441 results on '"Kai Yan"'
Search Results
2. Donor activating killer cell immunoglobulin‐like receptors genes correlated with Epstein–Barr virus reactivation after haploidentical haematopoietic stem cell transplantation
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Ze-Ying Fan, Xiao-Su Zhao, Lan-Ping Xu, Ying-Jun Chang, Xing-Xing Yu, Xiao-Jun Huang, Xue-Fei Liu, Xiang Wang, Kai-Yan Liu, Qian-Nan Shang, Xiang-Yu Zhao, Yu Wang, Xiao-Hui Zhang, Xun-Hong Cao, and Ming-Rui Huo
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Adult ,Male ,Epstein-Barr Virus Infections ,Transplantation Conditioning ,Adolescent ,Cell ,medicine.disease_cause ,Virus ,Young Adult ,Receptors, KIR ,hemic and lymphatic diseases ,medicine ,Humans ,Child ,Receptor ,biology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Epstein–Barr virus ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,Child, Preschool ,Immunology ,biology.protein ,Female ,Antibody ,Stem cell ,business - Abstract
Natural killer (NK) cells exert anti-viral effects after haematopoietic stem cell transplantation (HSCT). The balance between inhibition and activation of NK cells determined by the inherited repertoire of killer cell immunoglobulin-like receptors (KIR) genes may influence Epstein-Barr virus (EBV) reactivation after transplantation. To evaluate the relative contributions of KIR genotypes to EBV reactivation, we prospectively enrolled 300 patients with malignant haematological disease who were suitable for haploidentical HSCT. Univariate analysis showed that donors with KIR2DS1, KIR2DS3 or KIR3DS1 genes were associated with an increased risk of EBV reactivation [hazard ratio (HR) 1·86, 95% confidence interval (CI) 1·19-2·9, P = 0·0067; HR 1·78, 95% CI 1·07-2·97, P = 0·027; HR 1·86, 95% CI 1·19-2·91, P = 0·0065 respectively]. Multivariate analysis revealed that the presence of KIR2DS1, KIR2DS3 or KIR3DS1 genes was associated with increased EBV reactivation after HSCT. This effect was more evident in the absence of the cognate ligands for the corresponding activating receptors. Our present data firstly showed that donors with activating KIR genes, specifically activating KIR2DS1, KIR2DS3 and KIR3DS1, had an increased risk of EBV reactivation. Precaution for patients whose donors carry activating genes will help prevent EBV reactivation and improve patient prognosis after HSCT.
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- 2021
3. Clinical risk factors and prognostic model for idiopathic inflammatory demyelinating diseases after haploidentical hematopoietic stem cell transplantation in patients with hematological malignancies
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Ye-Jun Wu, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang, Kai-Yan Liu, and Rui-Xin Deng
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,Graft vs Host Disease ,Disease ,Hematopoietic stem cell transplantation ,Young Adult ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Child ,Aged ,Retrospective Studies ,Receiver operating characteristic ,business.industry ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Transplantation ,surgical procedures, operative ,Child, Preschool ,Hematologic Neoplasms ,Transplantation, Haploidentical ,Cohort ,Female ,business ,Demyelinating Diseases - Abstract
Idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system (CNS) are rare but serious neurological complications of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). However, the risk factors and a method to predict the prognosis of post-transplantation CNS IIDDs are not available. This retrospective study first reviewed data from 4532 patients who received haplo-HSCT during 2008-2019 in our center, and 184 patients (4.1%) with IIDDs after haplo-HSCT were identified. Grades II to IV acute graft-versus-host disease (aGVHD) (p < 0.001) and chronic GVHD (cGVHD) (p = 0.009) were identified as risk factors for developing IIDDs after haplo-HSCT. We then divided the 184 IIDD patients into a derivation cohort and validation cohort due to transplantation time to develop and validate a model for predicting the prognosis of IIDDs. In the multivariate analysis of the derivation cohort, four candidate predictors were entered into the final prognostic model: cytomegalovirus (CMV) infection, Epstein-Barr virus (EBV) infection, IgG synthesis (IgG-syn) and spinal cord lesions. The prognostic model had an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.803-0.925) in the internal validation cohort and 0.871 (95% CI: 0.806-0.931) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. Decision curve analysis indicated that IIDD patients could benefit from the clinical application of the prognostic model. The identification of IIDD patients after allo-HSCT who have a poor prognosis might allow timely treatment and improve patient survival and outcomes.
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- 2021
4. The association between hypertension and nonalcoholic fatty liver disease (NAFLD): literature evidence and systems biology analysis
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Tian Xu, Chongyang Ma, Qiuyun Zhang, Fafeng Cheng, Yuqiong Du, Lianyin Gao, Zisong Wang, Jiayang Sai, and Kai Yan
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0301 basic medicine ,Male ,Proteome ,Systems biology ,Bioengineering ,Bioinformatics ,Applied Microbiology and Biotechnology ,digestive system ,Aldehyde Dehydrogenase 1 Family ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,NAFLD ,Hyperlipidemia ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Humans ,Protein Interaction Maps ,KEGG ,Depression (differential diagnoses) ,ALDH1A1 ,Reverse causality ,business.industry ,Systems Biology ,nutritional and metabolic diseases ,Retinal Dehydrogenase ,General Medicine ,medicine.disease ,Comorbidity ,digestive system diseases ,030104 developmental biology ,Clinical research ,Hypertension ,030211 gastroenterology & hepatology ,protein-protein interaction network ,business ,Transcriptome ,TP248.13-248.65 ,Biotechnology ,Research Article ,Research Paper - Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue as its progression increases risks of multisystem morbidity and mortality. Recent evidence indicates a more complex relationship between hypertension and NAFLD than previously thought. In this study, a comprehensive literature search was used to gather information supporting the comorbidity phenomenon of hypertension and NAFLD. Then, systems biology approach was applied to identify the potential genes and mechanisms simultaneously associated with hypertension and NAFLD. With the help of protein-protein interaction network-based algorithm, we found that the distance between hypertension and NAFLD was much less than random ones. Sixty-four shared genes of hypertension and NAFLD modules were identified as core genes. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis indicated that some inflammatory, metabolic and endocrine signals were related to the potential biological functions of core genes. More importantly, drugs used to treat cardiovascular diseases, hypertension, hyperlipidemia, inflammatory diseases and depression could be potential therapeutics against hypertension-NAFLD co-occurrence. After analyzing public OMICs data, ALDH1A1 was identified as a potential therapeutic target, without being affected by reverse causality. These findings give a clue for the potential mechanisms of comorbidity of hypertension and NAFLD and highlight the multiple target-therapeutic strategy of NAFLD for future clinical research., Graphical Abstract
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- 2021
5. Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation
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Chen-Hua Yan, Xiao-Dong Mo, Yi-Fei Cheng, Xiao-Su Zhao, Xiao-Jun Huang, Yu Wang, Yu-Hong Chen, Huan Chen, Xiao-Hui Zhang, Wei Han, Ya-Zhen Qin, Juan-Juan Wen, Lan-Ping Xu, Dao-Xing Deng, Feng-Rong Wang, Kai-Yan Liu, and Jing-Zhi Wang
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Male ,Oncology ,Cancer Research ,Neoplasm, Residual ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Hematopoietic stem cell transplantation ,0302 clinical medicine ,Bone Marrow ,hemic and lymphatic diseases ,Medicine ,Cumulative incidence ,Relapse ,Child ,Pediatric ,Hematology ,Incidence ,Hematopoietic Stem Cell Transplantation ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Leukemia, Myeloid, Acute ,Child, Preschool ,030220 oncology & carcinogenesis ,Allogeneic hematopoietic stem cell transplantation ,Female ,Research Article ,medicine.medical_specialty ,Adolescent ,Risk Assessment ,lcsh:RC254-282 ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,Genetics ,Humans ,Transplantation, Homologous ,Risk factor ,WT1 Proteins ,Acute myeloid leukemia ,business.industry ,Infant ,Adult Acute Myeloid Leukemia ,Wilms' tumor ,medicine.disease ,Wilms’ tumor gene 1 ,Minimal residual disease ,Confidence interval ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
Background Sequential monitoring of Wilms’ tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children. Methods Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan–Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM. Results Of the 151 consecutive patients included, the median age was 10 years (range, 1–17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25–6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies. Conclusions Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.
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- 2021
6. HCMV modulates c‐Mpl/IEX‐1 pathway‐mediated megakaryo/thrombopoiesis via PDGFRα and αvβ3 receptors after allo‐HSCT
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Yu-Hong Chen, Kai-Yan Liu, Gao-Chao Zhang, Ying-Jun Chang, Xiao-Lu Zhu, Xiao-Hui Zhang, Xiao Liu, Lan-Ping Xu, Hai-Xia Fu, Yun He, Wei Han, Fei-Er Feng, Feng-Qi Liu, Yu Wang, Xiao-Jun Huang, and Jing-Zhi Wang
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Male ,0301 basic medicine ,Human cytomegalovirus ,Receptor, Platelet-Derived Growth Factor alpha ,Physiology ,viruses ,Clinical Biochemistry ,Cytomegalovirus ,Apoptosis ,0302 clinical medicine ,Megakaryocyte ,Risk Factors ,Platelet ,Thrombopoiesis ,Child ,Receptor ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Middle Aged ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Female ,Megakaryocytes ,Receptors, Thrombopoietin ,Signal Transduction ,Adult ,Adolescent ,Down-Regulation ,Young Adult ,03 medical and health sciences ,In vivo ,medicine ,Humans ,Transplantation, Homologous ,Megakaryopoiesis ,Ploidies ,business.industry ,Membrane Proteins ,Cell Biology ,Integrin alphaVbeta3 ,medicine.disease ,Toll-Like Receptor 2 ,030104 developmental biology ,Multivariate Analysis ,Immunology ,Apoptosis Regulatory Proteins ,business - Abstract
Thrombocytopenia is a common complication of human cytomegalovirus (HCMV) infection in immunocompromised hosts, which contributes to poor prognosis even in patients receiving antiviral treatment. Here, we investigated the megakaryo/thrombopoiesis process, including the involvement of the c-Mpl/IEX-1 pathway, after HCMV infection, identified receptors mediating the interaction between megakaryocytes (MKs) and HCMV, and explored novel therapeutic targets. Our data shows that HCMV directly infects megakaryocytes in patients with HCMV DNAemia and influences megakaryopoiesis via the c-Mpl/IEX-1 pathway throughout megakaryocyte maturation, apoptosis, and platelet generation in vivo and in vitro. After treatment with inhibitors of PDGFRα and αvβ3, the HCMV infection rate in MKs was significantly reduced, suggesting that IMC-3G3 and anti-αvβ3 are potential therapeutic alternatives for viral infection. In summary, our study proposes a possible mechanism and potential treatments for thrombocytopenia caused by HCMV infection and other viral diseases associated with abnormal hemostasis.
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- 2021
7. Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
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Yunchao Su, Yu-Qian Sun, Jianping Zhang, Xiao-Hui Zhang, Yao Chen, Junfang Yang, Xiao-Dong Mo, Xian Zhang, Dan Song, Kai-Yan Liu, Min Zhang, Xiao-Jun Huang, Huan Chen, Gailing Zhang, Wenqian Li, Chen-Hua Yan, Yanze Shi, Yu Wang, Li Xu, Yi-Fei Cheng, Lan-Ping Xu, Yu-Hong Chen, Peihua Lu, and Wei Han
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Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Long term follow up ,T-Lymphocytes ,Lymphoblastic Leukemia ,medicine.medical_treatment ,Immunology ,Receptors, Antigen, T-Cell ,Hematopoietic stem cell transplantation ,Immunotherapy, Adoptive ,Gastroenterology ,CD19 ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Genetics (clinical) ,Cell Proliferation ,B-Lymphocytes ,Transplantation ,biology ,business.industry ,Interleukins ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Complete remission ,Cell Biology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prostate-Specific Antigen ,Chimeric antigen receptor ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Relapsed refractory ,biology.protein ,Interleukin-2 ,Female ,Chimeric Antigen Receptor T-Cell Therapy ,business - Abstract
Background aims The efficacy of CD19-targeted chimeric antigen receptor T (CAR T) cells for treatment of relapsed B-cell malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the long-term outcomes of these patients remain inconclusive. Methods The authors focused on the survival of 35 patients with B-cell acute lymphoblastic leukemia who relapsed after allo-HSCT and received CAR T cells. Results Of the 34 eligible patients, 30 achieved minimal residual disease-negative complete remission (CR), with a total CR rate of 85.7% (79.8–91.6%). There were 14 patients who received various forms of additional therapy after achieving CR. After a median follow-up of 20.7 months, it was noted that 17 patients had relapsed at a median of 4.5 months (2–34 months). The cumulative recurrence rate (RR) at 18 months was 68.3% (57.6–79.0%). Additional treatment did not reduce the RR but seemed to delay the time to relapse (mean: 5.9 months vs 13.1 months; P = 0.046). Patients with a lower tumor burden (≤10%) had a lower RR (25.0% vs 78.6% at 12 months; P = 0.006). The overall survival (OS) rate for the CR patients was 30.0% (20.3–29.7%) at 18 months, with a median OS of 12.7 months. Conclusions The authors’ study indicated that for patients who relapsed after HSCT, although a high CR rate was achieved after CAR T therapy, the long-term efficacy was unsatisfactory. It is necessary to optimize additional treatment, including a second HSCT, to further improve long-term efficacy after CAR T infusion.
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- 2020
8. Preemptive interferon-α treatment could protect against relapse and improve long-term survival of ALL patients after allo-HSCT
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Xue-Yi Luo, Xiao-Hui Zhang, Feng-Rong Wang, Huan Chen, Wei Han, Chen-Hua Yan, Sining Liu, Yu Wang, Xiao-Jun Huang, Kai-Yan Liu, Lan-Ping Xu, Yu-Hong Chen, Jing-Zhi Wang, and Xiao-Dong Mo
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,lcsh:Medicine ,Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Interferon ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Leukaemia ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Young adult ,Child ,lcsh:Science ,Multidisciplinary ,Acute lymphocytic leukaemia ,business.industry ,lcsh:R ,Hematopoietic Stem Cell Transplantation ,Interferon-alpha ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Minimal residual disease ,Transplantation ,Clinical trial ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,lcsh:Q ,business ,030215 immunology ,medicine.drug - Abstract
Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).
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- 2020
9. Immune profiling identifies CD8
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Zhen, Chen, Meng-Li, Guo, Ya-Yi, Li, Kai, Yan, Liang, Li, Fei, Shen, Haixia, Guan, Qing-Zhi, Liu, Bo, Xu, and Zhe-Xiong, Lian
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Male ,Thyroid Cancer, Papillary ,Programmed Cell Death 1 Receptor ,Tumor Microenvironment ,Humans ,Female ,Thyroid Neoplasms ,CD8-Positive T-Lymphocytes ,Prognosis ,T-Lymphocytes, Regulatory - Abstract
Thyroid tissue has a special immune microenvironment that is not well characterized. Whether immune cells have a prognostic value in the recurrence of papillary thyroid cancer (PTC) needs further investigation.Multinodular non-toxic goiter (MNG) was taken as normal tissue for the difficulty in obtaining completely normal thyroid tissue (normal thyroid function, no thyroiditis, and no nodules). We compared the composition of mononuclear cells (MNCs) in peripheral blood and thyroid tissues from MNG and PTC patients by high-dimensional flow cytometry profiling and verified the results by multiplex immunohistochemistry. The recurrence rates of PTC patients with different CD8We observed that the immune cell composition of MNG was different from that in peripheral blood. Thyroid tissue contains higher percentages of T cells and NK cells. Moreover, the percentages of memory T cells and Treg cells were higher in thyroid than in peripheral blood and increased in PTC tumors. We further focused on the antitumoral CD8The immune microenvironment in MNG tissue is distinct from that in peripheral blood and paratumor tissue. More memory CD8
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- 2022
10. Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation
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Xing-Xing Yu, Qian-Nan Shang, Xue-Fei Liu, Mei He, Xu-Ying Pei, Xiao-Dong Mo, Meng Lv, Ting-Ting Han, Ming-Rui Huo, Xiao-Su Zhao, Ying-Jun Chang, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiang-Yu Zhao, and Xiao-Jun Huang
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Adult ,Graft Rejection ,Male ,Adolescent ,DNA Mutational Analysis ,Cytomegalovirus ,Cell Line ,Mice ,Young Adult ,Animals ,Humans ,Prospective Studies ,Homozygote ,Hematopoietic Stem Cell Transplantation ,DNA ,General Medicine ,Middle Aged ,Tissue Donors ,Killer Cells, Natural ,Cytomegalovirus Infections ,Mutation ,Transplantation, Haploidentical ,Female ,Virus Activation ,NK Cell Lectin-Like Receptor Subfamily C ,Follow-Up Studies - Abstract
CMV infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several investigators have reported that adaptive NKG2C+ NK cells persistently expand during CMV reactivation. In our study, 2 cohorts were enrolled to explore the relationships among the NKG2C genotype, NKG2C+ NK cell reconstitution, and CMV infection. Multivariate analysis showed that donor NKG2C gene deletion was an independent prognostic factor for CMV reactivation and refractory CMV reactivation. Furthermore, adaptive NKG2C+ NK cells' quantitative and qualitative reconstitution, along with their anti-CMV function after transplantation, was significantly lower in patients grafted with NKG2Cwt/del donor cells than in those grafted with NKG2Cwt/wt donor cells. At day 30 after transplantation, quantitative reconstitution of NKG2C+ NK cells was significantly lower in patients with treatment-refractory CMV reactivation than in patients without CMV reactivation and those with nonrefractory CMV reactivation. In humanized CMV-infected mice, we found that, compared with those from NKG2Cwt/del donors, adaptive NKG2C+ NK cells from NKG2Cwt/wt donors induced earlier and stronger expansion of NKG2C+ NK cells as well as earlier and stronger CMV clearance in vivo. In conclusion, donor NKG2C homozygosity contributes to CMV clearance by promoting the quantitative and qualitative reconstruction of adaptive NKG2C+ NK cells after haploidentical allo-HSCT.
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- 2022
11. Preemptive Interferon-α Therapy Could Protect Against Relapse and Improve Survival of Acute Myeloid Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation: Long-Term Results of Two Registry Studies
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Meng-Zhu Shen, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Xiao-Su Zhao, Ya-Zhen Qin, Ying-Jun Chang, Kai-Yan Liu, Xiao-Jun Huang, and Xiao-Dong Mo
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Adult ,Male ,Neoplasm, Residual ,Transplantation Conditioning ,Adolescent ,Injections, Subcutaneous ,Immunology ,Graft vs Host Disease ,Interferon alpha-2 ,acute myeloid leukemia ,Disease-Free Survival ,Young Adult ,preemptive ,interferon-α ,Recurrence ,Secondary Prevention ,Humans ,Immunologic Factors ,Transplantation, Homologous ,Immunology and Allergy ,Prospective Studies ,Registries ,Child ,Aged ,Middle Aged ,RC581-607 ,Leukemia, Myeloid, Acute ,hematopoietic stem cell transplantation ,minimal residual disease ,Female ,Immunologic diseases. Allergy ,Follow-Up Studies - Abstract
For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5–30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4–20.6%) and 3.9% (95%CI, 0.0–17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2–91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4–95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5–77.0%) and 10.4% (95%CI, 3.6–17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.
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- 2022
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12. Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/Recurrent Minimal Residual Disease in First Complete Remission
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Guan-hua Hu, Yi-fei Cheng, Ying-xi Zuo, Ying-jun Chang, Pan Suo, Jun Wu, Yue-ping Jia, Ai-dong Lu, Ying-chun Li, Yu Wang, Shun-chang Jiao, Long-ji Zhang, Xiang-yu Zhao, Chen-hua Yan, Lan-ping Xu, Xiao-hui Zhang, Kai-yan Liu, Le-ping Zhang, and Xiao-jun Huang
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Male ,measurable residual disease ,Neoplasm, Residual ,pediatrics ,Adolescent ,Immunology ,Remission Induction ,Infant ,chimeric antigen receptor T-cell ,RC581-607 ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Adoptive Transfer ,acute lymphocyte leukemia ,Disease-Free Survival ,Survival Rate ,hemic and lymphatic diseases ,Child, Preschool ,Immunology and Allergy ,Humans ,pre-empty therapy ,Female ,Prospective Studies ,Immunologic diseases. Allergy ,Child ,Original Research - Abstract
BackgroundThe presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear.MethodsWe conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.ResultsA total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8–90.7%) vs. 68.7% (95% CI, 47.7–89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8–90.7%) vs. 28.6% (95% CI, 4.9–52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion.ConclusionsOur findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.
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- 2022
13. Comparison of different cytomegalovirus diseases following haploidentical hematopoietic stem cell transplantation
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Yuan-Yuan Zhang, Xiao-Dong Mo, Wei Han, Xiao Liu, Hai-Xia Fu, Lan-Ping Xu, Ding-Bao Chen, Xiao-Hui Zhang, Xiao-Jun Huang, Ying-Jun Chang, Hui-Xin Liu, Yu-Hong Chen, Kai-Yan Liu, Chen-Hua Yan, Xiao-Lu Zhu, Jing-Zhi Wang, Xing-Ye Meng, and Yu Wang
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,medicine.medical_treatment ,Cytomegalovirus ,Retinitis ,Hematopoietic stem cell transplantation ,medicine.disease_cause ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Child ,Retrospective Studies ,Hematology ,business.industry ,Hematopoietic Stem Cell Transplantation ,virus diseases ,General Medicine ,Middle Aged ,Allografts ,medicine.disease ,Survival Rate ,Transplantation ,Pneumonia ,Child, Preschool ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Female ,business ,Viral load ,Encephalitis ,030215 immunology - Abstract
Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.
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- 2020
14. Enriched environment improves post-stroke cognitive impairment and inhibits neuroinflammation and oxidative stress by activating Nrf2-ARE pathway
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Xiaoya Chen, Mingyue Wen, Kai Yan, Xin-Xin Zhang, Song-Bin Yang, Mei Yuan, Xia Bi, and Jichun Wu
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Male ,0301 basic medicine ,NF-E2-Related Factor 2 ,Environment ,medicine.disease_cause ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Cognitive Dysfunction ,Cognitive impairment ,Neuroinflammation ,Ischemic Stroke ,Environmental enrichment ,business.industry ,General Neuroscience ,Stroke Rehabilitation ,Infarction, Middle Cerebral Artery ,General Medicine ,Antioxidant Response Elements ,Rats ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Neuroinflammatory Diseases ,Post stroke ,business ,Neuroscience ,030217 neurology & neurosurgery ,Oxidative stress ,Signal Transduction - Abstract
Neuroinflammation and oxidative stress are major mechanisms of post-stroke cognitive impairment (PSCI) neural injury and decreased spatial and memory capacity. Enriched environment (EE) is an effective method to improve cognitive dysfunction. However, the regulation by EE of neuroinflammation, oxidative stress and associated mechanisms in animal models remains unclear.In this study, a rat PSCI model was established by middle cerebral artery occlusion (MCAO). Rats were randomly divided into the control group, standard environment (SE) group and EE group for 28 days. A Morris water-maze test was used to measure cognitive function at 7, 14 and 28 days after MCAO. Rats were sacrificed on the 28th day. Quantitative PCR, immunohistochemistry and ELISA were respectively used to detect mRNA expression of NF-E2-related factor 2 (Nrf2) and Nrf2 response genes, the expression of IL-1β and levels of proinflammatory cytokines in the hippocampus.EE improved mNSS scores and cognitive ability in PSCI rats. EE increased mRNA expression of the Nrf2 and Nrf2 response genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). EE significantly decreased the level of malondialdehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), in the hippocampus of PSCI rats. EE reduced the number of IL-1β positive cells in the hippocampus, and IL-1β levels in the hippocampus and serum. EE increased GFAP-positive astrocytes in the hippocampus, and BDNF levels in the hippocampus and serum.EE can improve cognitive function in PSCI rats by inhibiting neuroinflammation and oxidative stress.
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- 2020
15. Prognostic factors and long‐term follow‐up of basiliximab for steroid‐refractory acute <scp>graft‐versus‐host disease</scp> : Updated experience from a large‐scale study
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Yu-Hong Chen, Chen-Hua Yan, Huan Chen, Wei Han, Xiao-Dong Mo, Sining Liu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang, Feng-Rong Wang, Lan-Ping Xu, Yu Wang, and Jing-Zhi Wang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multivariate analysis ,Long term follow up ,Basiliximab ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Internal medicine ,Acute graft versus host disease ,medicine ,Humans ,Cumulative incidence ,Retrospective Studies ,Framingham Risk Score ,business.industry ,Hematology ,Prognosis ,Survival Analysis ,Treatment Outcome ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,Steroid refractory ,business ,Immunosuppressive Agents ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Acute graft-vs-host disease (aGVHD) is one of the most important causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly for those with steroid-refractory (SR)-aGVHD. We aimed to identify the prognostic factors and long-term clinical outcomes of basiliximab treatment for SR-aGVHD. Basiliximab was administered on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II, or patients showed no response after four doses. Out of 1498 patients receiving allo-HSCT, 230 patients with SR-aGVHD were enrolled. Grade III to IV aGVHD before basiliximab treatment significantly and independently predicted a poorer response to basiliximab in multivariate analysis. And, the cumulative incidence of overall response at 14 days, 28 days, and 56 days after treatment was 41.4% vs 23.1% (P = .023), 70.2% vs 43.6% (P = .002), and 80.1% vs 66.7% (P = .013), respectively. This was for those with grade II and grade III to IV aGVHD. Patients receiving more than four doses of basiliximab had higher rates of infections. The 4-year cumulative incidence of total and severe chronic GVHD after basiliximab treatment was 44.8% (95% CI 38.3%-51.3%) and 2.2% (95% CI 0.3%-4.1%), respectively. The 4-year cumulative incidence of relapse, non-relapse mortality, disease-free survival, and overall survival after basiliximab treatment was 11.3% (95% CI 7.2%-15.4%), 30.0% (95% CI 24.1%-35.9%), 58.7% (95% CI 52.3%-65.1%), and 61.7% (95% CI 55.4%-68.0%), respectively. Comorbidities before allo-HSCT and refined Minnesota aGVHD risk score at diagnosis had significant influences on long-term survival. Thus, basiliximab was a safe and effective treatment for patients with SR-aGVHD.
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- 2020
16. Osteoclast stimulatory transmembrane protein ( OC‐STAMP ) is a promising molecular prognostic indicator for multiple myeloma
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Jin Lu, Ying-Jun Chang, Yue-Yun Lai, Yang Liu, Jin-Lan Li, Zi-Long Wang, Kai-Yan Liu, Guo-Rui Ruan, Lei Wen, Li-Xin Wu, Yan-Rong Liu, Ya-Lan Zhou, Xiao-Jun Huang, Qiu-Yu Sun, and Hong-Xia Shi
- Subjects
Adult ,Male ,Biopsy ,Peripheral blood mononuclear cell ,Translocation, Genetic ,Immunophenotyping ,Flow cytometry ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Bone Marrow ,Cell Line, Tumor ,Biomarkers, Tumor ,Humans ,Medicine ,RNA, Messenger ,Gene ,Osteoclast stimulatory transmembrane protein ,Multiple myeloma ,Aged ,Neoplasm Staging ,Oc stamp ,Aged, 80 and over ,Chromosome Aberrations ,medicine.diagnostic_test ,business.industry ,Membrane Proteins ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Minimal residual disease ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Female ,Bone marrow ,Tumor Suppressor Protein p53 ,Multiple Myeloma ,business ,030215 immunology - Abstract
BACKGROUND Currently, the prognostic stratification and therapeutic evaluation systems for multiple myeloma (MM) lack specific molecular indicators. OC-STAMP is a new gene and is also highly expressed in MM. METHODS A total of 160 MM patients have been investigated with both quantitative reverse transcription PCR (RT-qPCR), flow cytometry (FCM) and cytogenetic FISH on the same mononuclear cells isolated from bone marrow specimens. RESULTS We found that OC-STAMP mRNA levels were significantly higher in newly diagnosed cases of MM than in healthy donors (median, 0.52% vs. 0.02%, P
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- 2020
17. Detection of measurable residual disease may better predict outcomes than mutations based on next‐generation sequencing in acute myeloid leukaemia with biallelic mutations of CEBPA
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Xiaohong Liu, Hao Jiang, Lizhong Gong, Ying Wu, Yu Wang, Jing Wang, Guo-Rui Ruan, Lan-Ping Xu, Xiao-Hui Zhang, Hong-Xia Shi, Jinsong Jia, Yue-Yun Lai, Lu Runqing, Sheng-Ye Lu, Xiao-Su Zhao, Kai-Yan Liu, Xiao-Jun Huang, Chen-Hua Yan, and Qian Jiang
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Prognostic factor ,Neoplasm, Residual ,Adolescent ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Disease ,Risk Assessment ,DNA sequencing ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,CEBPA ,medicine ,Humans ,Anthracyclines ,Cumulative incidence ,Alleles ,Aged ,Chemotherapy ,business.industry ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,High-Throughput Nucleotide Sequencing ,Hematology ,Middle Aged ,Allografts ,Prognosis ,Combined Modality Therapy ,Progression-Free Survival ,MRD Negative ,Neoplasm Proteins ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,CCAAT-Enhancer-Binding Proteins ,Female ,Myeloid leukaemia ,Idarubicin ,business ,030215 immunology - Abstract
Acute myeloid leukaemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30-50% relapse rate. This study established the value of mutations based on next-generation sequencing (NGS) and multiparameter flow cytometric measurable residual disease (MFC-MRD) detection and compared the outcomes. From 2014 to 2018, 124 newly diagnosed bi CEBPA AML patients were treated. The median age was 37·5 (16-69) years. The 3-year cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS) were 33·0%, 64·7% and 84·3%, respectively. Patients without additional mutations and with GATA2 mutations were defined as 'NGS low risk', which was the only favourable independent factor for CIR and RFS of pretreatment parameters. Patients with sustained positive MRD after two consolidation cycles and MRD negative losses at any time were defined as 'MRD high risk', which was the only poor independent factor for CIR, RFS and OS, including pretreatment and post-treatment parameters. In CR2 and non-remission patients who underwent allo-HSCT, superior OS was achieved. We conclude that NGS low risk was a favourable factor in the analysis of pretreatment parameters. MRD risk stratification was an independent prognostic factor in pretreatment and post-treatment parameters. Relapsed patients still have a favourable outcome followed by allo-HSCT.
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- 2020
18. DPEP1 expression promotes proliferation and survival of leukaemia cells and correlates with relapse in adults with common B cell acute lymphoblastic leukaemia
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Li-Xin Wu, Xiao-Hui Zhang, Hao Jiang, Jia-Min Zhang, Kai-Yan Liu, Guo-Rui Ruan, Lan-Ping Xu, Ya-Zhen Qin, Qian Jiang, Jing Zhang, Yonghuai Feng, Yu-Hong Chen, Xiao-Jun Huang, Yu Wang, Yan Xu, Yan-Rong Liu, Robert Peter Gale, and Bin Jiang
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Male ,Dipeptidases ,Mice, Nude ,GPI-Linked Proteins ,Clinical correlation ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Animals ,Humans ,Medicine ,Cumulative incidence ,B cell ,Cell Proliferation ,Metalloproteinase ,business.industry ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,B-cell acute lymphoblastic leukaemia ,Cancer research ,Female ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
Dehydropeptidase-1 (DPEP1) is a zinc-dependent metalloproteinase abnormally expressed in many cancers. However, its potential role in adults with B cell acute lymphoblastic leukaemia (ALL) is unknown. We found that in adults with common B cell ALL high DPEP1, transcript levels at diagnosis were independently associated with an increased cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS) compared with subjects with low transcript levels. We show an increased proliferation and prosurvival role of DPEP1 in B cell ALL cells via regulation of phosphCREB and p53, which may be the biological basis of the clinical correlation we report. Our data implicate DPEP1 expression in the biology of common B cell ALL in adults. We report clinical correlates and provide a potential biological basis for these correlations. If confirmed, analysing DPEP1 transcript levels at diagnosis could help predict therapy outcomes. Moreover, regulation of DPEP1 expression could be a therapy target in B cell ALL.
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- 2020
19. Early downregulation of P‐glycoprotein facilitates bacterial attachment to intestinal epithelial cells and thereby triggers barrier dysfunction in a rodent model of total parenteral nutrition
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Jun-Kai Yan, Wei Cai, Tian Zhang, and Yang Liu
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Male ,0301 basic medicine ,Blotting, Western ,Ileum ,Protein degradation ,Real-Time Polymerase Chain Reaction ,Occludin ,Biochemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Escherichia coli ,Genetics ,medicine ,Animals ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Molecular Biology ,Barrier function ,P-glycoprotein ,Tight junction ,biology ,Protein Stability ,Chemistry ,Epithelial Cells ,Matrix Metalloproteinases ,In vitro ,Rats ,Cell biology ,Intestines ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Parenteral Nutrition, Total ,Caco-2 Cells ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Intestinal barrier dysfunction is a major complication of total parenteral nutrition (TPN). Our preliminary study revealed that intestinal P-glycoprotein (P-gp) was significantly downregulated under TPN treatment followed by disruption of barrier function, and thus the significance of early downregulation of P-gp needs to be addressed. Herein, we report a pivotal role of P-gp in the development of intestinal barrier dysfunction under TPN. Functional suppression of P-gp may facilitate bacterial attachment to intestinal epithelial cells (IECs) and thereby induce degradation of tight junctions to trigger barrier dysfunction. By using a rat model of TPN, we found early downregulation of P-gp function in ileum after 3-day TPN, followed by disruption of barrier function after 7-day TPN. By using Escherichia coli (E. coli) k88 and DH5α as type strains, we found significantly increased bacterial attachment to IECs in TPN group compared to sham. By using Caco-2 cells as an IEC model in vitro, we found that functional suppression of P-gp remarkably facilitated bacterial attachment to Caco-2 cells, leading to subsequent disruption of intestinal barrier function. Of note, Occludin was significantly downregulated by bacterial attachment when P-gp was functionally suppressed. Mechanistically, changes on Occludin were attributed to enhanced protein degradation instead of suppressed protein translation. Despite the half-life of Occludin protein being unchanged by DH5α treatment alone, it was decreased by about 40% when P-gp was simultaneously suppressed. Taken together, our findings revealed that early downregulation of intestinal P-gp under TPN may be a potential therapeutic target to prevent the development of barrier dysfunction.
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- 2020
20. Multiple genetic factors affecting the pharmacokinetic and pharmacodynamic processes of tacrolimus in Chinese myasthenia gravis patients
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Xiaohua Dong, Cheng-Kai Yan, Zhaohui Luo, Xi Li, Huanyu Meng, Qiu Xu, Liqun Xu, Yi Li, Wanlin Jin, Yuyao Peng, Zhibin Li, and Huan Yang
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Adult ,Male ,Adolescent ,Genotype ,In silico ,MiRNA binding ,Single-nucleotide polymorphism ,Pharmacology ,Polymorphism, Single Nucleotide ,030226 pharmacology & pharmacy ,Tacrolimus ,Tacrolimus Binding Proteins ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Pharmacokinetics ,Myasthenia Gravis ,Cytochrome P-450 CYP3A ,Humans ,SNP ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Allele ,Child ,CYP3A5 ,Aged ,NFATC Transcription Factors ,business.industry ,General Medicine ,Middle Aged ,MicroRNAs ,Female ,business ,Immunosuppressive Agents - Abstract
Tacrolimus is a novel effective immunosuppressant for myasthenia gravis (MG) patients. However, the narrow therapeutic window, and high inter- and intrapatient variation in bioavailability largely limited its clinical application. This article intended to find the SNPs influencing clinical outcome and discover the possible mechanisms. Based on the tagSNPs genotyped by Improved Multiple Ligase Detection Reaction, Plink 1.07 was used to find the SNPs having close interaction to tacrolimus serum concentration, QMG score changes or even reasonable drug dose. Then we searched several databases to predict the possible miRNA binding rs15524 sequence. Based on the prediction, dual-luciferase reporter assay and miRNA transfection were used to discover the mechanism of how SNP rs15524 controls tacrolimus serum concentration through influencing CYP3A5 expression. In this article, we found multiple SNPs on CYP3A4, CYP3A5, FKBP1A, NFATC2 genes were predicted closely related to tacrolimus serum concentration, therapeutic effect which reflected by QMG score changes or even reasonable drug dose. After in silico miRNA selection, possible relationship between hsa-miR-500a and rs15524 was found. With the help of dual-luciferase reporter assay, wild-type rs15524 (T allele) was found having a stronger binding affinity for hsa-miR-500a. Higher expression of CYP3A5 may also led by lower hsa-miR-500a level. SNP rs15524 may control CYP3A5 expression by affecting the binding affinity between CYP3A5 3’UTR and hsa-miR-500a. Wild type (T allele) 3’UTR of CYP3A5 has stronger binding affinity to hsa-miR-500a and cause lower CYP3A5 expression and higher tacrolimus serum concentration.
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- 2020
21. Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation
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Xiang-Yu Zhao, Xiao-Jun Huang, Xing-Xing Yu, Kai-Yan Liu, Ying-Jun Chang, Zheng-Li Xu, Xiao-Su Zhao, Xiao-Hui Zhang, Yu Wang, Lan-Ping Xu, Ming-Rui Huo, and Xun-Hong Cao
- Subjects
Adult ,Male ,Adolescent ,Hematopoiesis and Stem Cells ,medicine.medical_treatment ,KIR Ligand ,chemical and pharmacologic phenomena ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,Biology ,Ligands ,Young Adult ,Receptors, KIR ,KIR2DL1 ,HLA Antigens ,Recurrence ,medicine ,Humans ,Histocompatibility Testing ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Middle Aged ,medicine.disease ,Tissue Donors ,Killer Cells, Natural ,Transplantation ,Leukemia ,Treatment Outcome ,Transplantation, Haploidentical ,Cancer research ,Female ,KIR3DL1 ,Biomarkers - Abstract
The rate and extent of natural killer (NK)–cell education after hematopoietic cell transplantation correlates with leukemia control. To study the effect of donor and host HLA on NK-cell reconstitution, single killer-cell immunoglobulin-like receptor (KIR)+ NK cells (exhibiting KIR2DL1, KIR2DL2/KIR2DL3, or KIR3DL1 as their sole receptor) were grouped into 4 groups based on the interaction between donor/host HLA and donor inhibitory KIR in 2 cohorts (n = 114 and n = 276, respectively). On days 90 to 180 after transplantation, the absolute number and responsiveness against K562 cells (CD107a or interferon-γ expression) of single-KIR+ NK cells were higher in pairs where donor and host HLA both expressed ligands for donor inhibitory KIRs than in pairs where 1 or both of the donor and recipient HLA lacked at least 1 KIR ligand. NK-cell responsiveness was tuned commensurate with the number of inhibitory receptors from the donor. When both donor and host expressed the 3 major KIR ligands (HLA-C1, HLA-C2, and HLA-Bw4), NK cells expressing 3 inhibitory receptors (KIR2DL1/2DL3/3DL1) reached the maximum responsiveness against K562 cells compared with those NK cells expressing only 1 or 2 inhibitory receptors. When donor and host HLA both expressed all ligands for donor inhibitory KIRs, patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) showed the lowest recurrence rate after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). In conclusion, this study demonstrates that when both donors and hosts present all the KIR ligands for donor KIRs, reconstituted NK cells achieve better functional education and contribute to least relapse among patients. This observation study was registered at www.clinicaltrials.gov as #NCT02978274.
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- 2019
22. Influenza A(H1N1)pdm09 Virus Infection in a Captive Giant Panda, Hong Kong
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Susanna K. P. Lau, Kai-Yan Yeong, Jordan Y. H. Fong, Paolo Martelli, Patrick C. Y. Woo, Foo-Khong Lee, Suk-Wai Hui, Kwok-Hung Chan, and Jade L. L. Teng
- Subjects
Male ,Microbiology (medical) ,Influenza A(H1N1)pdm09 Virus Infection in a Captive Giant Panda, Hong Kong ,Epidemiology ,viruses ,030231 tropical medicine ,Identity (social science) ,influenza A(H1N1)pdm09 ,lcsh:Medicine ,Hemagglutinin Glycoproteins, Influenza Virus ,Genome, Viral ,Biology ,Genome ,Virus ,Cell Line ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,respiratory infections ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Orthomyxoviridae Infections ,Animals ,giant panda ,lcsh:RC109-216 ,030212 general & internal medicine ,Phylogeny ,lcsh:R ,Dispatch ,virus diseases ,Influenza a ,Genomics ,Viral Load ,Virology ,Infectious Diseases ,Antibody response ,Hong Kong ,influenza ,Viral load ,Ursidae - Abstract
We report influenza A(H1N1)pdm09 virus infection in a captive giant panda in Hong Kong. The viral load peaked on day 1 and became undetectable on day 5, and an antibody response developed. Genome analysis showed 99.3%–99.9% nucleotide identity between the virus and influenza A(H1N1)pdm09 virus circulating in Hong Kong.
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- 2019
23. Superior survival of unmanipulated haploidentical haematopoietic stem cell transplantation compared with intensive chemotherapy as post‐remission treatment for children with very high‐risk philadelphia chromosome negative B‐cell acute lymphoblastic leukaemia in first complete remission
- Author
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Ying-Xi Zuo, Yue-Ping Jia, Xiao-Jun Huang, Yi-Fei Cheng, Xiao-Hui Zhang, Kai-Yan Liu, Yu Wang, Chen-Hua Yan, Jun Kong, Jun Wu, Le-Ping Zhang, Yu-Juan Xue, Ai-Dong Lu, Pan Suo, Yu-Hong Chen, Lan-Ping Xu, and Wei Han
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,Adolescent ,Philadelphia Chromosome Negative ,medicine.medical_treatment ,Philadelphia chromosome ,Disease-Free Survival ,Group B ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Philadelphia Chromosome ,Cumulative incidence ,Child ,Chemotherapy ,business.industry ,Remission Induction ,Therapeutic effect ,Hematopoietic Stem Cell Transplantation ,Infant ,Hematology ,medicine.disease ,Survival Rate ,Transplantation ,Haematopoiesis ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,business ,Follow-Up Studies ,030215 immunology - Abstract
We explored the prognostic factors for children with very high-risk (VHR) Philadelphia chromosome (Ph) negative B-cell acute lymphoblastic leukaemia (B-ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo-HSCT) as post-remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B-ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo-HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3-year overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow-up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long-term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative-to-positive MRD. Haplo-HSCT may be an option for children with VHR Ph-negative B-ALL in CR1, especially for patients with persistent positive or negative-to-positive MRD, and could achieve better survival than intensive chemotherapy as post-remission treatment.
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- 2019
24. Effectiveness of a multidisciplinary parent training program for children with developmental disabilities: A single-blind randomized waitlist controlled trial
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Shirley Leung, Cynthia Y. Y. Lai, Tamis W. Pin, Dustin Kai-Yan Lau, and Cynthia Leung
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Adult ,Male ,Parents ,030506 rehabilitation ,Developmental Disabilities ,education ,Gross motor skill ,Pediatrics ,law.invention ,Task (project management) ,03 medical and health sciences ,Cognition ,McNemar's test ,Randomized controlled trial ,law ,Multidisciplinary approach ,Humans ,Learning ,Single-Blind Method ,0501 psychology and cognitive sciences ,Cognitive skill ,Problem Behavior ,Holistic education ,05 social sciences ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Parent training ,Hong Kong ,Female ,0305 other medical science ,Psychology ,050104 developmental & child psychology ,Clinical psychology - Abstract
This study aimed to evaluate the effectiveness of a multidisciplinary parent training program, Promoting Holistic Development of Young Kids (Poly Kids), using a single-blind randomized waitlist controlled design. The participants included 218 parents of children with developmental disabilities (DD) (intervention group = 107 and waitlist control group = 111). The primary outcomes were child learning, expressive language, fine and gross motor skills (based on individual assessment by respective blinded professionals), and parental reports of child behavior problems. The parents in the intervention group reported significantly lower child behavior problems ( d = .34), higher child task motivation ( d = .63), and lower parenting stress post-intervention ( d = .25), while the children in the intervention group produced significantly more words post-intervention ( d = .82). McNemar test results were significant for movement out of the clinical range in child behavior problems and cognitive skills in the intervention group, but not the control group. The results provided initial evidence on the effectiveness of this train-the-trainer program in supporting families with preschool children with DD in terms of child behavior problems, expressive language, cognitive skills, task motivation, and parenting stress.
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- 2019
25. Biologic Pathways Underlying Prognostic Radiomics Phenotypes from Paired MRI and RNA Sequencing in Glioblastoma
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Qiuchang Sun, Chaofeng Liang, Zhicheng Li, Dong Liang, Xiaofei Lv, Kai Yan, Yinsheng Chen, Yuanshen Zhao, Yan Zou, and Hairong Zheng
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Oncology ,Male ,medicine.medical_specialty ,Key genes ,Radiogenomics ,Radiomics ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Retrospective Studies ,Training set ,business.industry ,Brain Neoplasms ,Sequence Analysis, RNA ,Hazard ratio ,RNA ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Prognosis ,Phenotype ,Magnetic Resonance Imaging ,Female ,business ,Glioblastoma - Abstract
Background The biologic meaning of prognostic radiomics phenotypes remains poorly understood, hampered in part by lack of multicenter reproducible evidence. Purpose To uncover the biologic meaning of individual prognostic radiomics phenotypes in glioblastomas using paired MRI and RNA sequencing data and to validate the reproducibility of the identified radiogenomics linkages externally. Materials and Methods This retrospective multicenter study included four data sets gathered between January 2015 and December 2016. From a radiomics analysis set, a 13-feature radiomics signature was built using preoperative MRI for overall survival prediction. Using a radiogenomics training set with both MRI and RNA sequencing, biologic pathways were enriched and correlated with each of the 13 radiomics phenotypes. Radiomics-correlated key genes were identified to derive a prognostic radiomics gene expression (RadGene) score. The reproducibility of identified pathways and genes was validated with an external test set and a public data set (The Cancer Genome Atlas [TCGA]). A log-rank test was performed to assess prognostic significance. Results A total of 435 patients (mean age, 55 years ± 15 [standard deviation]; 263 men) were enrolled. The radiomics signature was associated with overall survival (hazard ratio [HR], 3.68; 95% CI: 2.08, 6.52; P < .001) in the radiomics validation subset. Four types of prognostic radiomics phenotypes were correlated with distinct pathways: immune, proliferative, treatment responsive, and cellular functions (false-discovery rate < 0.10). Thirty radiomics-correlated genes were identified. The prognostic significance of the RadGene score was confirmed in an external test set (HR, 2.02; 95% CI: 1.19, 3.41; P = .01) and a TCGA test set (HR, 1.43; 95% CI: 1.001, 2.04; P = .048). The radiomics-associated pathways and key genes can be replicated in an external test set. Conclusion Individual radiomics phenotypes on MRI scans predictive of overall survival were driven by distinct key pathways involved in immune regulation, tumor proliferation, treatment responses, and cellular functions in glioblastoma, which could be reproduced externally. © RSNA, 2021 Online supplemental material is available for this article.
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- 2021
26. α-Lipoic Acid Alleviates Hepatic Lipid Deposition by Inhibiting FASN Expression via miR-3548 in Rats
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Ruqian Zhao, Xi Fang, Shihui Guo, Wenqiang Ma, Yingdong Ni, and Kai Yan
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,miRNA-3548 ,Gene Expression ,030209 endocrinology & metabolism ,Fatty Acid-Binding Proteins ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Gene expression ,medicine ,Animals ,TX341-641 ,rat ,Lipase ,Gene ,Triglycerides ,Reporter gene ,Messenger RNA ,Nutrition and Dietetics ,α-lipoic acid ,biology ,Thioctic Acid ,Nutrition. Foods and food supply ,Lipogenesis ,Lipid Metabolism ,FASN ,Rats ,Fatty Acid Synthase, Type I ,Lipoic acid ,Fatty acid synthase ,MicroRNAs ,030104 developmental biology ,Endocrinology ,hepatic lipid deposition ,chemistry ,Liver ,Dietary Supplements ,biology.protein ,Phosphorylation ,lipids (amino acids, peptides, and proteins) ,Fatty Acid Synthases ,Food Science - Abstract
Excessive liver lipid deposition is a vital risk factor for the development of many diseases. Here, we fed Sprague-Dawley rats with a control or α-lipoic acid-supplemented diet (0.2%) for 5 weeks to elucidate the effects of α-lipoic acid on preventive ability, hepatic lipid metabolism-related gene expression, and the involved regulatory mechanisms. In the current study, α-lipoic acid supplementation lowered plasma triglyceride level and hepatic triglyceride content. Reduced hepatic lipid deposition was closely associated with inhibiting fatty acid-binding protein 1 and fatty acid synthase expression, as well as increasing phosphorylated hormone-sensitive lipase expression at the protein level in α-lipoic acid-exposed rats. Hepatic miRNA sequencing revealed increased expression of miR-3548 targeting the 3′untranslated region of Fasn mRNA, and the direct regulatory link between miRNA-3548 and FASN was verified by dual-luciferase reporter assay. Taken together, α-lipoic acid lowered hepatic lipid accumulation, which involved changes in miRNA-mediated lipogenic genes.
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- 2021
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27. Monitoring of Post-Transplant MLL-PTD as Minimal Residual Disease Can Predict Relapse After Allogeneic HSCT in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome
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Xiao-Jun Huang, Xiao-Hui Zhang, Kai-Yan Liu, Ying-Jun Chang, Jun Kong, Yu Wang, Meng-Ge Gao, Xiao-Su Zhao, Chen-Hua Yan, Ya-Zhen Qin, Lan-Ping Xu, and Yu-Qian Sun
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,Oncogene Proteins, Fusion ,Disease-Free Survival ,MLL-PTD ,Text mining ,Predictive Value of Tests ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Genetics ,medicine ,Humans ,Transplantation, Homologous ,In patient ,Postoperative Period ,Relapse ,neoplasms ,RC254-282 ,Retrospective Studies ,Gene Rearrangement ,business.industry ,Research ,Minimal residual disease ,Hematopoietic Stem Cell Transplantation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Myeloid leukemia ,Histone-Lysine N-Methyltransferase ,Middle Aged ,Prognosis ,Progression-Free Survival ,Post transplant ,Tumor Burden ,Leukemia, Myeloid, Acute ,Myelodysplastic Syndromes ,Allogeneic hsct ,Allogeneic hematopoietic stem cell transplantation ,Female ,Neoplasm Recurrence, Local ,business ,Myeloid-Lymphoid Leukemia Protein ,Follow-Up Studies - Abstract
Background The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. Methods We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People’s Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. Results The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD P P P P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD Conclusions Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.
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- 2021
28. Synergistic impact of resection margin and microscopic vascular invasion for patients with HBV-related intrahepatic cholangiocarcinoma
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Lei Liang, Yechen Wu, Hai-bin Zhang, Pei-Qin Chen, Kai Yan, Yong Fu, Wen-Feng Lu, and Jian-Yong Yuan
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Adult ,Male ,medicine.medical_specialty ,Hepatitis B virus ,Gastroenterology ,Vascular invasion ,Cholangiocarcinoma ,Young Adult ,Text mining ,Internal medicine ,Recurrence free survival ,medicine ,Overall survival ,Hepatectomy ,Humans ,Neoplasm Invasiveness ,Intrahepatic Cholangiocarcinoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,Margins of Excision ,Middle Aged ,Survival Analysis ,digestive system diseases ,Vascular Neoplasms ,Bile Duct Neoplasms ,Lymphatic Metastasis ,Resection margin ,Female ,business - Abstract
The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus-related ICC were retrospectively analyzed. The different impact of the RM status (narrow,1 cm, or wide, ≥1 cm) and MVI (positive, +, or negative, -) on overall survival (OS) and recurrence-free survival (RFS) were analyzed.The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RMMVI (-), 58.0%, 36.1%, and 26.5% in narrow RMMVI (-), 51.0%, 27.0%, and 24.3% in wide RMMVI (+), and 39.0%, 20.4% and 14.3% in narrow RMMVI (+) (Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.
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- 2021
29. AMPKα1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation
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Jian Xiong Feng, Zexian Liu, Dan Xie, Chao Zhang, Jia Jia Hu, Gong Chen, Huai-Qiang Ju, Yun Xin Lu, Marcia A. Ogasawara, Ying qin Li, Yang Chen, Ying Nan Wang, Qi Zhao, Jin Ping Yun, Zhizhong Pan, Hui Chang Bi, Feng Tian, Kai Yan Liu, Ying Jin, Zhao Lei Zeng, Song Gao, Yi Ming Jiang, Scott Kopetz, Feng Wang, Jie Liu, Rui-Hua Xu, Wei Hua Jia, and Hui Sheng
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Male ,Threonine ,0301 basic medicine ,Cancer Research ,Carcinogenesis ,Colorectal cancer ,Glutathione reductase ,Apoptosis ,Kaplan-Meier Estimate ,AMP-Activated Protein Kinases ,medicine.disease_cause ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Phosphorylation ,RNA, Small Interfering ,Drug Synergism ,Middle Aged ,Cancer metabolism ,Oxaliplatin ,Survival Rate ,Glutathione Reductase ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Female ,Colorectal Neoplasms ,Oxidation-Reduction ,medicine.drug ,Cell Survival ,Biology ,Article ,03 medical and health sciences ,Stress, Physiological ,Cell Line, Tumor ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Survival rate ,Aged ,Neoplasm Staging ,Glutathione ,medicine.disease ,Xenograft Model Antitumor Assays ,030104 developmental biology ,chemistry ,Cancer research ,Reactive Oxygen Species ,Homeostasis - Abstract
Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction–oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.
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- 2019
30. Risk factors for chronic graft-versus-host disease after anti-thymocyte globulin-based haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia
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Lan-Ping Xu, Meng Lv, Xiao-Hui Zhang, Yu Wang, Feng-Rong Wang, Yu-Hong Chen, Wei Han, Chen-Hua Yan, Xiao-Jun Huang, Kai-Yan Liu, Xiao-Dong Mo, Huan Chen, and Jing-Zhi Wang
- Subjects
Adult ,Male ,China ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Disease ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,In patient ,Risk factor ,Child ,Antilymphocyte Serum ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,General Medicine ,Middle Aged ,medicine.disease ,Survival Analysis ,Anti-thymocyte globulin ,Leukemia, Myeloid, Acute ,Graft-versus-host disease ,Child, Preschool ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Female ,business ,030215 immunology - Abstract
Chronic graft-versus-host disease (cGVHD) is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia (n = 280). The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria. A total of 169 patients suffered from cGVHD. The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD (total, 66.0% vs. 53.7%, P = 0.031; moderate to severe, 42.4% vs. 30.1%, P = 0.036) than the patients who had 1 to 2 loci mismatched. The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD (49.2% vs. 32.9%, P = 0.024) compared with the patients who had other donors. The patients who had grades III to IV acute GVHD (aGVHD) had higher 8-year incidence of cGVHD (total, 88.0% vs. 50.4%, P < 0.001; moderate to severe, 68.0% vs. 27.0%, P < 0.001) compared with the patients without aGVHD. In multivariate analysis, grades III to IV aGVHD was the only independent risk factor for cGVHD. Thus, further interventions should be considered in patients with severe aGVHD to prevent cGVHD.
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- 2019
31. The prognostic significance of Wilms’ tumor gene 1 (WT1) expression at diagnosis in adults with Ph-negative B cell precursor acute lymphoblastic leukemia
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Yue-Yun Lai, Zongru Li, Xiao-Hui Zhang, Kai-Yan Liu, Hao Jiang, Qian Jiang, Ya-Zhen Qin, Xiao-Jun Huang, Lan-Ping Xu, Yu Wang, Yan-Rong Liu, and Xiao-Su Zhao
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Adult ,Male ,Oncology ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Lymphoblastic Leukemia ,urologic and male genital diseases ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Internal medicine ,Ph Negative ,medicine ,Humans ,Philadelphia Chromosome ,WT1 Proteins ,Gene ,B cell ,Chemotherapy ,Hematology ,Gene Expression Regulation, Leukemic ,urogenital system ,business.industry ,fungi ,Wilms' tumor ,General Medicine ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Survival Rate ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Hyperdiploidy ,business ,030215 immunology - Abstract
The prognostic significance of Wilms’ tumor gene 1 (WT1) expression at diagnosis in adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly understood. A total of 257 adults with Ph-negative BCP-ALL who were consecutively diagnosed and received at least 1 course of induction therapy at our institute were retrospectively analyzed. The WT1 expression patterns were significantly different among the molecularly and cytogenetically defined groups (E2A-PBX1, TEL-AML1, and MLL rearrangements; high hyperdiploidy and B-other). By considering the WT1 expression pattern and the relapse status, 2 cutoff values, 1.8% and 7.2%, were arbitrarily selected to place patients into WT1-low, WT1-inter, and WT1-high groups. In the B-other patients who achieved complete remission (CR), WT1-low and WT1-high patients had similar 3-year relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS) rates, which were all significantly lower than those of WT1-inter patients. The combined WT1-low/high expression group (n = 132) had significantly lower 3-year RFS, DFS, and OS rates compared with the WT1-inter group (n = 63) of B-other patients (RFS and DFS all P
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- 2019
32. Selecting slip resistant winter footwear for personal support workers
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Yue Li, Katherine Rizzi, Paul Holyoke, Geoff R. Fernie, Nidhi Patel, Zahra S. Bagheri, Tilak Dutta, and Kai Yan Grace Lui
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Adult ,Male ,Computer science ,Outdoor workers ,icy surfaces ,Survey result ,Slip (materials science) ,Transport engineering ,03 medical and health sciences ,0302 clinical medicine ,outdoor workers ,Snow ,Surveys and Questionnaires ,falls ,Slips ,Humans ,0501 psychology and cognitive sciences ,050107 human factors ,Ontario ,05 social sciences ,Rehabilitation ,Ice ,Public Health, Environmental and Occupational Health ,Home Health Aides ,Slip resistance ,Middle Aged ,030210 environmental & occupational health ,Purchasing ,Shoes ,footwear ,homecare workers ,Accidental Falls ,Female ,Seasons ,Research Article - Abstract
Background Falls are among the leading causes of occupational injuries for workers exposed to outdoor winter conditions such as Personal Support Workers (PSWs). Slip resistant footwear is known to reduce the risk of falls, however, it is difficult to predict how well a particular boot will perform prior to purchasing them. Our recently developed Maximum Achievable Angle (MAA) test can be used to rate footwear objectively to address this gap. Objective To rate the slip resistance of a selection of winter footwear that meets the needs and preferences of PSWs. Methods We selected 40 representative types of footwear based on survey results from 677 PSWs and applied our MAA test to rate slip resistance. Results Comfort and slip resistance were rated the most important features for selecting winter footwear. Of the 40 types of footwear tested, six were found to have a good slip resistance on ice. Conclusion The vast majority of winter footwear that meet the needs and preferences of PSWs, perform poorly on ice. Therefore, PSWs should consult our website (ratemytreads.com) for selecting appropriate footwear that will keep them safe in the winter.
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- 2019
33. Who is the best haploidentical donor for acquired severe aplastic anemia? Experience from a multicenter study
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Chen-Hua Yan, Yu-Hong Chen, Xiao-Dong Mo, Ming Zhou, Yan-Ru Ma, Kai-Yan Liu, Yuan-Yuan Zhang, Yuping Zhang, Xiao-Jun Huang, Sujun Gao, Wenjian Mo, Yu Wang, Xiao-Hui Zhang, Yi-Fei Cheng, Shunqing Wang, and Lan-Ping Xu
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Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Haploidentical transplantation ,medicine.medical_treatment ,Acquired severe aplastic anemia ,Hematopoietic stem cell transplantation ,lcsh:RC254-282 ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Sibling ,Aplastic anemia ,Child ,Molecular Biology ,Hematology ,Performance status ,business.industry ,Donor selection ,Proportional hazards model ,lcsh:RC633-647.5 ,Research ,Incidence (epidemiology) ,Anemia, Aplastic ,Infant ,lcsh:Diseases of the blood and blood-forming organs ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Tissue Donors ,Survival Rate ,030104 developmental biology ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Transplantation, Haploidentical ,Female ,business - Abstract
Background Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. Methods We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. Results Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0–1), or moderate graft mononuclear cell (MNC) counts (6–10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0–1). Conclusions Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.
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- 2019
34. The Quantification of Minimal Residual Disease Pre‐ and Post‐Unmanipulated Haploidentical Allograft by Multiparameter Flow Cytometry in Pediatric Acute Lymphoblastic Leukemia
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Yu-Hong Chen, Fei-Fei Tang, Xiao-Dong Mo, Lan-Ping Xu, Qiao-Zhen Fan, Huan Chen, Yu-Qian Sun, Ying-Jun Chang, Wei Han, Xiao-Jun Huang, Feng-Rong Wang, Xiao-Hui Zhang, Chen-Hua Yan, Yan-Rong Liu, Yu Wang, Xin-Yu Wang, and Kai-Yan Liu
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Neoplasm, Residual ,Histology ,Multivariate analysis ,Adolescent ,Gastroenterology ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Risk groups ,Pediatric Acute Lymphoblastic Leukemia ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Multiparameter flow cytometry ,Child ,Pre and post ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Cell Biology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Allografts ,Flow Cytometry ,Minimal residual disease ,body regions ,Lower incidence ,030104 developmental biology ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,business - Abstract
BACKGROUND This study aimed to determine the impact of the pre- and post-minimal residual disease (MRD) status as well as the peri-transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts. METHODS A retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry. RESULTS Pediatric ALL patients with pre-MRDneg had a lower cumulative incidences of relapse (CIR) compared to those with pre-MRDpos (19.7% vs. 41.2%, P = 0.009). Compared to post-MRDneg group, patients with post-MRDpos experienced higher CIR (81.0% vs. 15.9%, P
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- 2019
35. Allogeneic Hematopoietic Stem Cell Transplantation, Especially Haploidentical, May Improve Long-Term Survival for High-Risk Pediatric Patients with Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia in the Tyrosine Kinase Inhibitor Era
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Yu-Juan Xue, Huan Chen, Ying-Xi Zuo, Ai-Dong Lu, Xiao-Jun Huang, Yu-Qian Sun, Chen-Hua Yan, Wei Han, Pan Suo, Lan-Ping Xu, Yu Wang, Le-Ping Zhang, Yu-Hong Chen, Yue-Ping Jia, Yi-Fei Cheng, Jun Wu, and Kai-Yan Liu
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Male ,Oncology ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Philadelphia Chromosome ,Cumulative incidence ,Child ,Protein Kinase Inhibitors ,Transplantation ,Chemotherapy ,Philadelphia Chromosome Positive ,business.industry ,Hematopoietic Stem Cell Transplantation ,Infant ,Imatinib ,Induction Chemotherapy ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Allografts ,Hematologic Response ,Survival Rate ,surgical procedures, operative ,Child, Preschool ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Female ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly haploidentical (haplo)-HSCT, in pediatric patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in the tyrosine kinase inhibitor (TKI) era is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of Ph+ ALL in the TKI era. We analyzed clinical data of Ph+ ALL patients aged 1 to 18 years who received imatinib added to intensive chemotherapy at the start of induction therapy. Among the 68 patients who completed at least 2 consolidation cycles, 44 underwent transplantation (transplant arm) and 24 received continuous TKI with chemotherapy (nontransplant arm). At the 3-year follow-up the cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 23.5%, 73.4%, and 80.3%, respectively. Multivariate analysis showed that hematologic response (whether complete remission [CR] was achieved) at the induction end, BCR-ABL levels (whether major molecular response [MMR] was achieved) at 3 months, and transplantation were independent affecting factors for CIR, EFS, and OS. In the risk stratification analysis based on the first 2 prognostic factors mentioned above, no significant difference existed between the transplant and nontransplant arms for the probabilities of 3-year OS, EFS, and CIR in the standard-risk group (no poor prognostic factors). Meanwhile, OS, EFS, and CIR rates were significantly better in the transplant arm in the high-risk group (≥1 poor prognostic factor). Among the 44 patients in the transplant arm, 37 underwent haplo-HSCT. Achieving CR at the induction end, MMR at 3 months, and haplo-transplant were also independent favorable factors of CIR, EFS, and OS in the nontransplant and haplo-HSCT arms. Haplo-HSCT showed a significant survival advantage in the high-risk group only. Hematologic response at the induction end and BCR-ABL levels at 3 months are likely to be useful for identifying pediatric Ph+ ALL patients at a high risk of relapse in the TKI era. Children with Ph+ ALL in first CR may benefit from allo-HSCT, particularly those at high risk. Haplo-HSCT could achieve good long-term survival for pediatric Ph+ ALL. Thus, haplo-HSCT can be an alternative approach for high-risk Ph+ ALL patients.
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- 2019
36. High aldehyde dehydrogenase activity at diagnosis predicts relapse in patients with t(8;21) acute myeloid leukemia
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Yan Chang, Ya-Zhe Wang, Yan-Rong Liu, Yan-Huan Zhang, Xiao-Hui Zhang, Ya-Zhen Qin, Wen-Min Chen, Kai-Yan Liu, Feng-Ting Dao, Qian Jiang, Xiao-Jun Huang, and Lu Yang
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Neoplasm, Residual ,t(8 ,21) acute myeloid leukemia ,Chromosomes, Human, Pair 21 ,CD34 ,Aldehyde dehydrogenase ,CD38 ,Transcript level ,Gastroenterology ,Translocation, Genetic ,RUNX1 Translocation Partner 1 Protein ,0302 clinical medicine ,hemic and lymphatic diseases ,Child ,Original Research ,relapse ,biology ,medicine.diagnostic_test ,Myeloid leukemia ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Leukemia, Myeloid, Acute ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Core Binding Factor Alpha 2 Subunit ,Female ,Chromosomes, Human, Pair 8 ,Adult ,medicine.medical_specialty ,Adolescent ,RUNX1‐RUNX1T1 ,lcsh:RC254-282 ,Flow cytometry ,Young Adult ,03 medical and health sciences ,aldehyde dehydrogenase ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Aged ,business.industry ,flow cytometry ,Clinical Cancer Research ,Survival Analysis ,Minimal residual disease ,body regions ,030104 developmental biology ,Multivariate Analysis ,minimal residual disease ,biology.protein ,Neoplasm Recurrence, Local ,business - Abstract
Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Although the detection of minimal residual disease (MRD), which is indicated by RUNX1‐RUNX1T1 transcript levels, plays a key role in directing treatment, risk stratification needs to be improved, and other markers need to be assessed. A total of 66 t(8;21) AML patients were tested for aldehyde dehydrogenase (ALDH) activity by flow cytometry at diagnosis, and 52 patients were followed up for a median of 20 (1‐34) months. The median percentage of CD34+ALDH+, CD34+CD38‐ALDH+, and CD34+CD38+ALDH+ cells among nucleated cells were 0.028%, 0.012%, and 0.0070%, respectively. The CD34+ALDH+‐H, CD34+CD38‐ALDH+‐H, and CD34+CD38+ALDH+‐H statuses (the percentage of cells that were higher than the individual cutoffs) were all significantly associated with a lower 2‐year relapse‐free survival (RFS) rate in both the whole cohort and adult patients (P = .015, .016, and .049; P = .014, .018, and .032). Patients with, ALDH status at diagnosis may improve MRD‐based risk stratification in t(8;21) AML, and concurrent high levels of CD34 + ALDH+ at diagnosis and MRD predict relapse.
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- 2019
37. Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation
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Xiao-Dong Mo, Xiao-Jun Huang, Chen-Hua Yan, Jing-Zhi Wang, Yu Wang, Wei Han, Yu-Hong Chen, Lan-Ping Xu, Kai-Yan Liu, Feng-Rong Wang, Xiao-Hui Zhang, and Huan Chen
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Granulocyte ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,HLA Antigens ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,Humans ,Transplantation, Homologous ,Medicine ,Cumulative incidence ,Child ,Chemotherapy ,Leukemia ,Hematology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Interferon-alpha ,General Medicine ,Immunotherapy ,Middle Aged ,Survival Analysis ,Minimal residual disease ,Leukocyte Transfusion ,medicine.anatomical_structure ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology - Abstract
The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon-α (IFN- α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied (n = 47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P = 0.377) and 9.1% and 0.0% (P = 0.985) for patients in the IFN-α and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P = 0.891) and 84.3% and 84.6% (P = 0.972) for patients in the IFN-α and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN-α treatment.
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- 2019
38. MAGE genes: Prognostic indicators in AL amyloidosis patients
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Kai-Yan Liu, Lei Wen, Jin Lu, Guo-Rui Ruan, Xiao-Jun Huang, Yang Liu, Ling Ma, and Ying Kang
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,endocrine system ,Amyloid ,cancer‐testis antigen gene ,Plasma cell ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Antigens, Neoplasm ,Internal medicine ,Gene expression ,medicine ,AL amyloidosis ,Humans ,Immunoglobulin Light-chain Amyloidosis ,real‐time quantitative polymerase chain reaction ,neoplasms ,Multiple myeloma ,Aged ,Aged, 80 and over ,business.industry ,Amyloidosis ,Therapeutic effect ,amyloid light‐chain amyloidosis ,Cell Biology ,Original Articles ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,030104 developmental biology ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,030220 oncology & carcinogenesis ,Molecular Medicine ,Original Article ,Female ,business - Abstract
A high frequency of MAGE‐CT (cancer testis) antigens are expressed in Multiple Myeloma (MM) patients; however, in other plasma cell dyscrasias, their potential function remains unclear. We measured the expression of MAGE‐CT genes (MAGE‐C1/CT7, MAGE‐A3, MAGE‐C2/CT10) in 105 newly diagnosed amyloid light‐chain (AL) amyloidosis patients between June 2013 and January 2018 at Peking University People's Hospital using real‐time quantitative polymerase chain reaction. In the newly diagnosed AL patients, the positive expression rates of patients with MAGE‐C1/CT7, MAGE‐C2/CT10 and MAGE‐A3 were 83.8% (88/105), 56.71% (38/67) and 22.0% (13/59) respectively. There was no significant correlation between organ propensity and MAGE‐CT gene expression. Changes in the MAGE‐C1/CT7 levels were consistent with a therapeutic effect. The expression levels of MAGE‐C1/CT7, MAGE‐C2/CT10 and MAGE‐A3 provide potentially effective clinical indicators for auxiliary diagnoses and monitoring treatment efficacy in AL amyloidosis patients.
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- 2019
39. Occurrence and Severity of Donor Lymphocyte Infusion–Associated Chronic Graft-versus-Host Disease Influence the Clinical Outcomes in Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation
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Wen-Jing Yu, Yu-Hong Chen, Yu Wang, Xiao-Dong Mo, Feng-Rong Wang, Huan Chen, Chen-Hua Yan, Xiao-Hui Zhang, Kai-Yan Liu, Jing-Zhi Wang, Lan-Ping Xu, Wei Han, and Xiao-Jun Huang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Antineoplastic Agents ,Graft vs Leukemia Effect ,Hematopoietic stem cell transplantation ,Gastroenterology ,Donor lymphocyte infusion ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Aged ,Transplantation ,Chemotherapy ,Acute leukemia ,Leukemia ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Treatment Outcome ,Graft-versus-host disease ,Close relationship ,Lymphocyte Transfusion ,030220 oncology & carcinogenesis ,Acute Disease ,Chronic Disease ,Cohort ,Female ,business ,030215 immunology - Abstract
The aim of this study was to investigate the occurrence and severity of chemotherapy plus donor lymphocyte infusion (Chemo-DLI)-associated chronic graft-versus-host disease (cGVHD) in a consecutive cohort of patients with acute leukemia who experienced relapse after allogeneic hematopoietic stem cell transplantation (n = 104). The 5-year cumulative incidence of complete remission after Chemo-DLI was 81.0% (95% CI, 73.3% to 88.7%) and 84.6% (95% CI, 74.5% to 94.7%) in the moderate and severe cGVHD groups, respectively, which was significantly higher than that of the mild cGVHD group at 40.9% (95% CI, 29.3% to 52.5%) and non-cGVHD group at 29.2% (95% CI 23.1% to 35.3%). The cumulative incidence of nonrelapse mortality was comparable between patients with and without cGVHD. The 5-year probabilities of progression-free survival after Chemo-DLI were 42.9% (95% CI, 26.2% to 70.2%) and 34.6% (95% CI, 15.3% to 78.2%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI, 2.4% to 34.1%) and non-cGVHD group at 8.3% (95% CI 3.3% to 21.3%). The 5-year probabilities of overall survival after Chemo-DLI were 56.7% (95% CI, 38.9% to 82.7%) and 43.1% (95% CI, 22.1% to 84.0%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI 1.8% to 47.1%) and non-cGVHD group at 14.9% (95% CI, 7.3% to 30.2%). Our observations highlight the close relationship between cGVHD and immune-mediated graft-versus-leukemia (GVL) effect in patients with relapse receiving Chemo-DLI; however, mild cGVHD may not be associated with a sufficiently strong GVL effect to induce remission and improve survival.
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- 2019
40. Feeding difficulty is the dominant feature in 12 Chinese newborns with CHD7 pathogenic variants
- Author
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Huijun Wang, Guoqiang Chen, Xiang Chen, Lin Yang, Kai Yan, Wenhao Zhou, Bingbing Wu, Yanyan Gao, and Qian Qin
- Subjects
0301 basic medicine ,Male ,Pediatrics ,Choanal atresia ,030105 genetics & heredity ,Cohort Studies ,CHARGE syndrome ,Variant ,Genetics (clinical) ,Sanger sequencing ,Coloboma ,education.field_of_study ,High-Throughput Nucleotide Sequencing ,DNA-Binding Proteins ,Phenotype ,Cohort ,symbols ,Female ,Research Article ,medicine.medical_specialty ,China ,lcsh:Internal medicine ,lcsh:QH426-470 ,Feeding difficulty ,Population ,Feeding and Eating Disorders ,03 medical and health sciences ,symbols.namesake ,Neonatal Screening ,CHD7 gene ,Asian People ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,lcsh:RC31-1245 ,business.industry ,Cytogenetics ,DNA Helicases ,Infant, Newborn ,medicine.disease ,Newborn ,lcsh:Genetics ,030104 developmental biology ,ROC Curve ,Mutation ,Occipital lobe ,business - Abstract
Background CHARGE syndrome is characterized by coloboma, heart defects, choanal atresia, growth retardation, genitourinary malformation and ear abnormalities. The chromodomain helicase DNA-binding protein 7 (CHD7) gene is the major cause of CHARGE syndrome and is inherited in an autosomal dominant manner. Currently, the phenotype spectrum of CHARGE syndrome in neonatal population remain elusive. We aimed to investigate the phenotype spectrum of neonatal patients suspected to have CHARGE syndrome with pathogenic or likely pathogenic variants in the CHD7 gene. Methods We pooled next-generation sequencing data from the Neonatal Birth Defects Cohort (NBDC, ClinicalTrials.gov Identifier: NCT02551081) in Children’s Hospital of Fudan University. The pathogenicity of novel variants was analyzed by bioinformatic and genetic analyses. Clinical information collection, Sanger sequencing and follow-up interviews were performed when possible. Cranial MRI of these patients was performed, the volumes of different regions of the brain were analyzed. Results A total of 12 unrelated patients in our cohort were found with CHD7 variants. Eight patients received a firm clinical diagnosis of CHARGE syndrome (Bergmann criteria, Blake criteria, Verloes criteria and Hale criteria). Three patients did not match any diagnostic criteria, and no patients matched the Verloes criteria. Phenotype spectrum analysis found that feeding difficulty was the dominant feature among this neonatal cohort. Six novel variants in the CHD7 gene (Glu2408*, Lys651*, c.5607 + 1G > T, Leu373Val, Lys2005Asnfs*37 and Gln1991*) were identified, expanding the variant database of the CHD7 gene. Cranial MRI analysis revealed significant volume loss in cingulate gyrus, occipital lobe, and cerebellum and volume gain in the left medial and inferior temporal gyri anterior white matter parts. Conclusions Based on a relatively unbiased neonatal cohort, we concluded that CHARGE syndrome and CHD7 gene variants should be suspected in newborns who have feeding difficulty, and one or more malformations. Trial registration Neonatal Birth Defects Cohort (NBDC, ClinicalTrials.gov identifier: NCT02551081). Electronic supplementary material The online version of this article (10.1186/s12881-019-0813-z) contains supplementary material, which is available to authorized users.
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- 2019
41. Prophylactic oral NAC reduced poor hematopoietic reconstitution by improving endothelial cells after haploidentical transplantation
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Yu-Qian Sun, Ying-Jun Chang, Yu Wang, Yuan Kong, Xiao-Dong Mo, Xiao-Hui Zhang, Kai-Yan Liu, Min-Min Shi, Lan-Ping Xu, Yuan-Yuan Zhang, and Xiao-Jun Huang
- Subjects
Adult ,Male ,Adolescent ,medicine.medical_treatment ,CD34 ,Administration, Oral ,Allopurinol ,Bone Marrow Cells ,Hematopoietic stem cell transplantation ,Pharmacology ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,chemistry.chemical_classification ,Transplantation ,Reactive oxygen species ,business.industry ,Hematopoietic Stem Cell Transplantation ,Endothelial Cells ,Hematology ,Middle Aged ,Allografts ,Acetylcysteine ,Hematopoiesis ,Clinical trial ,Haematopoiesis ,surgical procedures, operative ,medicine.anatomical_structure ,Cellular Microenvironment ,chemistry ,Female ,Bone marrow ,business ,medicine.drug - Abstract
Poor graft function (PGF) and prolonged isolated thrombocytopenia (PT) remain life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Endothelial cells (ECs) play a crucial role in regulating hematopoiesis in the bone marrow (BM) microenvironment. However, whether the impaired BM ECs are responsible for defective hematopoiesis in PGF and PT patients requires clarification, and clinical management is challenging. Two prospective clinical trials were included in the current study. In the first trial (N = 68), PGF and PT patients demonstrated defective BM ECs pre-HSCT and impaired BM EC dynamic reconstitution at early time points post-HSCT, which was positively correlated with reactive oxygen species (ROS) levels. Receiver operating characteristic curves showed that BM EC < 0.1% pre-HSCT could identify high-risk patients with PGF and PT. The second trial enrolled patients (N = 35) with EC < 0.1% who accepted oral N-acetyl-l-cysteine (NAC; 400 mg 3 times per day) from −14 days pre-HSCT to +2 months post-HSCT continuously, whereas the remaining EC ≥ 0.1% patients (N = 39) received allo-HSCT only. Prophylactic NAC intervention was safe and effective in preventing the occurrence of PGF and PT in EC < 0.1% patients by promoting the dynamic reconstitution of BM ECs and CD34+ cells, along with reducing their ROS levels, which was further confirmed by in situ BM trephine biopsy analyses. These findings suggest that the impaired BM ECs pre-HSCT are responsible for the defective hematopoiesis in PGF and PT patients. Therefore, improvement of BM ECs through prophylactic NAC intervention may be a promising therapeutic approach to promote hematopoietic reconstitution post-HSCT. This trial was registered at www.clinicaltrials.gov as #NCT03236220 and #NCT02978274.
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- 2019
42. Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem cell transplantation
- Author
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Li-Juan Hu, Xiao-Dong Mo, Xiao-Hui Zhang, Huan Chen, Chen-Hua Yan, Hui Wang, Lan-Ping Xu, Qi Wang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang, and Yu-Hong Chen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,Platelet Engraftment ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,Disease-Free Survival ,Feces ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,Bloodstream infection ,Risk of mortality ,medicine ,Overall survival ,Humans ,Cumulative incidence ,Child ,Aged ,Candida ,Retrospective Studies ,Positive stool culture ,business.industry ,digestive, oral, and skin physiology ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Middle Aged ,Child, Preschool ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Female ,business ,030215 immunology - Abstract
We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) (n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group; 19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens.
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- 2019
43. Assessing negative symptoms in schizophrenia: Validity of the clinical assessment interview for negative symptoms in Singapore
- Author
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Gurpreet Rekhi, Caryn Kai Yan Yuen, Mei San Ang, Wai Yee Ng, Jimmy Lee, and Lee Kong Chian School of Medicine (LKCMedicine)
- Subjects
Adult ,Male ,Psychometrics ,Alogia ,03 medical and health sciences ,Clinical Assessment Interview ,0302 clinical medicine ,Cronbach's alpha ,Interview, Psychological ,medicine ,Humans ,Medicine [Science] ,Scale for the Assessment of Negative Symptoms ,Biological Psychiatry ,Psychiatric Status Rating Scales ,Singapore ,Positive and Negative Syndrome Scale ,Discriminant validity ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Exploratory factor analysis ,Confirmatory factor analysis ,030227 psychiatry ,Psychiatry and Mental health ,Schizophrenia ,Female ,medicine.symptom ,Factor Analysis, Statistical ,Psychology ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
This study aimed to examine the validity of the Clinical Assessment Interview for Negative Symptoms (CAINS) in Singapore. 274 participants with schizophrenia were assessed on the CAINS, Scale for the Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Social and Occupational Functioning Assessment Scale (SOFAS) and the Simpson-Angus Extrapyramidal Side Effects Scale (SES). Factor analyses were conducted and Cronbach's coefficient alpha was calculated. Spearman's correlation coefficient was used to assess correlations. The 2-factor model of the CAINS failed to fit our data. Exploratory factor analysis of a randomly selected split-half of the sample yielded four factors: motivation-pleasure (MAP) social, MAP vocational, MAP recreational and expression (EXP), accounting for 73.94% of the total variance. Confirmatory factor analysis on the remaining sample supported this factor structure. Cronbach's alpha for the CAINS was 0.770. Significant correlations were observed between the CAINS total and the SANS total and PANSS negative subscale scores. Good divergent validity was shown by insignificant correlations with PANSS positive subscale score and CDSS total score. The MAP social and recreational factor scores had moderate correlations with the SANS anhedonia-asociality subscale scores, whereas the MAP vocational factor had the highest correlation with the avolition-apathy subscale of the SANS. EXP factor score correlated strongly with the SANS affective flattening and alogia subscales scores. In conclusion, the CAINS has good psychometric properties and can be used by clinicians to assess negative symptoms in individuals with schizophrenia in the local population. Published version
- Published
- 2019
44. Myeloablative Haploidentical Transplantation Is Superior to Chemotherapy for Patients with Intermediate-risk Acute Myelogenous Leukemia in First Complete Remission
- Author
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Yu-Qian Sun, Hao Jiang, Yu Wang, Qian Jiang, Lan-Ping Xu, Hong-Hu Zhu, Huan Chen, Xiao-Dong Mo, Feng-Rong Wang, Jin Lu, Kai-Yan Liu, Xiao-Jun Huang, Wei Han, Jing-Zhi Wang, Meng Lv, Xiao-Hui Zhang, Yao Chen, Ting Zhao, Chen-Hua Yan, Jinsong Jia, Yuan-Yuan Zhang, Jing Wang, and Ying-Jun Chang
- Subjects
Adult ,Male ,Oncology ,endocrine system ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Myeloid ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Living Donors ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,Chemotherapy ,business.industry ,Incidence ,Siblings ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Myeloablative Agonists ,medicine.disease ,Minimal residual disease ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Transplantation, Haploidentical ,Female ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
Purpose: Although myeloablative HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. Patients and Methods: In this prospective trial, among 443 consecutive patients ages 16–60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n = 69) or underwent haplo-HSCT (n = 78). Results: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; P = 0.0004 and 80.8% vs. 53.5%; P = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163–0.793; P = 0.011], OS (HR 0.361; 95% CI, 0.156–0.832; P = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057–0.459; P = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. Conclusions: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.
- Published
- 2019
45. A multi-stage association study of plasma cytokines identifies osteopontin as a biomarker for acute coronary syndrome risk and severity
- Author
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Xinwen Min, Binyao Yang, Kuai Yu, Tangchun Wu, Xuezhen Liu, Ce Zhang, Lue Zhou, Kai Yan, Xiulou Li, Liyun Zhang, Haijing Jiang, Xiaoting Luo, Xiang Cheng, Xiaomin Zhang, Jun Li, An Pan, Shunchang Sun, Frank B. Hu, Meian He, Wenhua Mei, and Handong Yang
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Acute coronary syndrome ,Science ,Severity of Illness Index ,Article ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Severity of illness ,medicine ,Humans ,Prospective Studies ,Osteopontin ,Acute Coronary Syndrome ,Prospective cohort study ,Aged ,Multidisciplinary ,Framingham Risk Score ,biology ,business.industry ,Brain-Derived Neurotrophic Factor ,Odds ratio ,Middle Aged ,medicine.disease ,C-Reactive Protein ,030104 developmental biology ,biology.protein ,Biomarker (medicine) ,Medicine ,Female ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Cytokines play a critical role in the pathogenesis and development of cardiovascular diseases. However, data linking cytokines to risk and severity of acute coronary syndrome (ACS) are still limited. We measured plasma profile of 280 cytokines using a quantitative protein microarray in 12 ACS patients and 16 healthy controls, and identified 15 differentially expressed cytokines for ACS. Osteopontin, chemokine ligand 23, brain derived neurotrophic factor and C-reactive protein (CRP) were further validated using immunoassay in two independent case-control studies with a total of 210 ACS patients and 210 controls. We further examined their relations with incident ACS among 318 case-control pairs nested within the Dongfeng-Tongji cohort, and found plasma osteopontin and CRP concentrations were associated with incident ACS, and the multivariable-adjusted odds ratio (95% confidence interval) was 1.29 (1.06–1.57) per 1-SD increase for osteopontin and 1.30 (1.02–1.66) for CRP, respectively. Higher levels of circulating osteopontin were also correlated with higher severity of ACS, and earlier ACS onset time. Adding osteopontin alone or in combination with CRP modestly improved the predictive ability of ACS beyond the Framingham risk scores. Our findings suggested that osteopontin might be a biomarker for incident ACS, using osteopontin adds moderately to traditional cardiovascular risk factors.
- Published
- 2019
46. Effects of Low-Dose Glucocorticoid Prophylaxis on Chronic Graft-versus-Host Disease and Graft-versus-Host Disease–Free, Relapse-Free Survival after Haploidentical Transplantation: Long-Term Follow-Up of a Controlled, Randomized Open-Label Trial
- Author
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Huan Chen, Xiao-Hui Zhang, Xiao-Jun Huang, Kai-Yan Liu, Xiao-Dong Mo, Chen-Han Yan, Fei-Fei Tang, Lan-Ping Xu, Yu Wang, Wei Han, Feng-Rong Wang, Yu-Qian Sun, Yu-Hong Chen, and Ying-Jun Chang
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Premedication ,Graft vs Host Disease ,Infections ,Methylprednisolone ,Gastroenterology ,Disease-Free Survival ,Group B ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Femur Head Necrosis ,law ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Glucocorticoids ,Transplantation ,business.industry ,Hazard ratio ,Hematology ,Middle Aged ,medicine.disease ,Graft-versus-host disease ,030220 oncology & carcinogenesis ,Transplantation, Haploidentical ,Corticosteroid ,Female ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n = 83, group A) or high risk; patients at high risk were randomly assigned to receive (n = 72, group B) or not receive (n = 73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .010), herpes zoster infection (28% versus 12%; P = .010), pulmonary infections (42% versus 21%; P = .040), and osteonecrosis of the femoral head (ONFH; 16% versus 6%; P = .045) as well as better GRFS (59% versus 33%; P = .017). Factors associated with GRFS included total dose of corticosteroid used in the first 100days after transplantation (hazard ratio, 1.547; P = .015) and platelet recovery (hazard ratio, 1.456; P = .037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH and a superior GRFS, indicating that higher steroid doses are harmful. Reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580.)
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- 2019
47. FLT3 internal tandem duplication does not impact prognosis after haploidentical allogeneic hematopoietic stem cell transplantation in AML patients
- Author
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Kai-Yan Liu, Chen-Hua Yan, Feng-Rong Wang, Xiao-Dong Mo, Jing-Zhi Wang, Yu Wang, Xiao-Hui Zhang, Yuan-Yuan Zhang, Xiao-Jun Huang, Yu-Qian Sun, Huan Chen, Wei Han, Lan-Ping Xu, and Yu-Hong Chen
- Subjects
Adult ,Male ,Acute promyelocytic leukemia ,Oncology ,FLT3 Internal Tandem Duplication ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,03 medical and health sciences ,Myelogenous ,0302 clinical medicine ,Leukemia, Promyelocytic, Acute ,hemic and lymphatic diseases ,White blood cell ,Internal medicine ,medicine ,Humans ,Child ,Survival rate ,Aged ,Transplantation ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Allografts ,medicine.disease ,Survival Rate ,Leukemia ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,Child, Preschool ,030220 oncology & carcinogenesis ,Mutation ,Female ,business ,psychological phenomena and processes ,Follow-Up Studies ,030215 immunology - Abstract
Acute myelogenous leukemia (AML) patients with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) have poor prognoses if treated with chemotherapy only, primarily as they experience increased relapse rates. To determine whether this alteration also affects outcomes after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT), we compared 334 consecutive FLT3-ITD-positive vs -negative patients with AML (other than acute promyelocytic leukemia) who underwent HID-HSCT. FLT3-ITD was detected in 39 of 334 patients (11.7%). The 2-year relapse rates for FLT3-ITD-positive and -negative patients were 16% and 17%, respectively (P = 0.774). The 3-year disease-free survival (DFS) rates for FLT3-ITD-positive and -negative patients were 74% (95% confidence interval [CI]: 64-81) and 73% (95% CI: 70-81), respectively; P = 0.872); while the 3-year overall survival (OS) rates were 72% (95% CI: 67-81) and 77% (95% CI: 72-84), respectively (P = 0.862). FLT3-ITD mutation had no influence on non-relapse mortality (NRM 15% vs 14%, P = 0.463). Multivariate analyses showed that disease status at HSCT and white blood cell count at diagnosis were independent risk factors associated with relapse, DFS, and OS. In conclusion, FLT3 mutation status has no impact on outcomes after HID-HSCT in patients with AML. HID-HSCT is therefore a valid option for AML patients with FLT3-ITD mutation.
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- 2019
48. Eltrombopag is an effective and safe therapy for refractory thrombocytopenia after haploidentical hematopoietic stem cell transplantation
- Author
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Wei Han, Yu-Qian Sun, Xiao-Dong Mo, Ting-Ting Han, Kai-Yan Liu, Feng-Rong Wang, Jing-Zhi Wang, Yu Wang, Lan-Ping Xu, Xiao-Jun Huang, Hai-Xia Fu, Chen-Hua Yan, Xiao-Hui Zhang, Huan Chen, and Yuan-Yuan Zhang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Platelet Engraftment ,medicine.medical_treatment ,Eltrombopag ,Hematopoietic stem cell transplantation ,Benzoates ,Gastroenterology ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Megakaryocyte ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Platelet ,Cumulative incidence ,Refractory Thrombocytopenia ,Child ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Thrombocytopenia ,Hydrazines ,Treatment Outcome ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Transplantation, Haploidentical ,Pyrazoles ,Female ,business ,030215 immunology - Abstract
Refractory thrombocytopenia is a frequent and severe complication after haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) and lacks effective treatment strategies. Eltrombopag has shown promising results in several thrombocytopenia disorders. We report 38 patients treated with eltrombopag for refractory thrombocytopenia after haplo-HSCT. Eight patients had delayed platelet engraftment, 15 patients had secondary failure of platelet recovery, and 15 patients had poor graft function (PGF). Eltrombopag was initiated at 25 or 50 mg daily, and the dosage was adjusted to a maximum of 50–100 mg daily to maintain platelet between 50 × 109/L and 100 × 109/L. The cumulative incidence of platelet recovery to transfusion independence was 63.2% and to ≥50 × 109/L without transfusion support was 52.3%. Furthermore, neutrophil counts and hemoglobin were also increased in the nine responders with PGF. Nineteen (79.2%) of the 24 responders were able to taper off eltrombopag, and the remaining 5 patients were able to begin a taper. The median duration of treatment was 64 (range 14–195) days. The presence of megakaryocyte before initiation was the only independent factor influencing the efficacy of eltrombopag (P = 0.044). Eltrombopag was well tolerated in all patients. In summary, eltrombopag was a safe and effective therapy for refractory thrombocytopenia after haplo-HSCT.
- Published
- 2019
49. Visual–Vestibular Interaction for Postural Control During Sit-to-Stand: Effects of Aging
- Author
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Kai Yan Lui, Nandini Deshpande, and Patricia Hewston
- Subjects
Adult ,Male ,Aging ,Motion analysis ,medicine.medical_specialty ,Head (linguistics) ,Posture ,Physical Therapy, Sports Therapy and Rehabilitation ,Postural control ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Physiology (medical) ,otorhinolaryngologic diseases ,Linear acceleration ,Humans ,Medicine ,Postural Balance ,Vision, Ocular ,Aged ,Vestibular system ,Sit to stand ,business.industry ,Motor control ,Visual vestibular interaction ,030229 sport sciences ,Middle Aged ,Female ,Vestibule, Labyrinth ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
During sit-to-stand (STS), the vestibular system is highly stimulated in response to linear acceleration of the head and may play an important role, in addition to vision, for postural control. We examined the effects of aging on visual–vestibular interaction for postural control during STS in 15 young (22.5 ± 1.1 years) and 15 older (73.9 ± 5.3 years) participants. Vestibular information was manipulated using galvanic vestibular stimulation. Vision conditions involved normal (eyes open), suboptimal (blurring goggles), and no (eyes closed) vision. Older participants had significantly greater mediolateral peak-to-peak trunk roll (p = .025) and center of mass displacements (p
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- 2019
50. Hemofilter with Adsorptive Capacities: Case Report Series
- Author
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Songqiao Liu, Minmin Wang, Tiantian Wei, Ling Zhang, Yi Yang, Xinyu Liu, Ping Chang, Qiang Yao, Gloria Kai Yan Tang, Mark R. Marshall, Wai Ming Chan, and Jing Cai
- Subjects
Adult ,Male ,medicine.medical_specialty ,Critical Care ,030232 urology & nephrology ,Renal function ,030204 cardiovascular system & hematology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Sepsis ,Intensive care ,medicine ,Adjuvant therapy ,Humans ,Intensive care medicine ,Aged ,business.industry ,Standard treatment ,Acute kidney injury ,Hematology ,General Medicine ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Discontinuation ,Organ damage ,Nephrology ,Hemofiltration ,business ,Biomarkers - Abstract
Background: oXiris is a blood purification product that has been launched recently in China. In addition to renal function support and fluid management capabilities, it can also adsorb cytokines and endotoxins. This may complement standard treatment for septic acute kidney injury (AKI) patients to control the amplitude of systemic inflammatory response responsible for acute tissue and organ damage. Objectives of our study are to elucidate characteristics of septic AKI patients who respond to treatment with oXiris and to describe the performance of oXiris through patient cases in the absence of large randomized trials on clinical use of oXiris for septic AKI patients in China. Summary: Here, we present 4 cases managed in intensive care units of major hospitals in China. Key practical aspects from an expert meeting discussing these cases have been included as guidance for the use of oXiris in septic AKI patients. Key Messages: Based on the experience gathered from 4 cases, oXiris should be used early in the treatment of septic AKI patients as an adjuvant therapy with good infection source control. It should not be used to delay or replace infection source control. These cases also demonstrated that patients with high risk of bleeding can use oXiris without additional anticoagulation for up to 36 h without implications on serum protein levels and platelet count. Short of definitive biomarkers to gauge the ideal blood purification initiation and discontinuation time for septic AKI patients, clinical judgment is key to determining optimal use of oXiris in septic AKI patients.
- Published
- 2019
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