31 results on '"Xiebing Bao"'
Search Results
2. Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia
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Zhiyu Zhang, Jiayi Huang, Zhibo Zhang, Hongjie Shen, Xiaowen Tang, Depei Wu, Xiebing Bao, Guoqiang Xu, and Suning Chen
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AML ,Omics ,Biomarker ,Risk stratification ,Targeted therapy ,Venetoclax ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Acute myeloid leukemia (AML) is the most frequent leukemia in adults with a high mortality rate. Current diagnostic criteria and selections of therapeutic strategies are generally based on gene mutations and cytogenetic abnormalities. Chemotherapy, targeted therapies, and hematopoietic stem cell transplantation (HSCT) are the major therapeutic strategies for AML. Two dilemmas in the clinical management of AML are related to its poor prognosis. One is the inaccurate risk stratification at diagnosis, leading to incorrect treatment selections. The other is the frequent resistance to chemotherapy and/or targeted therapies. Genomic features have been the focus of AML studies. However, the DNA-level aberrations do not always predict the expression levels of genes and proteins and the latter is more closely linked to disease phenotypes. With the development of high-throughput sequencing and mass spectrometry technologies, studying downstream effectors including RNA, proteins, and metabolites becomes possible. Transcriptomics can reveal gene expression and regulatory networks, proteomics can discover protein expression and signaling pathways intimately associated with the disease, and metabolomics can reflect precise changes in metabolites during disease progression. Moreover, omics profiling at the single-cell level enables studying cellular components and hierarchies of the AML microenvironment. The abundance of data from different omics layers enables the better risk stratification of AML by identifying prognosis-related biomarkers, and has the prospective application in identifying drug targets, therefore potentially discovering solutions to the two dilemmas. In this review, we summarize the existing AML studies using omics methods, both separately and combined, covering research fields of disease diagnosis, risk stratification, prognosis prediction, chemotherapy, as well as targeted therapy. Finally, we discuss the directions and challenges in the application of multi-omics in precision medicine of AML. Our review may inspire both omics researchers and clinical physicians to study AML from a different angle.
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- 2024
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3. High FAAP24 expression reveals poor prognosis and an immunosuppressive microenvironment shaping in AML
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Xiebing Bao, Jingyun Chi, Yiwei Zhu, Minfeng Yang, Jiahui Du, Zaixiang Tang, Xiaogang Xu, Genxiang Mao, Zhibing Wu, Jun Chen, Jingsheng Hua, Ting Xu, and Song-Bai Liu
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FAAP24 ,AML ,Prognosis ,Immunosuppression ,Chelerythrine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background As a core member of the FA complex, in the Fanconi anemia pathway, FAAP24 plays an important role in DNA damage repair. However, the association between FAAP24 and patient prognosis in AML and immune infiltration remains unclear. The purpose of this study was to explore its expression characteristics, immune infiltration pattern, prognostic value and biological function using TCGA-AML and to verify it in the Beat AML cohort. Methods In this study, we examined the expression and prognostic value of FAAP24 across cancers using data from TCGA, TARGET, GTEx, and GEPIA2. To further investigate the prognosis in AML, development and validation of a nomogram containing FAAP24 were performed. GO/KEGG, ssGSEA, GSVA and xCell were utilized to explore the functional enrichment and immunological features of FAAP24 in AML. Drug sensitivity analysis used data from the CellMiner website, and the results were confirmed in vitro. Results Integrated analysis of the TCGA, TARGET and GTEx databases showed that FAAP24 is upregulated in AML; meanwhile, high FAAP24 expression was associated with poor prognosis according to GEPIA2. Gene set enrichment analysis revealed that FAAP24 is implicated in pathways involved in DNA damage repair, the cell cycle and cancer. Components of the immune microenvironment using xCell indicate that FAAP24 shapes an immunosuppressive tumor microenvironment (TME) in AML, which helps to promote AML progression. Drug sensitivity analysis showed a significant correlation between high FAAP24 expression and chelerythrine resistance. In conclusion, FAAP24 could serve as a novel prognostic biomarker and play an immunomodulatory role in AML. Conclusions In summary, FAAP24 is a promising prognostic biomarker in AML that requires further exploration and confirmation.
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- 2023
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4. Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia
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Peng Ke, Jundan Xie, Ting Xu, Meiyu Chen, Yusha Guo, Ying Wang, Huiying Qiu, Depei Wu, Zhao Zeng, Suning Chen, and Xiebing Bao
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venetoclax resistance ,senescence ,prognosis ,acute myeloid leukemia ,immunotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundSatisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence.MethodsHere, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes.ResultsAccording to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model’s risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines.ConclusionsThe 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis.
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- 2023
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5. Development of a Nomogram for Predicting the Cumulative Incidence of Disease Recurrence of AML After Allo-HSCT
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Tongtong Zhang, Xiebing Bao, Huiying Qiu, Xiaowen Tang, Yue Han, Chengcheng Fu, Aining Sun, Changgeng Ruan, Depei Wu, Suning Chen, and Yang Xu
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allogeneic hematopoietic cell transplant ,acute myeloid leukemia ,predictive mutations ,gene mutation topography ,cumulative incidence of relapse ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Using targeted exome sequencing, we studied correlations between mutations at diagnosis and transplant outcomes in 332 subjects with acute myeloid leukemia (AML) receiving allotransplantation. A total of 299 patients (299/332, 90.1%) had at least one oncogenic point mutation. In multivariable analyses, pretransplant disease status, minimal residual disease (MRD) before transplantation (pre-MRD), cytogenetic risk classification, and TP53 and FLT3-ITDhigh ratio mutations were independent risk factors for AML recurrence after allotransplantation (p < 0.05). A nomogram for the cumulative incidence of relapse (CIR) that integrated all the predictors in the multivariable model was then constructed, and the concordance index (C-index) values at 6, 12, 18, and 24 months for CIR prediction were 0.754, 0.730, 0.715, and 0.690, respectively. Moreover, calibration plots showed good agreements between the actual observation and the nomogram prediction for the 6, 12, 18, and 24 months posttransplantation CIR in the internal validation. The integrated calibration index (ICI) values were 0.008, 0.055, 0.094, and 0.136 at 6, 12, 18, and 24 months posttransplantation, respectively. With a median cutoff score of 9.73 from the nomogram, all patients could be divided into two groups, and the differences in 2-year CIR, disease-free survival (DFS), and overall survival (OS) between these two groups were significant (p < 0.05). Taken together, the results of our study indicate that gene mutations could help to predict the outcomes of patients with AML receiving allotransplantation.
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- 2021
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6. Comprehensive analysis of ERCC3 prognosis value and ceRNA network in AML
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Xiebing Bao, Yao Chen, Xiao Lou, Jiahui Du, Huijun Li, Nian Liu, Zaixiang Tang, Jingsheng Hua, Weiqiang Guo, and Song-Bai Liu
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Cancer Research ,Oncology ,General Medicine - Abstract
Acute myeloid leukemia (AML) is a hematological malignancy with high molecular and clinical heterogeneity, and is the most common type of acute leukemia in adults. Due to limited treatment options, AML is prone to relapse and has a poor prognosis. Excision repair cross-complementing 3 (ERCC3) is an important member of nucleotide excision repair (NER) that is overexpressed in types of solid cancers and potentially regarded as a prognostic factor. However, its role in AML remains unclear. The purpose of this study was to explore ERCC3 expression and functions in AML.The Cancer Genome Atlas (TCGA) and GEO (Gene Expression Omnibus) were used to test the accuracy of ERCC3 expression levels for AML diagnosis. Using online databases and R packages, we also explored the signaling pathway, epigenetic regulation, infiltration of immune cells, clinical prognostic value, and ceRNA network in AML.Our results revealed that ERCC3 expression was increased in AML and that high ERCC3 expression had good value for disease-free survival and overall survival in AML patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that ERCC3 and co-expressed genes were mainly involved in chemical carcinogenesis/reactive oxygen species, ubiquitin-mediated protein degradation and oxidative phosphorylation. In addition, almost all the mThis study demonstrated that ERCC3 was overexpressed in AML and that high ERCC3 expression can be considered a biomarker conducive to allo-HSCT in AML patients.
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- 2022
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7. LPCAT3 is a potential prognostic biomarker and may be correlated with immune infiltration and ferroptosis in acute myeloid leukemia: a pan-cancer analysis
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Peng Ke, Xiebing Bao, Chenxi Liu, Biqi Zhou, Mengjia Huo, Yanxin Chen, Xing Wang, Depei Wu, Xiao Ma, Dan Liu, and Suning Chen
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Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging - Published
- 2022
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8. Identification of a venetoclaxresistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia.
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Peng Ke, Jundan Xie, Ting Xu, Meiyu Chen, Yusha Guo, Ying Wang, Huiying Qiu, Depei Wu, Zhao Zeng, Suning Chen, and Xiebing Bao
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ACUTE myeloid leukemia ,DISEASE risk factors ,IMMUNOSENESCENCE ,CD14 antigen ,OLDER patients ,PROGNOSTIC models ,GENES - Abstract
Background: Satisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence. Methods: Here, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6- senescence genes. Results: According to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model's risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines. Conclusions: The 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Venetoclax with Decitabine as Frontline Treatment For Younger Adults with Newly Diagnosed ELN Adverse-Risk Acute Myeloid Leukemia: A Single-Arm, Multicenter, Phase 2 Study
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Jundan Xie, Xiaofei Yang, Xiebing Bao, Shengli Xue, Hongjie Shen, Jiannong Cen, Li Yao, Jinlan Pan, Mingqing Zhu, Dandan Liu, Xiaohui Hu, Qian Wu, Jingren Zhang, Haiping Dai, Yanglin Cao, Xuefeng He, Xiaowen Tang, Aining Sun, Ying Wang, Jianhong Fu, Huiying Qiu, Suning Chen, and Depei Wu
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- 2023
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10. Lineage switch from acute myeloid leukemia to acute lymphoblastic leukemia
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Lihong, Zong, Jundan, Xie, Jinyu, Kong, Xiebing, Bao, Xiaoxia, Wu, Yan, Pu, Jian, Zhang, and Huiying, Qiu
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Leukemia, Myeloid, Acute ,Cancer Research ,Oncology ,Acute Disease ,Humans ,Cell Lineage ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma - Published
- 2022
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11. The time-dependent effects of early-onset Epstein-Barr viremia on adult acute leukemia patients following allo-HSCT with ATG-containing MAC regimen
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Depei Wu, Xiebing Bao, Xiao Ma, Feng Chen, Huiying Qiu, Zhengzheng Fu, Suning Chen, Xinyou Zhang, Xiaowen Tang, Yue Han, Qian Zhu, Song-Bai Liu, Peng Ke, and Jihao Zhou
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Adult ,Male ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,medicine.medical_specialty ,Time Factors ,Transplantation Conditioning ,T-Lymphocytes ,medicine.medical_treatment ,Cytomegalovirus ,Graft vs Host Disease ,Viremia ,Hematopoietic stem cell transplantation ,Gastroenterology ,MAC Regimen ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Cumulative incidence ,Antilymphocyte Serum ,Proportional Hazards Models ,Acute leukemia ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,General Medicine ,Myeloablative Agonists ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Allografts ,Prognosis ,medicine.disease ,Transplantation ,Leukemia, Myeloid, Acute ,Regimen ,Histocompatibility ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Female ,Virus Activation ,Unrelated Donors ,business ,Immunosuppressive Agents ,030215 immunology - Abstract
Epstein-Barr virus (EBV) viremia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the impacts of early-onset EBV viremia in acute leukemia (AL) patients who underwent allo-HSCT with anti-thymocyte globulin (ATG)-containing myeloablative conditioning (MAC) regimen. Two hundred and ninety-six patients were included between January 2013 and December 2015. In 126 patients (42.6%) who developed early-onset EBV viremia, with a median time of 48 (range 18~99) days after allo-HSCT. The cumulative incidence of EBV viremia at 30 and 90 days after allo-HSCT were 4.1 and 39.9%, respectively. Prognostic analysis showed that the adjusted overall survival in early-EBVpos group was significantly lower than early-EBVneg group within the first 26.7 months after allo-HSCT [hazard ratio (HR), 1.63, P = 0.012], but significantly higher than those afterward (after 26.7 months: HR 0.11, P = 0.035); for the adjusted event-free survival, early-EBVpos group was significantly inferior in early-EBVpos group within the first 10.8 months after transplantation (HR: 1.55, P = 0.042), and this adverse effect was not detected any more after 10.8 months (HR: 0.58, P = 0.107). Compared with early-EBVneg group after adjusting by aGVHD and CMV viremia, HR for death from transplant-related mortality was 2.78-fold higher in patients with early-EBV viremia in piecewise constant Cox analysis (P = 0.006), and this adverse effect was not detected any more after the cut-point time (HR: 0.67, P = 0.361). No differences in terms of relapse and relapse mortality were observed between early-EBVpos and early-EBVneg group (P > 0.05). In conclusion, the impacts on transplant outcomes of early-EBV viremia were time-dependent, which may help to optimize management strategies for early-EBV viremia after allo-HSCT, especially in AL patients with ATG-containing MAC regimen.
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- 2021
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12. Allogeneic Donor-Derived Anti-CD19 CAR T Cell Is a Promising Therapy for Relapsed/Refractory B-ALL After Allogeneic Hematopoietic Stem-Cell Transplantation
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Xiebing Bao, Lili Zhou, Miao Miao, Yue Han, Weiqing Qian, Huiying Qiu, Jingsheng Hua, Jian Zhang, Caixia Li, Zhengzheng Fu, Depei Wu, and Xiaoxia Wu
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,T-Lymphocytes ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,CD19 ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Prospective Studies ,Child ,Prospective cohort study ,Receptors, Chimeric Antigen ,biology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Chimeric antigen receptor ,Transplantation ,Haematopoiesis ,Cytokine release syndrome ,030220 oncology & carcinogenesis ,biology.protein ,Female ,business ,030215 immunology - Abstract
Introduction Currently, effective and safe salvage therapies are limited among patients with relapsed acute lymphoblastic leukemia after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Anti-CD19 chimeric antigen receptor T (CAR T) cell is a promising treatment. Patients and Methods We studied 11 patients with B-cell acute lymphoblastic leukemia that relapsed after allo-HSCT between September 2017 and October 2019. Patients were treated with a dose of single-infusion donor-derived anti-CD19 CAR T cells. Results Eight patients (72.7%) experienced morphologic remissions. Seven (63.6%) experienced minimal residual disease–negative remission. The ongoing complete remission (CR) duration of 2 patients reached 22 months. The median overall survival was 9 months (range, 2-22 months). Only one patient with grade 1 acute graft-versus-host disease was observed. Two patients (18.2%) developed grade 3/4 cytokine release syndrome. Conclusion This prospective study showed allogeneic donor-derived anti-CD19 CAR T-cell therapy is an effective and safe salvage regimen for patients with relapsed/refractory B-cell acute lymphoblastic leukemia after allo-HSCT. Further randomized and multicenter investigations are needed to evaluate their potential role in relapsed acute lymphoblastic leukemia therapies after allo-HSCT.
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- 2020
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13. Donor CMV-specific cytotoxic T lymphocytes successfully treated drug-resistant cytomegalovirus encephalitis after allogeneic hematopoietic stem cell transplantation
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Juan Zhuang, Xuefeng He, Jihao Zhou, Xiaoli Li, Xiebing Bao, Xinyou Zhang, Depei Wu, Peng Ke, and Xiao Ma
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Adult ,Male ,Ganciclovir ,Foscarnet ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Hematopoietic stem cell transplantation ,Drug resistance ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Antiviral Agents ,03 medical and health sciences ,0302 clinical medicine ,Drug Resistance, Viral ,Humans ,Transplantation, Homologous ,Medicine ,Cytotoxic T cell ,business.industry ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Myeloid leukemia ,Hematology ,Middle Aged ,medicine.disease ,Tissue Donors ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Immunology ,Encephalitis ,Female ,Complication ,business ,T-Lymphocytes, Cytotoxic ,030215 immunology ,medicine.drug - Abstract
Background: Cytomegalovirus (CMV) infection of the central nervous system (CNS) is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Cases presentation: Two patients with drug-resistant CMV encephalitis after allo-HSCT were successfully treated with donor CMV-specific cytotoxic T lymphocytes (CTLs). In the first case, a 27-year-old male who received haploidentical transplantation to treat T-cell acute lymphoblastic leukemia (T-ALL), developed CMV encephalitis during the time of the ganciclovir maintenance treatment. After intravenous foscarnet and donor CMV-specific CTLs, CMV-DNA of CSF became undetectable and the abnormal signs of brain magnetic resonance imaging (MRI) were limited. Another case, a 57-year-old female with acute myeloid leukemia (AML) who underwent haploidentical transplantation, also developed CMV encephalitis during the maintenance treatment of the ganciclovir. After administering donor CMV-specific CTLs intrathecally, the CMV load of the CSF decreased.Conclusions: The intravenous/intratheca administration of donor CMV-specific CTLs may be a safe and effective treatment for CMV encephalitis, especially for patients who suffered from drug-resistant CMV infection.
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- 2020
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14. Combining gene variants with clinical characteristics improves outcome prediction in Chinese patients with myelodysplastic syndromes
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Tongtong Zhang, Hong Liu, Zhao Zeng, Xiebing Bao, Ling Zhang, Suning Chen, Jinlan Pan, Hongjie Shen, Yan Yu, Depei Wu, Yang Hong, Qinrong Wang, and Aining Sun
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China ,Cancer Research ,business.industry ,Myelodysplastic syndromes ,Hematopoietic Stem Cell Transplantation ,Genetic variants ,Hematology ,Prognosis ,medicine.disease ,Bioinformatics ,DNA sequencing ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Myelodysplastic Syndromes ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Risk stratification ,Humans ,Medicine ,business ,Outcome prediction ,Gene ,Proportional Hazards Models ,030215 immunology - Abstract
Genetic variants have been identified in the majority of myelodysplastic syndromes (MDS) patients and have considerably influenced the diagnosis, classification, risk stratification and treatment of MDS. To explore the prognostic significance of genomic variants and build a new prognostic scoring model, we performed next-generation sequencing of 51 known genes in 499 Chinese patients with MDS. Ultimately, the
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- 2019
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15. Central Nervous System Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children
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Peng Ke, Xiaohui Hu, Xinyou Zhang, Xiao Ma, Xiebing Bao, Yuejun Liu, Qian Zhu, Juan Zhuang, Jihao Zhou, Depei Wu, and Shengli Xue
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Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Calcineurin Inhibitors ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Central Nervous System Diseases ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Child ,Retrospective Studies ,business.industry ,Incidence ,Incidence (epidemiology) ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Neurotoxicity ,Infant ,Retrospective cohort study ,Hematology ,General Medicine ,Allografts ,medicine.disease ,Survival Rate ,Calcineurin ,Transplantation ,surgical procedures, operative ,Child, Preschool ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,business ,030215 immunology - Abstract
Central nervous system complications (CNSCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and may be a significant source of morbidity and mortality. We performed a retrospective study of 153 pediatric patients who underwent allo-HSCT to determine CNSC type, incidence, and impact on survival. A total of 34 patients (22.2%) developed CNSCs. The cumulative incidence of CNSCs at 100 days and 3 years was 18.30 and 22.73%, respectively. The most common CNSC was calcineurin inhibitor (CNI)-associated neurotoxicity (50.0%). Risk factors for CNSCs were the time from diagnosis to HSCT ≥4.8 months (p = 0.032) and the development of acute graft-versus-host disease (aGVHD) grade III–IV (p = 0.002). CNSCs after allo-HSCT negatively impacted overall survival (hazard ratio [HR] 1.97, p = 0.043) and nonrelapse mortality (HR 4.84, p < 0.001). In conclusion, CNSCs after allo-HSCT are associated with poor outcomes; patients with severe aGVHD and/or late transplantation should be given more attention.
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- 2019
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16. Genetic Profile and Clinical Implications of PDGFRB Fusion in Adult B-Cell Acute Lymphoblastic Leukemia: A Retrospective Analysis
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De-Pei Wu, Su-ning Chen, Man Wang, Xiebing Bao, Guofa Xu, Zhao Zeng, Jundan Xie, Huiying Qiu, Li-min Liu, and Zhi-bo Zhang
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Oncology ,medicine.medical_specialty ,Text mining ,business.industry ,Internal medicine ,Adult B-Cell Acute Lymphoblastic Leukemia ,Retrospective analysis ,medicine ,PDGFRB ,business ,Genetic profile - Abstract
Background:To investigate the pathogenesis, genetic changes, treatment and prognosis of adult B-cell acute lymphoblastic leukemia (B-ALL) with platelet-derived growth factor receptor B (PDGFRB) fusion. Method:Clinical characteristics, treatment process and prognosis of 7 adult B-ALL patients with PDGFRB fusion were presented respectively, and the PDGFRB fusion was confirmed by fluorescence in situ hybridization, RNA sequencing and Polymerase Chain Reaction. Results: 7 adult B-ALL patients with PDGFRB fusion were presented respectively. There were 5 males and 2 females, with a median age of 21 (range, 17-39) years and a median white blood cell count of 7.85 (range, 2.30-111.25) ×10^9/L. The fusion partners were EBF1, SMIM3 and TERF2. Three of 7 cases received tyrosine kinase inhibitor (TKI) targeted therapy, and 4 of 7 cases received chimeric antigen receptor T -cell (CAR-T) therapy. A total of 6 (85.71%) cases underwent haploid hematopoietic stem cell transplantation (Haplo-HSCT). Overall response rate was 71.43% (4/7), and the common adverse reactions during induction were febrile neutropenia and nausea. Seventy-five percent (3/4) and 100% (6/6) of patients were minimal residual disease negative after CAR-T and Haplo-HSCT. To the last follow-up, 2 of 7 cases relapsed in 2 and 7 months after remission, respectively, and the estimated 36 months of Event-free survival and Overall survival was 75.0% and 66.7%.Conclusions: intensive therapy combined with CAR-T or TKI is needed to achieve deep remission, and sequential Haplo-HSCT may improve the prognosis of adult B-ALL with PDGFRB fusion.
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- 2021
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17. Effect of Timely Lactate Measurement on In-hospital Mortality among Adults with Hypotension and Hyperlactatemia: An Observational Study on Two Cohorts
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Hui Chen, Xiebing Bao, Ying Xu, Yanxia Guo, Mingqin Zhou, Chenyan Zhao, Yao Wei, and Jun Jin
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Background: Whether patients presented with hypotension and hyperlactatemia can benefit from timely lactate measurement and further lactate-guide resuscitation were not fully understood.Methods: This was a retrospective observational study based on the data from the Medical Information Mart for Intensive Care (MIMIC)-III Database and the eICU Collaborative Research Database (eICU). Patients with hypotension (defined as a minimal systolic blood pressure ≤90 mm Hg or minimal mean arterial pressure ≤65 mm Hg or requiring any vasopressors support during the first 24 h after ICU admission) and hyperlactatemia (defined as an initial lactate level > 2.0 mmol/L after ICU admission) were eligible.The primary exposure was the timely lactate measurement, which was defined as an initial lactate level measured within 1 h after ICU admission. The primary outcome was in-hospital mortality. The statistical approaches included multivariate regression, propensity score matching (PSM) and an inverse probability of treatment weighing (IPTW) and causal mediation analysis (CMA) were utilized to elucidate the relationship between timely lactate measurement and in-hospital mortality. Results: A total of 9978 patients were identified, of which 4257 in MIMIC-III and 5721 in eICU. Timely lactate measurement was associated with lower risk-adjusted in-hospital mortality both in MIMIC (OR 0.70 (95%CI 0.58-0.85; pConclusions: Timely lactate measurement is associated with a lower risk-adjusted in-hospital mortality among patients with hypotension and hyperlactatemia, which was proportional mediated through shortening the time to IVF. Delay in initial lactate measurement showed a positive association with in-hospital mortality.
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- 2020
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18. Donor-derived anti-CD19 CAR T cells compared with donor lymphocyte infusion for recurrent B-ALL after allogeneic hematopoietic stem cell transplantation
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Miao Miao, Huiying Qiu, Chengcheng Fu, Xiebing Bao, Depei Wu, Suning Chen, Xiaoxia Wu, Jingsheng Hua, Yue Han, Xinyou Zhang, Jian Zhang, Xiaowen Tang, Lili Zhou, and Caixia Li
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medicine.medical_specialty ,medicine.medical_treatment ,T-Lymphocytes ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,Immunotherapy, Adoptive ,Donor lymphocyte infusion ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Donor derived ,Lymphocytes ,Transplantation ,business.industry ,Anti cd19 ,Hematopoietic Stem Cell Transplantation ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Cytokine release syndrome ,030220 oncology & carcinogenesis ,Lymphocyte Transfusion ,Stem cell ,Car t cells ,business ,030215 immunology - Abstract
The efficacy and safety of donor-derived anti-CD19 CAR T cells vs DLI for the management of relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allo-hematopoietic stem cell transplantation (HSCT) remain unclear. Thirteen B-ALL patients with relapsed after allo-HSCT and thus were treated with donor-derived anti-CD19 CAR T-cell (study group). Fifteen B-ALL patients relapsed after allo-HSCT and thus were treated with DLI (DLI group). The rates of MRD-negative complete remission (61.5%) in the study group were significantly higher than those in the DLI group (13.3%) (p = 0.02). The complete remission duration in study group and DLI group were median 8.0 months (range, 3–25 months) and 4.4 months (range, 1–25 months; p = 0.026), respectively. The overall survival of patients in the study group was superior to that of the DLI group: 9.5 months (range,3–25 months) versus 5.5 months (range, 1–25 months; p = 0.030). One patient with grade 1 acute graft-versus-host disease (aGVHD) was identified in the study group. While five (33.3%) patients in the DLI group developed grades III–IV aGVHD. Three patients (23.07%) developed grade 3 or 4 cytokine release syndrome in the study group. This study suggested that donor-derived anti-CD19 CAR T-cell therapy is promising, safe, and potentially effective for relapsed B-ALL after allo-HSCT and may be superior to DLI.
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- 2020
19. Simplified immune-dysregulation index: a novel marker predicts 28-day mortality of intensive care patients with COVID-19
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Yongsheng Li, Hui Chen, Jun Jin, Xiebing Bao, Jun Wang, and Nan Su
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Oncology ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,China ,Letter ,Coronavirus disease 2019 (COVID-19) ,Critical Care ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,medicine.disease_cause ,Critical Care and Intensive Care Medicine ,Betacoronavirus ,Anesthesiology ,Internal medicine ,Intensive care ,Lymphopenia ,medicine ,Humans ,Pandemics ,Retrospective Studies ,business.industry ,Interleukin-6 ,SARS-CoV-2 ,COVID-19 ,Retrospective cohort study ,Immune dysregulation ,Prognosis ,Intensive Care Units ,ROC Curve ,Area Under Curve ,Cytokines ,28 day mortality ,business ,Coronavirus Infections - Published
- 2020
20. Pattern and prognostic value of <scp>FLT</scp> 3 ‐ <scp>ITD</scp> mutations in Chinese de novo adult acute myeloid leukemia
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Xiebing Bao, Depei Wu, Hongzhi Li, Shengli Xue, Suning Chen, Yao-Hua Song, Yuejun Liu, Qiao-cheng Qiu, Xiao Ma, and Songbai Liu
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Adult ,Male ,FLT3‐ITD ,0301 basic medicine ,FLT3 Internal Tandem Duplication ,China ,Cancer Research ,kinase activity ,acute myeloid leukemia ,Biology ,medicine.disease_cause ,Young Adult ,03 medical and health sciences ,Protein Domains ,Clinical Research ,hemic and lymphatic diseases ,Gene duplication ,medicine ,Humans ,Transplantation, Homologous ,prognostic value ,Kinase activity ,Gene ,Mutation ,Remission Induction ,Myeloid leukemia ,hemic and immune systems ,Adult Acute Myeloid Leukemia ,Original Articles ,General Medicine ,Middle Aged ,Prognosis ,Survival Analysis ,body regions ,Leukemia, Myeloid, Acute ,Mutagenesis, Insertional ,030104 developmental biology ,fms-Like Tyrosine Kinase 3 ,Oncology ,Tandem Repeat Sequences ,Sample Size ,embryonic structures ,Cancer research ,Female ,Original Article ,insertion sites ,Tyrosine kinase ,psychological phenomena and processes ,Stem Cell Transplantation - Abstract
FMS‐like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3‐ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two‐thirds of all FLT3 mutations. The outcome of patients remains unsatisfactory, with low survival rates. It is not yet known whether the different mutations within the FLT3 gene are all associated with patient outcome. In addition, the cause of FLT3‐ITD in‐frame duplication events remains unknown. Although there are some published studies investigating the FLT3‐ITD mutation and its clinical implications in Chinese acute myeloid leukemia (AML) patients, sample sizes tend to be small and detailed molecular profiles of FLT3 mutations are lacking in these studies. In our study, 227 FLT3‐ITD sequences were analyzed from 227 Chinese de novo AML patients. ITD were next classified into 3 types based on molecular profiles of insertion DNA sequences: DNA complete duplication (type I), DNA partial duplication (type II) and complete random sequence (type III). From the 154 patients, we confirmed that high ITD allelic ratio (≥.5) and allogeneic stem cell transplant treatment under CR1 are independent prognostic factors. We also presented evidence that ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations. These findings may help to decipher the mechanisms of FLT3‐ITD in‐frame duplication events and stratify patients when considering different therapeutic combinations.
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- 2018
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21. Impact of FLT3-ITD length on prognosis of acute myeloid leukemia
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Shengli Xue, Jing-Qiu Yu, Hongzhi Li, Zheng Li, Qiao-cheng Qiu, Xiao-Ling Chu, Chao Wang, Xiebing Bao, Ling Li, Haojie Dong, Zixuan Ding, Suning Chen, Xiaowen Tang, Depei Wu, Tao Tao, Song-Bai Liu, and Hongjie Shen
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Myeloid ,business.industry ,Myeloid leukemia ,Mutagenesis (molecular biology technique) ,hemic and immune systems ,Internal tandem duplication ,Hematology ,medicine.disease ,body regions ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,medicine.anatomical_structure ,hemic and lymphatic diseases ,embryonic structures ,Cancer research ,medicine ,Tyrosine ,business ,Survival rate ,psychological phenomena and processes ,030215 immunology ,Flt3 itd - Abstract
The FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) is one of the most frequent mutations found in acute myeloid leukemia (AML) patients, with a frequency of 20–30%. The sizes of ITDs vary dramatically.[1][1] The FLT3 -ITD consists of in-frame insertions of duplicated sequences
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- 2018
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22. Soluble interleukin-27 receptor alpha is a valuable prognostic biomarker for acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation
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Jiaqian Qi, Depei Wu, Xiebing Bao, Jia Chen, Hong Liu, Jingjing Han, Yongsheng Li, Huanle Gong, Shuangzhu Liu, Shoubao Ma, Yang Xu, and Xiaojin Wu
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,lcsh:Medicine ,Kaplan-Meier Estimate ,Hematopoietic stem cell transplantation ,Severity of Illness Index ,Gastroenterology ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,hemic and lymphatic diseases ,Severity of illness ,Humans ,Transplantation, Homologous ,Medicine ,Risk factor ,Child ,lcsh:Science ,Proportional Hazards Models ,Multidisciplinary ,Neutrophil Engraftment ,business.industry ,Proportional hazards model ,Incidence (epidemiology) ,lcsh:R ,Hematopoietic Stem Cell Transplantation ,Receptors, Interleukin ,Middle Aged ,Prognosis ,Transplantation ,030104 developmental biology ,Child, Preschool ,Cytokines ,Female ,lcsh:Q ,business ,Complication ,Biomarkers ,030215 immunology - Abstract
Acute graft-versus-host disease (aGVHD) is a major life-threatening complication after allogeneic haematopoietic stem cell transplantation. Interleukin-27 receptor alpha (IL-27Rα) is a co-receptor of IL-27, an inflammatory cytokine that possesses extensive immunological functions. It has been reported that IL-27Rα can exist in its soluble form (sIL-27Rα) in human serum and can function as a natural IL-27 antagonist. In this study, we examined serum sIL-27Rα levels and evaluated their prognostic value in aGVHD. A total of 152 subjects were prospectively recruited and separated into the training group (n = 72) and the validation group (n = 80). Serum sIL-27Rα at neutrophil engraftment was measured by ELISA. In the training set, a cut-off value of sIL-27Rα = 59.40 ng/ml was identified to predict grade II–IV aGVHD (AUC = 0.735, 95% CI 0.618–0.853, P = 0.001). Cumulative incidences of grade II–IV aGVHD (P = 0.004), relapse rate (P = 0.008), and non-relapse mortality (P = 0.008) in patients with low serum sIL-27Rα (≥59.40 ng/ml) were significantly higher than those of patients with high serum sIL-27Rα (P P = 0.029), IL-10 (R = 0.37, P = 0.0015) and HGF (R = 0.27, P = 0.0208), but was negatively correlated with TNFR1 (R = −0.365, P = 0.0022) and ST2 (R = −0.334, P = 0.0041), elafin (R = −0.29, P = 0.0117), and REG3α (R = −0.417, P = 0.0003). More importantly, the threshold value of sIL-27Rα was then validated in an independent cohort of 80 patients (AUC = 0.790, 95% CI 0.688–0.892, P
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- 2018
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23. Central nervous system complications caused by 3-4 grade aGVHD in adult patients occurred in HLA-mismatched recipients majorly after allogeneic hematopoietic stem cell transplantation
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Xiaojin Wu, Depei Wu, Huiying Qiu, Shengli Xue, Juan Zhuang, Xiebing Bao, Xinyou Zhang, Yuejun Liu, Xiao Ma, Xiaohui Hu, and Peng Ke
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Oncology ,Transplantation ,medicine.medical_specialty ,Adult patients ,business.industry ,medicine.medical_treatment ,Central nervous system ,MEDLINE ,Hematology ,Human leukocyte antigen ,Hematopoietic stem cell transplantation ,Clinical trial ,Text mining ,medicine.anatomical_structure ,Internal medicine ,Medicine ,business ,Survival rate - Published
- 2019
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24. Protective Effect of Rituximab in Chronic Graft-Versus-Host Disease Occurrence in Allogeneic Transplant patients with Epstein Barr Virus Viremia
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Xiebing Bao, Shengli Xue, Jun Lu, Tao Tao, Xiao Ma, Shi-Meng Ji, Depei Wu, and Aining Sun
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medicine.medical_specialty ,medicine.medical_treatment ,Viremia ,Hematopoietic stem cell transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Cumulative incidence ,Hematology ,business.industry ,Incidence (epidemiology) ,Therapeutic effect ,medicine.disease ,Graft-versus-host disease ,030220 oncology & carcinogenesis ,Immunology ,Original Article ,Rituximab ,business ,030215 immunology ,medicine.drug - Abstract
B cells are involved in chronic graft-versus-host disease (cGVHD) pathogenesis, and Rituximab may have a therapeutic effect on cGVHD in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Herein, we retrospectively evaluated the prophylactic effect of Rituximab on cGVHD in a group of Chinese allo-HSCT patients. A total of 102 patients, who suffered Epstein Barr virus (EBV) viremia within 100 days after allo-HSCT, were included in this study. Fifty patients received Rituximab (375 mg/m2 weekly) for EBV viremia, while fifty-two patients did not receive Rituximab. A competing risk model was adopted to compare cumulative incidence of cGVHD, cumulative incidence of relapse (CIR) and transplantation-related mortality (TRM) between two groups. Cumulative incidence of cGVHD in the Rituximab group was lower than in controls (P = 0.0579). Multivariate analyses confirmed that Rituximab was an independent factor for the reduction of cumulative cGVHD incidence (P = 0.0069). No significant difference was observed in CIR (P = 0.39) or TRM (P = 0.48) between two groups and 2-year OS and DFS were comparable (OS, P = 0.667; DFS, P = 0.571). Administration of Rituximab in the early post-transplantation phase may protect against cGVHD in allo-HSCT patients without increasing CIR or TRM.
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- 2017
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25. Anti-CD19 chimeric antigen receptor T-cells induce durable remission in relapsed Philadelphia chromosome-positive ALL with T315I mutation
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Xiebing Bao, Xiaodong Yang, Aining Sun, Xiaoxia Wu, Liqing Kang, Fei Yang, Xiaowen Tang, Huiying Qiu, Zhengzheng Fu, Xiao Ma, Jian Zhang, Deipei Wu, and Lili Zhou
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Cancer Research ,T-Lymphocytes ,Antigens, CD19 ,T315i mutation ,Immunotherapy, Adoptive ,CD19 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Medicine ,Humans ,Philadelphia Chromosome ,Philadelphia Chromosome Positive ,ABL ,Receptors, Chimeric Antigen ,biology ,business.industry ,Anti cd19 ,Ponatinib ,breakpoint cluster region ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Chimeric antigen receptor ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,business ,030215 immunology - Abstract
Effective treatments for relapsed Ph+ALL with T315I mutation are few; CD19 CAR T-cell therapy are a potential therapy for this condition. We reported 7 patients with relapsed Ph+ALL with T315I mutation, who were treated pre- or post-allo-HSCT with CD19-specific CAR T-cells. Of the 7 cases, 6 were in CR or CRp within 1 month after the first infusion of CAR T-cells. MRD revealed a rapid decline in 6 patients. BCR/ABL fusion transcripts were negative in 4/5 cases (not performed in 2). Three patients maintained remission without evidence of MRD by QPCR until the final follow-up, of which 2 received anti-CD19 CAR T-cells and ponatinib at the same time. Our study confirmed the efficacy of anti-CD19 CAR T-cell therapy in treatment of relapsed Ph+ALL with T315I mutation pre- or post-allo-HSCT and the concurrent applicability of this therapy with ponatinib.
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- 2019
26. Prediction of acute GVHD and relapse by metabolic biomarkers after allogeneic hematopoietic stem cell transplantation
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Yiyu Xie, Depei Wu, Shoubao Ma, Yuhan Ji, Jianhua Yu, Yue Han, Chang Wang, Xiaojin Wu, Ahmet Yilmaz, Jinge Xu, Xiebing Bao, Jianying Zhang, Bingyu Yang, Suning Chen, and Hong Liu
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,medicine.medical_treatment ,Palmitic Acid ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Young Adult ,03 medical and health sciences ,immune system diseases ,Predictive Value of Tests ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Metabolomics ,Medicine ,Child ,Hematology ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Odds ratio ,Middle Aged ,Allografts ,Transplantation ,surgical procedures, operative ,030104 developmental biology ,ROC Curve ,Child, Preschool ,Acute Disease ,Biomarker (medicine) ,Female ,Clinical Medicine ,Stem cell ,business ,Biomarkers ,Stearic Acids - Abstract
BACKGROUND There are very few studies investigating metabolic biomarkers to predict acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Metabolic models can provide a framework for analyzing the information-rich omics data sets in this setting. METHODS Four hundred and fifty-six samples from one hundred and fourteen consecutive patients who underwent HSCT from January 2012 to May 2014 were collected for this study. The changes in serum metabolite levels were investigated using a gas chromatography-mass spectrometry-based metabolomics approach and underwent statistical analysis. RESULTS Significant metabolic changes were observed on day 7. The stearic acid/palmitic acid (SA/PA) ratio was effective in the diagnosis of grade II-IV aGVHD. Multivariate analysis showed that patients with high SA/PA ratios on day 7 after HSCT were less likely to develop II-IV aGVHD than patients with low SA/PA ratios (odds ratio [OR] = 0.06, 95% CI 0.02-0.18, P < 0.001). After the adjustment for clinical characteristics, the SA/PA ratio had no significant effect on overall survival (hazard ratio [HR] = 1.95, 95% CI 0.92-4.14, P = 0.08), and patients in the high SA/PA ratio group were significantly more likely to relapse than those in the low ratio group (HR = 2.26, 95% CI 1.04-4.91, P = 0.04). CONCLUSION Our findings suggest that the SA/PA ratio on day 7 after HSCT is an excellent biomarker to predict both aGVHD and relapse. The serum SA/PA ratio measured on day 7 after transplantation may improve risk stratification for aGVHD and relapse after allogeneic stem cell transplantation. FUNDING National Natural Science Foundation of China (81470346, 81773361), Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Natural Science Foundation (BK20161204), Innovation Capability Development Project of Jiangsu Province (BM2015004), Jiangsu Medical Junior Talent Person award (QNRC2016707), and NIH (AI129582 and NS106170).
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- 2018
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27. The impact of FLT3 mutations on treatment response and survival in Chinese de novo AML patients
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Hong Yao, Jing Yang, Shengli Xue, Suning Chen, Jun He, Hong Liu, Zheng Li, Chao Wang, Hongjie Shen, Qiao-cheng Qiu, Song-Bai Liu, Zixuan Ding, and Xiebing Bao
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Oncology ,Sorafenib ,Adult ,Male ,Niacinamide ,Treatment response ,medicine.medical_specialty ,China ,Kaplan-Meier Estimate ,Gene mutation ,Bioinformatics ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Asian People ,Drug Therapy ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Transplantation, Homologous ,Protein Kinase Inhibitors ,business.industry ,Point mutation ,Phenylurea Compounds ,Hematopoietic Stem Cell Transplantation ,hemic and immune systems ,Hematology ,Middle Aged ,Protein-Tyrosine Kinases ,Treatment Outcome ,Activation loop ,fms-Like Tyrosine Kinase 3 ,Leukemia, Myeloid ,Tandem Repeat Sequences ,030220 oncology & carcinogenesis ,Tyrosine Kinase 3 ,embryonic structures ,Flt3 mutation ,Acute Disease ,Mutation ,Female ,business ,Tyrosine kinase ,030215 immunology ,medicine.drug - Abstract
Two distinct forms of FMS-like tyrosine kinase 3 (FLT3) mutations, internal tandem duplication (ITD) in the juxtamembrane domain and point mutation within the activation loop of the tyrosine kinase domain (TKD), have been identified in considerable number of patients with AML. This study was aimed to analyze the impacts of these mutations on clinical outcomes, and assess the efficacy of different therapeutic regimens (allo-HSCT, sorafenib, or conventional chemotherapy) for AML patients with FLT3 mutations after the standard induction therapy.We analyzed DNA samples from 158 consecutive de novo AML patients (18-60 years, excluding APL) with FLT3 mutations between July 2010 and October 2015.We found that AML patients with FLT3-TKD mutations have more favorable clinical outcomes than those with FLT3-ITD mutations. We also found that allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients (p 0.001, p = 0.071). However, compared with the clinical outcomes in non-primary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients. Further study on a large scale is still recommended.FLT3-TKD-mutated AML patients have more favorable clinical outcomes than those with FLT3-ITD mutations. Allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients. Compared with the clinical outcomes in non-primary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients.
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- 2017
28. Characterization of Killer cell immunoglobulin-like receptor (KIR) genotypes and haplotypes in ChineseHanpopulation
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Xiaoni Yuan, Xiebing Bao, Lingjie Li, Jun He, Jing Zhang, Miao Wang, Chao Xu, Huifeng Zhou, Xiao Wu, Lei Yang, and Depei Wu
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Genetics ,Linkage disequilibrium ,education.field_of_study ,Immunology ,Population ,Killer-cell immunoglobulin-like receptor ,Haplotype ,General Medicine ,Biology ,Balancing selection ,Biochemistry ,Genotype ,Immunology and Allergy ,education ,Allele frequency ,Genotyping - Abstract
We performed Killer cell immunoglobulin-like receptor (KIR) genotyping on 1271 individuals of Chinese Han origin including 102 families and 965 unrelated individuals. The families (with one child and both parents) were subjected for haplotype analysis. Forty-one different genotypes were identified. The frequencies of the KIR genotypes found in the family panel were confirmed by those found in the unrelated panel. The family study showed segregation of one A haplotype and at least 15 unique B haplotypes. The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.05%, 6.62%, and 4.90%, respectively. On the basis of the combination of KIR genes, six centromeric and seven telomeric gene motifs have been identified. Motif cB02 was the most frequent haplotype B specific centromeric segment while tB01 was the most frequent haplotype B specific telomeric segment. The distinct distribution of KIR haplotypes in each population may reflect the history of directional and balancing selection of different races. The gene combinations of group A and B1/B2/B3 haplotype were the most frequent genotypes named as Bx1, Bx2, and Bx3, present at a frequency of 13.72%, 7.35%, and 4.41% in the family panel, and at a frequency of 15.86%, 10.15%, and 5.80% in the unrelated panel, respectively. Overall, this study showed the diversity of KIR haplotypes and genotypes in Chinese Han population and developed a criterion for distinguish KIR haplotypes/genotypes for the population. KIR genotyping and haplotype analysis should be useful for selection of the most optimum donor grafts with favorable KIR gene content for transplants.
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- 2013
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29. Risk factors of clinically refractory CMV reactivation following allogeneic HSCT: a single-center study in China
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Aining Sun, Depei Wu, Huiying Qiu, Feng Chen, Xiaohui Hu, S L Xue, Suning Chen, Xiebing Bao, Q Zhu, Yao-Hua Song, Yong Xu, Xiao Ma, and Zi-Ling Zhu
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0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,China ,Transplantation Conditioning ,Adolescent ,Cytomegalovirus ,Single Center ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Refractory ,immune system diseases ,Risk Factors ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Young adult ,Child ,Retrospective Studies ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Hematology ,Middle Aged ,medicine.disease ,Cmv reactivation ,Prognosis ,surgical procedures, operative ,030104 developmental biology ,Graft-versus-host disease ,Treatment Outcome ,Allogeneic hsct ,Child, Preschool ,Cytomegalovirus Infections ,Female ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
Risk factors of clinically refractory CMV reactivation following allogeneic HSCT: a single-center study in China
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- 2016
30. Decreased Expression of PPARγ mRNA in Patients Correlates with aGVHD after Allo-HSCT
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Jia Chen, Yuhan Ji, Jubin Zhang, Xiaojin Wu, Xiebing Bao, Shoubao Ma, Shuangzhu Liu, and Depei Wu
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chemistry.chemical_classification ,integumentary system ,medicine.medical_treatment ,Immunology ,GATA3 ,Peroxisome proliferator-activated receptor ,FOXP3 ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biology ,medicine.disease ,Biochemistry ,Peripheral blood mononuclear cell ,surgical procedures, operative ,Graft-versus-host disease ,chemistry ,immune system diseases ,RAR-related orphan receptor gamma ,hemic and lymphatic diseases ,medicine ,Receptor - Abstract
Background and objective: Peroxisome proliferator-activated receptor (PPAR)-gamma(γ) is a member of superfamily of nuclear hormone receptors and involved in the lipids metabolism, adipocyte differentiation, atherosclerosis and anti-inflammation. The role of PPARγ in acute graft versus host disease (aGVHD ) remains unclear. In this study, we aimed to investigate the role of PPARγ during aGVHD after allogenic hematopoietic stem cell transplantation (allo-HSCT ). Methods: 50 patients undering allo-HSCT and 20 healthy controls were enrolled in study. Peripheral blood (PB) of patients 30 days, 60 days, and 90 days were collected after allo-HSCT. We also collected PB samples at aGVHD onset and after aGVHD remission. Peripheral blood mononuclear cells (PBMCs) were isolated for real-time PCR to detect the mRNA expression of PPARγ, IFNγ, IL4, T-bet, GATA3, Foxp3, RORγt . Results: Expression of PPARγmRNA in healthy controls were significant lower than that in patients after allo-HSCT(P Conclusion: Our findings suggest that low expression of PPARγ is associated with aGVHD occurrence. PPARγ may be a useful indicator to predict aGVHD and follow-up. Disclosures No relevant conflicts of interest to declare.
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- 2016
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31. Superiority of Outcome for Patients with Late-Onset EBV Viremia Post Allogeneic Stem Cell Transplantation: A Chinese Multicenter Survey
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Feng Chen, Aining Sun, Xiebing Bao, Chunmei Ye, Yang Xu, Jing Xu, Jia Chen, Ying Wang, Xiaoli Li, Zi-Ling Zhu, and Wu Depei
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Ganciclovir ,Oncology ,Foscarnet ,medicine.medical_specialty ,business.industry ,Immunology ,Viremia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Valaciclovir ,Transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Cumulative incidence ,Rituximab ,business ,Viral load ,medicine.drug - Abstract
Introduction EBV reactivation and associated diseases have been well recognized as one of the life threatening complications after SCT, which leads to the establishment of prophylactic and preemptive treatment for EBV viremia. However since then, few epidemic data was shown in SCT recipients, especially in China. Patients and Methods An observational data base study was conducted in patients with hematological disorders who received allo-SCT from Jun 2011 through Jun 2014. EBV-negative status was confirmed before transplant for both donors and recipients. EBV-DNA was screened weekly until Day 100 post SCT by qPCR, and then every 2-4 weeks until 1 year. Additional tests were carried out when clinically indicated. All patients received ganciclovir during conditioning regimen, and then switched to acyclovir or valaciclovir after stem cell infusion until 1 year post SCT. Ganciclovir and/or foscarnet were used when DNAemia developed, as well as rituximab for high risk patients such as high viral load or persistent DNAemia. Results This study recruited 892 evaluable cases, including 91 cases of benign diseases and 801 cases of malignancies. Until Jun 2015, EBV-DNA was detected in 178 cases with a median duration of 55 days (16-990days) post SCT, and the long-term cumulative incidence of DNAemia was 22.8¡À1.6%(Fig 1A). Log-rank test showed the onset of EBV-DNAemia had impact on neither OS nor NRM. However, For patients with late-onset EBV viremia (later than 100 days post-SCT), superiority of 3 year-OS (75.6¡À7.9% vs 65.2¡À1.8%, P=0.013) and 3 year-NRM (19.2¡À8.0% vs 25.4¡À1.7%, P=0.028) were observed(Fig 1B and Fig 1C). Furthermore, late-onset of EBV viremia was confirmed as independent protective factor for both OS£¨RR 0.466 [95%CI 0.253-0.859], P=0.014) and NRM (RR 2.271 [95%CI 1.056-4.882], P=0.036) in multivariate analysis. Cox model analysis revealed that the haploidentical donor£¨RR 4.745 [95%CI 1.624-13.866], P=0.004) and the use of ATG/ALG were independent risk factors for late-onset of EBV viremia, as well as the graft of bone marrow (RR 2.188 [95%CI 0.991-4.835], P=0.053) with a marginal significance(Figure 2). Conclusion This work showed the cumulative incidence of EBV viremia after allogeneic SCT was around 22.8% based on virus prophylaxis. As shown in multivariate analysis, late-onset of EBV viremia had independent impact on OS and NRM. Haploidentical donors, the use of ATG/ALG and graft type were independent risk factors for late-onset EBV viremia.. This work was funded by grants of Jiangsu Provincial Special Program of Medical Science (BL2012005), Jiangsu Province¡¯s Key Medical Center (ZX201102) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Figure 1. A. Cumulative incidence of EBV DNAemia; B. Comparison of OS between early-onset and late-onset of EBV viremia; C. Comparison of NRM between early-onset and late-onset of EBV viremia; Figure 1. A. Cumulative incidence of EBV DNAemia; B. Comparison of OS between early-onset and late-onset of EBV viremia; C. Comparison of NRM between early-onset and late-onset of EBV viremia; Figure 2. Independent risk factors for late-onset of EBV viremia: A. the impact of donor types; B. the impact of conditioning regimens with and without ATG/ALG; C. the impact of graft types. Figure 2. Independent risk factors for late-onset of EBV viremia: A. the impact of donor types; B. the impact of conditioning regimens with and without ATG/ALG; C. the impact of graft types. Disclosures No relevant conflicts of interest to declare.
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- 2015
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