160 subjects will be randomly assigned to the BHG, NXTC, YTG, and placebo groups in a 1:2:1:1 allocation ratio. All subjects will undergo 28 days of treatment and then followed for another 180 days. The primary outcome is the changes in the National Institutes of Health Stroke Scale score after 28 days of medication. The secondary outcomes include the modified Rankin scale score, activity of daily living scale score, and TCM symptom score. Data will be analyzed in accordance with a predefined statistical analysis plan. Ethical approval of this trial has been granted by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ID: 2017-Y-004-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1800015189), and the results will be disseminated to the public through peer-reviewed journals and academic conferences.

7.
Medicine (Baltimore) ; 99(23): e20552, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502021

RESUMO

BACKGROUND: To assess the association of the interaction between the rs9619311 and rs402007 polymorphisms and smoking with essential hypertension (EH) in a Chinese Han population. METHOD: Peripheral blood samples were extracted from 422 EH patients and 280 normotensive (NT) patients in a Chinese Han population. A whole blood genomic DNA extraction kit was used to extract genomic DNA from the blood samples. Polymerase chain reaction restriction fragment length polymorphism was used to detect the rs402007 polymorphism of a disintegrin and metalloproteinase with thrombospondin type motifs 1 gene and the rs9619311 polymorphism of the tissue inhibitor of metalloproteinase-3 gene. The distributions of the genotypes and alleles between the 2 study groups (EH and NT) were compared. The main risk factors for EH were determined by using logistic regression analysis. The effects of gene-gene and gene-smoking interactions on EH were analyzed using multifactor dimensional reduction. RESULTS: The frequencies of the rs402007 GC + CC genotype and the C allele were significantly different between the EH and NT groups (0.68 vs 0.57, χ = 8.99, P = .003, odds ratio [OR] = 1.19; 0.45 vs 0.32, χ = 22.16, P < .001, OR = 1.38). The frequencies of the rs9619311 TC + CC genotype and the C allele were also significantly different between the 2 groups (0.33 vs 0.25, χ = 4.51, P = .04, OR = 1.44; 0.18 vs 0.13, χ = 7.03, P = .01, OR = 1.50). Logistic regression analysis suggests that the rs402007 and rs9619311 polymorphisms are independent risk factors for EH (OR = 2.37, 1.86; P < .001, respectively). The multifactor dimensionality redundant analysis results showed that the interaction among rs402007, rs9619311, and smoking was statistically significant (P = .001). CONCLUSIONS: A disintegrin and metalloproteinase with thrombospondin type motifs 1 rs402007 and tissue inhibitor of metalloproteinase-3 rs9619311 polymorphisms are associated with EH in a Chinese Han population, and there was a positive interaction among rs402007, rs9619311, and smoking.


Assuntos
Proteína ADAMTS1/genética , Hipertensão Essencial/genética , Grupos Étnicos/genética , Predisposição Genética para Doença , Polimorfismo Genético , Fumar/epidemiologia , Inibidor Tecidual de Metaloproteinase-3/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Hipertensão Essencial/epidemiologia , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 377-384, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319366

RESUMO

OBJECTIVE: To investigate the clinical and prognostic value of SLC25A12 in patients with acute myeloid leukemia (AML). METHODS: The expression levels of SLC25A12 in bone marrow or peripheral blood cells of AML patients and healthy people in two independent cohorts (n=46, n=290, respectively) were compared. Then it was assessed that the prognostic value of SLC25A12 expression in two independent AML study cohorts (n=163, n=329, respectively) by mean of integrated analysis of genomic, transcriptome, clinical and prognosis information. RESULTS: The expression of SLC25A12 in AML patients significantly increased as compared with that of healthy people (P=0.0001, P=0.0238, respectively). Univariate and multivariate analyze showed that high SLC25A12 expression was significantly associated with shorter event-free survival (EFS)(HR=1.605, P=0.018) and overall survival (OS)(HR=1.818, P=0.002) of patients. In favorable-risk and intermediate-risk subgroups, patients with high SLC25A12 expression showed shorter EFS and OS than patients with low SLC25A12 expression. CONCLUSION: High SLC25A12 expression significantly associated with poor prognosis of AML patients, which suggests that SLC25A12 aberrant expression can be used as a potential molecular marker for prognosis evaluation of AML patients.


Assuntos
Leucemia Mieloide Aguda , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Medula Óssea , Intervalo Livre de Doença , Humanos , Prognóstico , Transcriptoma
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 7-11, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027245

RESUMO

OBJECTIVE: To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis. METHODS: A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed. RESULTS: The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01). CONCLUSION: The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.


Assuntos
Leucemia Mieloide Aguda , Fator de Processamento U2AF/genética , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico , Indução de Remissão
10.
Ann Transplant ; 24: 328-340, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31171762

RESUMO

BACKGROUND Allogeneic transplantation remains one of the best therapies for high-risk acute myeloid leukemia (HR-AML). MATERIAL AND METHODS This study retrospectively analyzed 126 patients with HR-AML after allogeneic hematopoietic stem cell transplantation (allo-HCST). RESULTS The disease-free survival (DFS) rates of 1 year and 3 years were 58.83% (95%CI: 50.75-68.20%) and 53.09% (95%CI: 44.59-63.22%) respectively. The cumulative relapse rates of 1 year and 3 years were 21.1% (95%CI: 14.4-28.8%) and 25.9% (95%CI: 18.1-34.5%) respectively. The cumulative incidences of III to IV acute graft-versus-host disease (aGVHD) for 100 days was 8.70% (95%CI: 4.6-14.5%). The cumulative rate of extensive chronic graft-versus-host disease (cGVHD) for 1-year was 4.1% (95%CI: 1.5-8.7%). The cumulative transplantation related mortality rate of 1 year and 3 years were 20.1% (95%CI: 13.6-27.6%) and 21.0% (95%CI: 14.3-28.6%) respectively. Univariate analysis revealed that lower overall survival was correlated with age, bacterial or fungal infection, disease status at transplantation, III-IV aGVHD, post-transplantation lymphoproliferative disorders (PTLD), white blood cell engraftment, and extramedullary involvement (P<0.05). The results of multivariate analysis were that the aforementioned factors were also related to lower overall survival except for PTLD (P<0.05). The results of univariate and multivariate analysis were that extramedullary involvement, III-IV aGVHD, and status pre-transplantation influenced DFS (P<0.05). The risk factors for relapse were status pre-transplantation and extramedullary involvement by univariate and multivariate analysis (P<0.05). CONCLUSIONS HR-AML has inferior prognosis. Our study indicated the necessity of achieving remission status prior to hematopoietic stem cell transplantation, and administration of preventive treatments on high-risk patients after hematopoietic stem cell transplantation. In addition, adequate prevention and treatment of complications are needed.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
11.
Ann Transplant ; 24: 175-184, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30940797

RESUMO

BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following solid organ transplantation and allogeneic hematopoietic stem cell transplantation (Allo-HSCT), which gives rise to high mortality rates. MATERIAL AND METHODS This was a single-center retrospective analysis based on 27 patients who were diagnosed with PTLD following Allo-HSCT between January 1, 2007 and June 2018 at the Chinese PLA General Hospital. The purpose of this analysis was to investigate responses and prognostic factors of rituximab-based treatment. RESULTS Twenty-seven patients were treated with rituximab. Among them, 20 of 27 patients (74.07%) had a complete response, 2 of 27 patients (7.41%) had a partial response, 5 of 27 patients (18.52%) had no response, and 22 of 27 patients (81.48%) cleared Epstein-Barr virus (EBV) copies. There were no obvious side effects. The 1-year overall survival (OS) estimate was 46.8% (95% CI, 23.1-65.5%). Univariate analysis revealed that lower OS was correlated with Eastern Cooperative Oncology Group (ECOG) score standard (3-4), Epstein-Barr virus (EBV) viral load (≥106 copies/mL), bacteria or fungal infection, and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab (P<0.05). Multivariate analysis showed that each of the following were independently associated with lower OS (P<0.05): female, ECOG score standard (3-4), and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab. CONCLUSIONS Our results demonstrated that rituximab-based treatment was a safe and effective strategy for patients who were diagnosed with PTLD following Allo-HSCT. The identified prognostic factors may help to detect which PTLD patients are at a higher risk of mortality.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Rituximab/uso terapêutico , Adolescente , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Criança , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Carga Viral , Ativação Viral , Adulto Jovem
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 911-916, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950242

RESUMO

OBJECTIVE: To analyze the infection characteristics of sputum and venous blood pathogen in the patients with hematological malignancies and respiratory symptom in the Hematology Department in tropical region and to investigate its drug-resistance so as to provide etiological evidence for clinical treatment. METHODS: The pathogens and their drug-resistance of 2466 samples in the patients with hematological malignancies and respiratory symptom in the Department were analyzed retrospectively from January 2013 to November 2017. The samples were collected from sputum and venous blood. RESULTS: The sputum sample culture in patients with hematologic diseases showed that 224 strains were isolated, out of them 98 strains (43.75%) were fungi mainly candida albicans (41 strains); and then 88 Gram-negative strains (39.28%), among them the main pathogenic bacteria were Escherichia coli(22 strains) and klebsiella Klebsiella pneumoniae(12 strains); and then 38 Gram-positive strains (16.96%), among them the main pathogeni-bacteria were Enteroccocus (14 strains) and Gram-positive bacilli (14 strains). The blood samples culture of patients with hematologic diseases showed that 61 strains were isolated, out of them the isolated rate of Gram-positive bactetia was higherst, which accounted for 55.74%(34/61), mainly including staphylococcus lominis (19 strains); and the isolated rate of Gram-negative bacteria was 44.26% (27/61), among them main pathogenic bacteria was Klebsiella pneumoniae (12 strains). The resistance test of pathogenic bacteria to drugs showed that the resistant rate of Gram-negative bacteria to tigecycline, imipenem and atl-962 duenner was lowest, while the Gram-positive pathogenic bacteria such as Enterococcus, Gram-positive bacilli and Staphylococcus aureus were sensitive to vancomycin, tigecycline and linezolid was high. CONCLUSION: the patients in hematology department are infected easily in the hospital in tropical region. The main pathogens are fungal strains in the respiratory tract of patients with hematological malignancy according to the sputum culture results. The clinician in tropical regions should choose suitable antibiotics for anti-infective therapy, which is different from the situation in North China or other northern areas.


Assuntos
Candidíase , Bactérias , Infecções Bacterianas , Candida , China , Farmacorresistência Bacteriana , Neoplasias Hematológicas , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
13.
Chin Med J (Engl) ; 131(7): 790-798, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29578122

RESUMO

Background: Studies of haploidentical-related donor (HRD) stem cell transplantation using a combination of peripheral blood stem cells (PBSCs) and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia (AML). Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation (HRD-PBSCT) for relapsed/refractory AML were analyzed. Methods: We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs (n = 36). Results: Thirty-one (86.1%) patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease (aGVHD) in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation (range: 10-1700 days), reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age >40 years were independent risk factors for inferior disease-free survival or overall survival (P < 0.05). The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available. Conclusions: Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.


Assuntos
Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Incidência , Masculino , Análise Multivariada , Estudos Retrospectivos
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(4): 980-986, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28823255

RESUMO

OBJECTIVE: To summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China. METHODS: The factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression. RESULTS: The immune type of t(8;21) AML patients was mainly with HLA-DR+, CD117+, CD34+, MPO+, CD38+, CD13+ and CD33+ (>95%), part of them with CD19+ and CD56+; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×109/L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×109/L(P<0.05). CONCLUSION: The clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×109/L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.


Assuntos
Leucemia Mieloide Aguda , China , Antígenos HLA-DR , Humanos , Prognóstico , Estudos Retrospectivos
15.
Br J Haematol ; 176(1): 92-100, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27714774

RESUMO

The features of graft-versus-host disease (GVHD) were compared between patients who underwent myeloablative conditioning and received a peripheral blood stem cell transplant (PBSCT) from either a haploidentical donor (HID) or a matched sibling donor (MSD) during the same period of time. The HID group included more patients with advanced disease. Both groups received the same GVHD prophylaxis with the addition of antithymoglobulin (ATG) in HID group. Higher cumulative incidences (CI) of acute GVHD grade 2-4 (35·1% vs. 13·9%, P = 0·003), similar CI of grade 3-4 (14·5% vs. 9·8%, P = 0·595), less 3-year CI of extensive chronic GVHD (17·1% vs. 41·5%, P = 0·017) and less severe chronic GVHD (5·8% vs. 21·2%, P = 0·049) occurred in the HID group compared with the MSD group. There was no difference in the sites of the involved organs between these two groups. Higher 3-year CI of non-relapse mortality (24·0% vs. 10·2%, P = 0·014), relapse (39·0% vs. 22·6%, P = 0·032) and inferior disease-free survival (45·7% vs. 78·9%, P = 0·000) were recorded in the HID cohort compared with the MSD group. More HID patients had Karnofsky scores above 90 than those in MSD group (P = 0·016). In conclusion, ATG plays a key role in the unmanipulated HID PBSCT protocol, producing better quality of life in survivors.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/terapia , Histocompatibilidade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adolescente , Adulto , Soro Antilinfocitário/uso terapêutico , Criança , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Incidência , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Qualidade de Vida , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Adulto Jovem
16.
Acta Haematol ; 136(4): 201-209, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27640088

RESUMO

BACKGROUND: The survival of patients with acute myeloid leukemia (AML) with t(8;21) was reported to be shorter in China than in other countries. PATIENTS: We analyzed the correlation between different cytarabine (Ara-c) regimens and outcome in 255 t(8;21) AML patients in China who received postremission consolidation chemotherapy only. RESULTS: The 5-year overall survival (OS) of the high-dose Ara-c group (HDAC; 2≤ Ara-c ≤3 g/m2), intermediate-dose Ara-c group (MDAC; 1.0≤ Ara-c <2.0 g/m2), low-dose Ara-c group (LDAC; 0.2< Ara-c <1.0 g/m2) and standard-dose Ara-c group (SDAC; 0.1≤ Ara-c ≤0.2 g/m2) were 65.3, 39.4, 25.2 and 27.9%, respectively (p = 0.003). In the HDAC group, but not in the MDAC group, the 5-year OS of patients who achieved 3-4 cycles of chemotherapy was superior to those who underwent 1-2 cycles (84.4 vs. 43.6%, p < 0.05), and the 3-year OS of patients who achieved an accumulated 36 g/m2 of Ara-c was significantly higher compared to those who did not (85.3 vs. 39.2%, p < 0.05). Multivariate analysis indicated that factors such as WBC >3.5 × 109/l, PLT ≤30 × 109/l, and extramedullary infiltration were associated with a poor prognosis. CONCLUSION: The survival of t(8;21) AML patients treated with high-dose Ara-c (≥2 g/m2) was superior to other dose levels in postremission consolidation chemotherapy. Patient survival was improved by 3-4 cycles of chemotherapy with an accumulated concentration of 36 g/m2 of Ara-c. WBC >3.5 × 109/l, PLT ≤30 × 109/l and extramedullary infiltration could be indicative of a poor clinical prognosis.


Assuntos
Citarabina/administração & dosagem , Indução de Remissão , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , China , Humanos , Leucemia Mieloide Aguda/induzido quimicamente , Estudos Retrospectivos , Resultado do Tratamento
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(3): 693-7, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27342492

RESUMO

OBJECTIVE: To analyze the clinical manifestations and laboratory features of patients with T large granular lymphocytic leukemia (T-LGLL), so as to improve the understanding of this disease. METHODS: The clinical data of 10 patients with T-LGLL in General Hospital of Chinese PLA from October 2015 to March 2010 were analyzed retrospectively. RESULTS: Their median age at diagnosis was 51 years old. 9/10 (90%) patients showed symptoms of anemia, with a median Hb level of 82.5 g/L, 5/10 (50%) patients combined with autoimmune disorders and with a median Hb level of 77 g/L. 7/10 (70%) patients had splenomegaly, 2/10 (20%) patients had complex karyotype, 2/10 (20%) patients had gene mutations, the median age of 4 patients with complex karyotype and gene mutation was 49 years old, all of them suffered from splenomegaly. The immunophenotype of 6/10 patients was CD3+ CD4- CD8+ and that of 2/10 patients (20%) was CD3+ CD4- CD8-, that of another 2/10 (20%) was CD3+ CD4+ CD8-, the clinical features between different types of immunization were not statistically different. CONCLUSION: T-LGLL patients often are old men, combined with anemia and splenomegaly, often associated with autoimmune diseases; the patients with complex karyotype and gene mutation are younger and they are more with hepatosplenomegaly; the guide role of different immunotypes for clinical strategy is no significant.


Assuntos
Leucemia Linfocítica Granular Grande/diagnóstico , Anemia/patologia , Doenças Autoimunes/patologia , Aberrações Cromossômicas , Hemoglobinas/análise , Humanos , Imunofenotipagem , Leucemia Linfocítica Granular Grande/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Baço/patologia
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 578-82, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948228

RESUMO

The t(8;21)(q22;q22) translocation is the most common chromosomal abnormalities in AML, and the chromosomal translocation forms AML1-ETO. The t(8;21) AML is a heterogeneity disease. It is unclear for how to treat the relapsed or refractory AML. Recently, the clinical trials and pathogenesis have made great progress. This article summarizes the current clinical trials and recruiting t(8;21) AML clinical trials and researches that related to treatment are as followed: epigenetics, JAK/STAT signaling, steroid, Chinese traditional medicine, and interferon. With the progress of pathogenesis researches, more and more treatments will translate into clinical trials, which can provide more optional choice for relapsed or refractory t(8;21) AML. In this article the AML1-ETO structure and t(8;21) AML pathogenesis, the clinical researches of t(8;21) AML treatment and basic researches of t(8;21) AML treatment are summarized.


Assuntos
Cromossomos Humanos Par 22 , Leucemia Mieloide Aguda , Epigênese Genética , Humanos , Translocação Genética
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(1): 12-8, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25687038

RESUMO

OBJECTIVE: This study was aimed to analyze the expression and regulation mechanism of SIRT1 in AML1-ETO positive leukemia to find the core promoter. METHODS: The real-time RT-PCR was used to detect the expression of SIRT1 in AML1-ETO positive leukemia cell line and clinical samples of leukemia patients, a SIRT1 promoter-luciferase reporter vector was constructed and the promoter activity was evaluated in the 293T cell line. A series of possible core promoter fragments of the SIRT1 5'-untranslated region were amplified by PCR, the PCR products were cloned into XhoI/HindIII-digested pGL3-Basic reporter vector, the poly-cationic compound SuperFect reporter vector complexes were transfected into 293T cells.The dual-luciferase Reporter Assay System was used to quantitate the reporter vector luciferase activity. RESULTS: The six kinds of promoter fragment of SIRT1 gene were successfully constructed and cloned into the pGL3-Basic reporter vector, which was authenticated by XhoI/HindIII co-digestion and DNA sequencing. The luciferase activity of the promoter construct was significantly higher than that of the pGL3-Basic promoter in 293T cells. The luciferase report gene assay was also used to detect the regulation of AML1-ETO on the transcription activity of SIRT1 promoter. The results showed that the expression level of SIRT1 increased with the increase mens of AML1-ETO, the promoter of SIRT1 could be bound by AML1-ETO. CONCLUSION: The SIRT1 promoter-luciferase reporter vector is successfully constructed, the transfection system used in this study can effectively transfer gene in 293T cells. The SIRT1 core promoter possesses higher activity in 293T cells and can promote significantly expression of luciferase reporter gene in 293T cells. The transcription regulation of AML1-ETO on SIRT1 is carried out via promoting its promoter activity.


Assuntos
Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Linhagem Celular , Subunidade alfa 2 de Fator de Ligação ao Core , Genes Reporter , Vetores Genéticos , Humanos , Leucemia , Luciferases , Proteínas de Fusão Oncogênica , Proteína 1 Parceira de Translocação de RUNX1 , Sirtuína 1 , Transcrição Genética , Transfecção
20.
Hematol Oncol ; 33(2): 80-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24519469

RESUMO

Information regarding the characteristics of pleural effusions in patients with POEMS syndrome is limited. The aim of this study was to describe the incidence and risk factors of pleural effusions in patients with POEMS syndrome and characterize the pleural fluid biochemistry in those patients. A retrospective review of 96 patients with POEMS syndrome was conducted. The patients were divided into groups with and without pleural effusions. The clinical data were obtained from medical charts. Risk factors were studied with univariate and multivariate analysis. The median age at the time of diagnosis of POEMS syndrome was 45.1 years, and the median disease duration was 30.4 months. Pleural effusions were detected in 41 (42.7%) of the 96 patients. Increased serum vascular endothelial growth factor (VEGF), complement component 3 (C3), Lambda light chain, tumour necrosis factor (TNF)-α, interleukin (IL)-6 levels and low albumin as well as cardiac disease were found to be significantly correlated with pleural effusions. By multivariate logistic regression, independent risk factors for pleural effusions in POEMS syndrome were VEGF [odds ratio (OR): 2.46, 95% confidence interval (CI): 1.720-3.414, p = 0.01], TNF-α (OR: 3.64, 95% CI: 1.073-4.338, p = 0.04) and C3 (OR: 3.77, 95% CI: 1.225-3.591, p = 0.02) levels. Pleural effusions are the most common thoracic involvement findings in patients with POEMS syndrome, and all the pleural fluids are exudates. Serum VEGF, TNF-α and C3 levels are identified as important risk factors for presence of pleural effusions in POEMS syndrome.


Assuntos
Síndrome POEMS/complicações , Derrame Pleural/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Ascite/epidemiologia , Biomarcadores , Doenças Cardiovasculares/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Exsudatos e Transudatos/química , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/epidemiologia , Derrame Pleural/etiologia , Estudos Retrospectivos , Fatores de Risco , Fumar/epidemiologia , Adulto Jovem
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