324 results on '"De-pei Wu"'
Search Results
2. Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial
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Yu Wang, Qi-Fa Liu, De-Pei Wu, Zheng-Li Xu, Ting-Ting Han, Yu-Qian Sun, Fen Huang, Zhi-Ping Fan, Na Xu, Feng Chen, Ye Zhao, Yuan Kong, Xiao-Dong Mo, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, and Xiao-Jun Huang
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Mini-dose ,Methotrexate ,Acute ,GVHD ,Medicine - Abstract
Abstract Background There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Methods We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. Results The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. Conclusions In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. Trial registration The trial was registered with clinicaltrials.gov (NCT04960644).
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- 2024
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3. Venetoclax plus hypomethylating agents in newly diagnosed acute myeloid leukemia patients with RUNX1::RUNX1T1: a retrospective propensity score matching study
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Miao Wang, Han-Yu Cao, Kai-Wen Tan, Qiao-Cheng Qiu, Yuan-Hong Huang, Shuai-shuai Ge, Zi-Hao Wang, Jia Chen, Xiao-Wen Tang, De-Pei Wu, Sheng-Li Xue, Zheng Li, and Hai-Ping Dai
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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4. Outcomes of venetoclax combined with homoharringtonine and cytarabine in fit adults patients with de novo adverse‐risk acute myeloid leukaemia: A single‐centre retrospective analysis
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Bao‐Quan Song, Xin Kong, Yan Pu, Yin Liu, Jian Zhang, De‐Pei Wu, and Hui‐Ying Qiu
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Acute myeloid leukemia ,Adverse‐risk ,Cytarabine ,Homoharringtonine ,Venetoclax ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Adverse‐risk acute myeloid leukemia (AML) has a dismal prognosis. We aimed to investigate the activity and tolerability of venetoclax combined with homoharringtonine (HHT) plus cytarabine (VHA) regimen for de novo adverse‐risk AML. Thirteen de novo AML patients with adverse‐risk factors were treated with venetoclax (100 mg day 1, 200 mg day 2, 400 mg days 3‐21), HHT (1 mg/m2 days 1‐5) and cytarabine (100 mg/m2 days 1‐5) (VHA regimen). Complete remission (CR) was achieved in 11/13 patient (84.6%), all of CR responders were measurable residual disease (MRD) negative detected by multi‐parameter flow cytometry (MFC). Grade 3‐4 neutropenia, anaemia, and thrombocytopenia occurred in most patients. Grade 3‐4 non haematological adverse events (AEs) included febrile neutropenia (4/13, 30.8%). With a median follow‐up of 10 months (range 4‐19), median overall survival and event‐free survival were not reached. VHA may be a promising and well‐tolerated regimen in de novo adverse‐risk AML.
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- 2023
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5. A clinical predictive model for pre-transplantation Klebsiella pneumoniae colonization and relevance for clinical outcomes in patients receiving allogeneic hematopoietic stem cell transplantation
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Yu-Qi Zhang, Wen-Qi Wu, Jie Xu, Zai-Xiang Tang, Shi-Jia Li, Ling Li, He-Qing Wu, Xiao Ma, Ji-Sheng Liu, De-Pei Wu, and Xiao-Jin Wu
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Klebsiella pneumoniae ,colonization ,hematopoietic stem cell transplantation ,bloodstream infections ,predictive model ,Microbiology ,QR1-502 - Abstract
ABSTRACTThe purpose of this study is to establish a clinical prediction model to discriminate patients at high risk of Klebsiella pneumoniae (KP) colonization before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and evaluate the impact of KP colonization on clinical outcomes after allo-HSCT. We retrospectively collected data from 2,157 consecutive patients receiving allo-HSCT between January 2018 and March 2022. KP colonization was defined as a positive test for KP from a pharyngeal or anal swab before allo-HSCT. Logistic regression was used to build a clinical prediction model. Cox regression analyses were performed to explore the effect of KP colonization on clinical outcomes. Among all the inpatients, 166 patients had KP colonization and 581 with no positive pathogenic finding before transplantation. Seven candidate predictors were entered into the final prediction model. The prediction model had an area under the curve of 0.775 (95% CI 0.723–0.828) in the derivation cohort and 0.846 (95% CI: 0.790–0.902) in the validation cohort. Statistically significantly different incidence rates were observed among patient groups with clinically predicted low, medium, and high risk for KP infection (P < 0.001). The presence of KP colonization delayed platelet engraftment (P < 0.001) and patients with KP colonization were more likely to develop KP bloodstream infections within 100 days after allo-HSCT (P < 0.0001). Patients with KP colonization had higher non-relapse mortality (P = 0.032), worse progression-free survival (P = 0.0027), and worse overall survival within 100 days after allo-HSCT (P = 0.013). Our findings suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted.IMPORTANCESeveral studies have identified that Klebsiella pneumoniae (KP) is among the most common and deadly pathogens for patients in hospital intensive care units and those receiving transplantation. However, there are currently no studies that evaluate the impact of KP colonization to patients undergoing allogeneic hematopoietic stem cell transplantation. Our results confirm that pre-existing KP colonization is relatively common in a hematology transplant ward setting and negatively affects post-transplantation prognosis. Our clinical prediction model for KP colonization can support early intervention in patients at high risk to avoid subsequent bloodstream infections and improve survival outcomes. Altogether, our data suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted. Future studies are needed to confirm these findings and to test early intervention strategies for patients at risk of complications from KP infection.
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- 2024
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6. Safety and efficacy of CD22 and CD19 CAR-T bridging auto-HSCT as consolidation therapy for AYA and adult B-ALL
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Yan Qiu, Chao-Ling Wan, Ming-Zhu Xu, Hai-Xia Zhou, Mei-Jing Liu, Wen-Jie Gong, Li-Qing Kang, Ai-Ning Sun, Lei Yu, De-Pei Wu, Chong-Sheng Qian, and Sheng-Li Xue
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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7. Combination of venetoclax with BCR-ABL tyrosine kinase inhibitor as a therapeutic strategy for Philadelphia chromosome-positive leukemias
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Jing-Ying Zou, Si-Man Huang, Hai-Xia Zhoub, Ming-Zhu Xu, Ai-Ning Sun, De-Pei Wu, Sheng-Li Xue, and Tong-Tong Zhang
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Philadelphia chromosome-positive leukemias ,combination of venetoclax with TKI ,hypomethylating agents ,efficacy ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
ABSTRACTObjectives: Venetoclax has shown synergism with BCR-ABL1 tyrosine kinase inhibitors (TKIs) in preclinical studies for patients with Philadelphia chromosome-positive (Ph+) leukemias. This combination may suggest a novel treatment strategy for Ph + leukemias.Methods: We conducted a retrospective study to summarize the activity of combining venetoclax and BCR-ABL1 TKI-based therapies in Ph + leukemias.Result: A total of 18 patients with Ph + leukemias were enrolled in this study. At the time of venetoclax and TKI-based therapy, 5 patients were initially diagnosed, with Ph + acute myeloid leukemia (AML) (n = 1) and mixed phenotype acute leukemia (MPAL) (n = 4), 7 patients had chronic myeloid leukemia at blastic phase (CML-BP), and the remaining 6 patients had relapsed or refractory to prior therapy. The overall response rate (ORR) was 88.9% (9 CR, 2 CRi, 4 MLFS, 1 PR), and a major molecular response (MMR) (or better) was achieved in 7 (38.8%) of all patients. With a median follow-up of 7.0 months (range, 2.3-15.6), 15 (83.3%) were in continuous CR at the time of this analysis, with a 1-year OS of 85.6%, 1-year LFS of 76.7%, and 1-year CIR of 22.4%. Moreover, 10 of 18 patients were treated with venetoclax, TKI and hypomethylating agent (HMA) regimens, which also associated with a high ORR rate (6 CR, 1 CRi, 3 MLFS), and can be used for induction or salvage therapy.Conclusion: Venetoclax and TKI-based combination regimens may be a feasible approach for Ph + leukemias, and prospective studies are needed to properly assess the safety, tolerability and efficacy of this regimen.
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- 2023
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8. CAR-T cell therapy followed by allogenic hematopoietic stem cell transplantation yielded comparable outcome between Ph like ALL and other high-risk ALL
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Hai-ping Dai, Dan-qing Kong, Hong-jie Shen, Wei Cui, Qian Wang, Zheng Li, Jia Yin, Li-qing Kang, Lei Yu, De-pei Wu, and Xiao-wen Tang
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Ph-like ,ALL ,Relapsed/refractory ,CAR-T therapy ,Allo-HSCT ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract It was previously believed that patients with Ph-like ALL had poorer prognosis compared with other B-ALL subgroups due to resistance to conventional chemotherapy and lack of targeted drugs. CAR-T therapy has been successfully applied in the treatment of relapsed and refractory B-ALL. Currently, there are few data on whether CAR-T therapy can alter the outcome of Ph-like ALL. Here we included 17 Ph-like, 23 Ph+ and 51 other B-ALL patients, who received autologous CAR T-cell therapy and subsequently allogenic stem cell transplantation. Patients in the Ph-like group and B-ALL-others group were younger that those in the Ph+ group (P=0.001). Ph-like and Ph+ ALL patients showed higher white blood cell counts at diagnosis (P=0.025). The percentage of patients with active disease before receiving CAR T-cells infusion was 64.7%, 39.1% and 62.7% in the Ph-like, Ph+ and B-ALL-others groups. The response rates to CAR-T therapy were 94.1% (16/17), 95.6% (22/23) and 98.0% (50/51) in the Ph-like, Ph+ and B-ALL-others groups. Measurable residual disease negative CR was achieved in 64.7% (11/17), 60.9% (14/23) and 54.9% (28/51) in the Ph-like, Ph+ and B-ALL-others groups, respectively. The estimated rates of 3-year overall survival (65.9%±16.5%, 59.7%±10.5% and 61.6%±7.3%, P=0.758) and 3-year relapse-free survival (59.8%±14.8%, 63.1%±10.5% and 56.3%±7.1%, P=0.764) were comparable among the Ph-like, Ph+ and B-ALL-others groups. Estimated 3-year cumulative relapse rate was 7.8%±0.6%, 23.4%±0.9% and 29.0%±0.4% (P=0.241). Our findings suggest that CART followed by allo-HSCT results in a comparable prognosis in Ph-like ALL and other high-risk B-ALL. Trial registration ClinicalTrials. gov, NCT03275493, Registered on September 7, 2017, prospectively registered and NCT03614858, Registered on August 3, 2018, prospectively registered.
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- 2023
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9. P1089: ZANUBRUTINIB-RITUXIMAB CHEMO-FREE THERAPY WITH OR WITHOUT AUTOLOGOUS STEM CELL TRANSPLANTATION IN NEWLY DIAGNOSED MANTLE CELL LYMPHOMA
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Chang-Ju Qu, Rui Zou, Jia-Jie He, Na-Na Ping, Qian Zhu, Xiao Zhang, Fan Xia, Danqing Kong, De-Pei Wu, and Zheng-Ming Jin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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10. P1196: ORIENT STUDY: REGIMEN OF ORELABRUTINIB PLUS R-CHOP-LIKE FOR PATIENTS WITH NEWLY DIAGNOSED UNTREATED NON-GCB DLBCL
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Chang-Ju Qu, Hai-Ling Liu, Rui Zou, Na-Na Ping, Qian Zhu, Xiao Zhang, Jia-Jie He, De-Pei Wu, and Zheng-Ming Jin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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11. Haploidentical CD7 CAR T-cells induced remission in a patient with TP53 mutated relapsed and refractory early T-cell precursor lymphoblastic leukemia/lymphoma
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Hai-ping Dai, Wei Cui, Qing-ya Cui, Wen-juan Zhu, Hui-min Meng, Min-qing Zhu, Xia-ming Zhu, Lin Yang, De-pei Wu, and Xiao-wen Tang
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Chimeric antigen receptor T-cells ,CD7 ,Early T-cell precursor lymphoblastic leukemia/lymphoma ,Relapsed / refractory ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Patients with relapsed/refractory early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) respond poorly to traditional therapy and have dismal prognosis. CD7 is a promising therapeutic targets for chimeric antigen receptor modified T cell therapy (CART) due to its widely expression in almost all T-cell malignancies. Here we present the anti-CD7 CART therapy in a 11-year-old male with TP53 mutated relapsed/refractory ETP-ALL/LBL. The patient suffered second relapse after haploidentical hematopoietic stem cell transplantation, showing resistance to 4 lines salvage therapies including venetoclax. Nanobody derived CD7-CART cells were manufactured by co-transducing CAR-T cells with a CD7 protein expression blocker. 70.5% of blasts (CD7 expression: 92.6%) and extensive extramedullary disease (mediastinal mass, enlarged lymph nodes and spleen) were observed prior to CD7-CART-cell therapy. A total of 5 × 106/kg donor-derived CD7-CART-cells were infused. Hematological and extramedullary remission were both achieved, with persistence of CD7-CART-cells be detected until the last followup at 96th days after the infusion. Reversible adverse effects including grade 3 cytokine release syndrome and macrophage activation syndrome were observed. This case demonstrated that CD7-CART was a potent and safe salvage therapy in relapsed/refractory ETP-ALL/LBL patient with high tumor burden. Trial registration: ClinicalTrials. gov, NCT04785833 , Registered on March 8, 2021, prospectively registered.
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- 2022
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12. Efficacy and safety of decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) for newly diagnosed acute myeloid leukemia
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Jun-Feng Zhu, Hai-Ping Dai, Qian-Qian Zhang, Jia Yin, Zheng Li, Qin-Ya Cui, Xiao-Peng Tian, Si-Ning Liu, Zheng-Ming Jin, Xia-Ming Zhu, De-Pei Wu, and Xiao-Wen Tang
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induction chemotherapy ,decitabine ,HAAG ,acute myeloid leukemia ,efficacy and safety ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The 7 + 3 regimen is the front-line induction chemotherapy in patients with newly diagnosed acute myeloid leukemia, with a response rate of 60-80%. But it’s not suitable for all patients especially old/unfit patients because of a higher treatment related toxicity. Therefore, safer and more effective induction therapies are required. In this retrospective study, 50 patients with newly diagnosed acute myeloid leukemia received decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) as induction chemotherapy. Complete remission (CR) rate was 96% (48/50) and overall response rate was 100%. Of note, All 7 patients harboring FLT3-ITD mutation achieved CR. The median overall survival (OS) was 40.0 months (range 2.0, 58.0). The OS at 1, 3, and 5 years were 75.3%, 54.2%, and 49.3%. The median relapse free survival (RFS) was 38.0 months (range 2.0, 58.0). The RFS at 1, 3, and 5 years were 67.3%, 48.9%, and 45.1%. The OS and RFS of patients who received hematopoietic stem cell transplantation (HSCT) were significantly higher than those who did not undergo HSCT (p=0.017; 0.016). The incidence of grade 3-4 neutropenia and thrombocytopenia was 84% and 88%. Meanwhile, the incidence of grade 3-4 infection and bleeding was only 16% and 6%. There was no early death. In conclusion, DAC+HAAG regimen is effective and well-tolerated as induction therapy in patients with newly diagnosed AML.
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- 2022
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13. The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update
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Xiao-hui Zhang, Jing Chen, Ming-Zhe Han, He Huang, Er-lie Jiang, Ming Jiang, Yong-rong Lai, Dai-hong Liu, Qi-Fa Liu, Ting Liu, Han-yun Ren, Yong-Ping Song, Zi-min Sun, Xiao-wen Tang, Jian-min Wang, De-pei Wu, Lan-ping Xu, Xi Zhang, Dao-bin Zhou, and Xiao-jun Huang
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Consensus ,Allogeneic hematopoietic transplantation ,China ,Indication ,Conditioning regimen ,Donor selection ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.
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- 2021
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14. Investigation of fibrinogen in early bleeding of patients with newly diagnosed acute promyelocytic leukemia
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Tiantian Chu, Hong Wang, Xin Lv, Jiaqian Qi, Yaqiong Tang, Yi Fan, Huiying Qiu, Xiaowen Tang, Chengcheng Fu, Changgeng Ruan, Yue Han, and De-Pei Wu
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acute promyelocytic leukemia ,bleeding ,fibrinogen ,overall survival ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Early hemorrhagic death remains a major cause of treatment failure in acute promyelocytic leukemia (APL). This study investigated the role of fibrinogen concentrations in early hemorrhage and overall survival (OS) of APL patients. Laboratory and clinical data, including fibrinogen concentrations and other coagulation indexes, bleeding events, and survival data, of 198 patients newly diagnosed with APL from February 2012 to December 2017 were extracted from patient records and retrospectively investigated. Patients with moderate/severe bleeding had significantly lower median fibrinogen concentrations (p = .023), higher Chinese disseminated intravascular coagulation scoring system (CDSS) (p 1.6 g/L (p = .015; p = .023). However, moderate/severe (p = .088) and severe bleeding rates (p = .063) were comparable for patients with fibrinogen 12.8 s (p = .005), age ≥60 years (p = .001), and CDSS ≥5 (p = .044) were independent predictors of 1-year OS. Fibrinogen ≤1.6 g/L may be an independent risk factor for early bleeding in newly treated patients with APL and is associated with a worse 1-year OS. Increasing fibrinogen to >1.6 g/L may help to prevent bleeding.
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- 2021
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15. Investigation of the risk factors to predict cytokine release syndrome in relapsed or refractory B-cell acute lymphoblastic leukemia patients receiving IL-6 knocking down anti-CD19 chimeric antigen receptor T-cell therapy
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Wen-Jie Gong, Yan Qiu, Ming-Hao Li, Li-Yun Chen, Yan-Yan Li, Jing-Qiu Yu, Li-Qing Kang, Ai-Ning Sun, De-Pei Wu, Lei Yu, and Sheng-Li Xue
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relapsed or refractory B-cell acute lymphoblastic leukemia ,chimeric antigen receptor T-cell therapy ,cytokine release syndrome ,IL-6 knocking down ,risk factors ,Immunologic diseases. Allergy ,RC581-607 - Abstract
CD19 chimeric antigen receptor-T (CAR-T) cell therapy has achieved remarkable results in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the cytokine release syndrome (CRS) was presented in most patients as common toxicity and severe CRS (sCRS) characterized by the sharp increase in interleukin-6 (IL-6) could be life-threatening. We conducted a phase II clinical trial of ssCAR-T-19 cells, anti-CD19 CAR-T cells with shRNA targeting IL-6, in 61 patients with r/r B-ALL. This trial was registered at www.clinicaltrials.gov as #NCT03275493. Fifty-two patients achieved CR while nine patients were considered NR. The median duration of response (DOR) and overall survival (OS) were not reached (>50 months). CRS developed in 81.97% of patients, including 54.10% with grades 1 to 2 (grade 1, 31.15%; grade 2, 22.95%) and 27.87% with grades 3 to 4 (grade 3, 26.23%; grade 4, 1.64%). sCRS occurs earlier than mild CRS (mCRS). A multivariable analysis of baseline characteristics identified high bone marrow disease burden and poor genetic risk before infusion as independent risk factors for sCRS. After infusion, patients with sCRS exhibited larger expansion of ssCAR-T-19 cells, higher peak levels of IL-6, IL-10, and IFN-γ, and suffered more severe hematological and non-hematological toxicities compared with those with mCRS.
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- 2022
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16. Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study
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Yuan-Kai Shi, Xiao-Nan Hong, Jian-Liang Yang, Wei Xu, Hui-Qiang Huang, Xiu-Bin Xiao, Jun Zhu, Dao-Bin Zhou, Xiao-Hong Han, Jian-Qiu Wu, Ming-Zhi Zhang, Jie Jin, Xiao-Yan Ke, Wei Li, De-Pei Wu, Shen-Miao Yang, Xin Du, Yong-Qian Jia, Ai-Chun Liu, Dai-Hong Liu, Zhi-Xiang Shen, Lian-Sheng Zhang, Leonard James, Edward Hellriegel, and Peng Lyu
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Medicine - Abstract
Abstract. Background:. Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. Methods:. This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. Results:. A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%–81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. Conclusion:. Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. Clinical trial registration:. ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621
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- 2021
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17. Comparable long-term outcomes between upfront haploidentical and identical sibling donor transplant in aplastic anemia: a national registry-based study
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Zheng-Li Xu, Lan-Ping Xu, De-Pei Wu, Shun-Qing Wang, Xi Zhang, Rui Xi, Su-Jun Gao, Ling-Hui Xia, Jian-Min Yang, Ming Jiang, Xin Wang, Qi-Fa Liu, Jia Chen, Ming Zhou, and Xiao-Jun Huang
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for severe aplastic anemia (SAA), and transplantation from identical sibling donors (ISD) has been recommended as a first-line treatment. Haploidentical donor (HID) transplantation for SAA has made great advances; thus, an increased role of HID-SCT in SAA should be considered. We performed a national registry-based analysis comparing long-term outcomes in the upfront HID or upfront ISD SCT setting. A total of 342 SAA patients were enrolled, with 183 patients receiving HID SCT and 159 receiving ISD SCT. The estimated 9-year overall survival and failure-free survival were 87.1±2.5% and 89.3±3.7% (P=0.173) and 86.5±2.6% versus 88.1±3.8% (P=0.257) for patients in the HID and ISD SCT groups, respectively. Transplantation from HID or ISD SCT has greatly improved quality of life (QoL) levels post-HSCT compared to pre-HSCT. The occurrence of chronic graft-versus-host disease was the only identified adverse factor affecting each subscale of QoL. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were all similar between HID and ISD SCT at 5-year time points. At the last follow-up, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. These data suggest that haploidentical transplant can be considered a potential therapeutic option in the upfront setting for SAA patients in the absence of an HLA-identical related or unrelated donor.
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- 2022
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18. Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment
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Zheng Li, Jun Wang, Shuai-Shuai Ge, Qiao-Cheng Qiu, Jia-Hui Du, Shuang-Shuang Shan, Xiang-Dong Shen, Chao-Ling Wan, Bin-Ru Wang, De-Pei Wu, Hui-Ying Qiu, and Sheng-Li Xue
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venetoclax ,azacitidine ,midostaurin ,t(8 ,21) ,relapsed acute myeloid leukemia ,KIT mutation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhibitor. The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy. Our ex vivo study also showed that midostaurin alone could inhibit proliferation and induce apoptosis of Kasumi-1 cells (e.g. Midostaurin induced G2 phase cell arrest, down-regulated p-KIT and BCL-2, while Bax protein levels were up-regulated) and observed a synergistic anti effect when the two drugs were combined. Our study shows that the venetoclax+midostaurin regimen may be a promising treatment option for R/R t(8;21) AML with KIT mutations.
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- 2022
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19. Efficiency of anti‐VEGF therapy in central nervous system AML relapse: A case report and literature review
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Han‐Yu Cao, Tao Tao, Xiang‐Dong Shen, Lian Bai, Chao‐Ling Wan, De‐Pei Wu, Jin‐Li Li, and Sheng‐Li Xue
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AML ,anti‐VEGF therapy ,bevacizumab ,central nervous system (CNS) ,Medicine ,Medicine (General) ,R5-920 - Abstract
Abstract There have been few reports on the treatment of central nervous system (CNS) acute myeloid leukemia (AML) relapse. This case study demonstrates that bevacizumab may be a viable treatment option when combined with IT chemotherapy as maintenance therapy for those with CNS leukemia.
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- 2022
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20. Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report
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Meng-Yun Li, Zhi-Hong Lin, Ming-Ming Hu, Li-Qing Kang, Xiao-xia Wu, Qi-wei Chen, Xin Kong, Jian Zhang, Hui-Ying Qiu, and De-Pei Wu
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CD19 ,Chimeric antigen receptor T cells ,Donor-derived ,Humanized ,Mixed phenotype acute leukemia ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. Case presentation We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. Conclusion This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.
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- 2020
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21. Comparison of haplo-SCT and chemotherapy for young adults with standard-risk Ph-negative acute lymphoblastic leukemia in CR1
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Meng Lv, Qian Jiang, Dao-Bin Zhou, Yu Hu, Dai-Hong Liu, De-Pei Wu, Jing-Bo Wang, Hao Jiang, Jing Wang, Ying-jun Chang, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, and Xiao-Jun Huang
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Haplo-SCT ,Adult chemotherapy ,Ph-negative acute lymphoblastic leukemia ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) as a postremission treatment for standard risk Philadelphia chromosome-negative acute lymphoblastic leukemia (SR Ph-ALL) in the first complete remission (CR1) has not been defined. In this multicenter, phase 3 study (NCT02042690), of the 131 consecutive Ph-ALL young adult patients (YA, aged 18–39 years) without high-risk features who achieved CR1, 114 patients without HLA-matched donors received consolidation with an adult chemotherapy regimen (n = 55) or haplo-SCT (n = 59). In the landmark analysis, haplo-SCT resulted in a lower 2-year cumulative incidence of relapse (CIR, 12.8% vs 46.7%, P = 0.0017) and superior 2-year leukemia-free survival (LFS, 80.9% vs 51.1%, P = 0.0116) and 2-year overall survival (OS, 91.2% vs 75.7 [64.8–93.2] %, P = 0.0408) than chemotherapy. In the time-dependent multivariate analysis with propensity score adjustment, postremission treatment (haplo-SCT vs chemotherapy) was an independent risk factor for the CIR (HR 0.195, 95% CI 0.076–0.499, P = 0.001), LFS (HR 0.297, 95% CI 0.131–0.675, P = 0.003), and OS (HR 0.346, 95% CI 0.140–0.853, P = 0.011). In all subgroups, CIR was lower in haplo-SCT. Myeloablative haplo-SCT with ATG+G-CSF might be one of the preferred therapies for YA patients with standard-risk Ph-ALL. Trial registration ClinicalTrials.gov . Registered on 23 January 2014, https://clinicaltrials.gov/ct2/show/NCT02042690
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- 2020
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22. Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report
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Ze-Fa Liu, Li-Yun Chen, Jin Wang, Li-qing Kang, Hua Tang, Yao Zhou, Hai-Xia Zhou, Ai-Ning Sun, De-Pei Wu, and Sheng-Li Xue
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Acute lymphoblastic leukemia ,Extramedullary relapse ,Chimeric antigen receptor-modified T cell therapy ,IL-6 knocking down ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background Extramedullary relapse is an important cause of treatment failure among patients with acute lymphoblastic leukemia (ALL). This type of relapse is commonly observed in the central nervous system, while it is rare in the testicles and skin. Chimeric antigen receptor-modified T cell (CAR-T) therapy targeting CD19 has shown to be a beneficial treatment approach for relapsed/refractory B cell acute lymphoblasticleukemia (r/r B-ALL). Yet, few studies have reported data regarding the treatment of extramedullary B-ALL relapse, especially both in skin and testicle, with CAR-T therapy. Case presentation Here we reported a single case of a patient with relapsed B-ALL in skin and testicle who was successfully treated by the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy. A 29-year-old man with relapsed B-ALL in skin and testicle was enrolled in clinal trial involving the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy ( ClinicalTrials.gov number, NCT03919240). The patient had toxicity consistent with the grade 1 cytokine release syndrome. Conclusions ssCART-19 therapy may be used to effectively eliminate infiltrating leukemia cells in the skin and testicle with mild toxicity, which could be a much safer approach to bridge allo-HSCT, thus further improving the patient’s outcome. Trial registration ClinicalTrials.gov number, NCT03919240 , Registered 18 April 2019, retrospectively registered.
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- 2020
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23. MYC-regulated lncRNA NEAT1 promotes B cell proliferation and lymphomagenesis via the miR-34b-5p-GLI1 pathway in diffuse large B-cell lymphoma
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Chong-Sheng Qian, Ling-Jie Li, Hai-Wen Huang, Hai-Fei Yang, and De-Pei Wu
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Cell proliferation ,Diffuse large B-cell lymphoma ,GLI1 ,MYC ,LncRNA NEAT1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background LncRNA NEAT1 has been identified as a tumour driver in many human cancers. However, the underlying mechanism of lncRNA NEAT1 in diffuse large B-cell lymphoma (DLBCL) progression is unclear. Methods The expression levels of NEAT1, GLI1 and miR-34b-5p were detected by RT-qPCR and Western blotting in DLBCL tissues and cell lines. MTT and colony formation assays were performed to examine cell proliferation, while annexin-V staining and TUNEL assays were performed to measure cell apoptosis. The effect of NEAT1, GLI1 and miR-34b-5p on cell cycle-associated proteins was evaluated by Western blotting. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were employed to investigate the interaction between NEAT1 and miR-34b-5p or GLI1 and miR-34b-5p. Moreover, chromatin immunoprecipitation (ChIP) was performed to demonstrate the interaction between MYC and NEAT1. Results NEAT1 and GLI1 were upregulated while miR-34b-5p was downregulated in DLBCL tissues and cell lines compared to normal controls. Knockdown of NEAT1 or overexpression of miR-34b-5p inhibited cell proliferation but promoted cell apoptosis. Overexpression of NEAT1 reversed GLI1-knockdown induced attenuation of cell proliferation. In other words, NEAT1 acted as a competing endogenous RNA (ceRNA), regulating the miR-34b-5p-GLI1 axis, further affecting the proliferation of DLBCL. Moreover, MYC modulated NEAT1 transcription by directly binding to the NEAT1 promoter. Conclusion We revealed that MYC-regulated NEAT1 promoted DLBCL proliferation via the miR-34b-5p-GLI1 pathway, which could provide a novel therapeutic target for DLBCL.
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- 2020
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24. A Phase II Trial of the Double Epigenetic Priming Regimen Including Chidamide and Decitabine for Relapsed/Refractory Acute Myeloid Leukemia
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Jia Yin, Chao-Ling Wan, Ling Zhang, Hao Zhang, Lian Bai, Hai-Xia Zhou, Ming-Zhu Xu, Li-Yun Chen, Chong-Sheng Qian, Hui-Ying Qiu, Su-Ning Chen, Xiao-Wen Tang, De-Pei Wu, Yan-Ming Zhang, Ai-Ning Sun, and Sheng-Li Xue
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epigenomics ,histone deacetylase inhibitor (HDACi) ,CDIAG regimen ,relapsed/refractory acute myeloid leukemia ,salvage therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ObjectiveTo explore the role of chidamide, decitabine plus priming regimen in the salvage treatment of relapsed/refractory acute myeloid leukemia.MethodsA clinical trial was conducted in relapsed/refractory acute myeloid leukemia patients using chidamide, decitabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor, termed CDIAG, a double epigenetic priming regimen.ResultsThirty-five patients were recruited. Three patients received 2 treatment cycles. In 32 evaluable patients and 35 treatment courses, the completed remission rate (CRR) was 42.9%. The median OS time was 11.7 months. The median OS times of responders were 18.4 months, while those of nonresponders were 7.4 months (P = 0.015). The presence of RUNX1 mutations was associated with a high CRR but a short 2-year OS (P = 0.023) and PFS (P = 0.018) due to relapse after treatment. The presence of IDH mutations had no effect on the remission rate (80.0% vs. 73.3%), but showed a better OS (2-year OS rate: 100.0% vs. 28.9%). Grade 3/4 nonhematological adverse events included pneumonia, hematosepsis, febrile neutropenia, skin and soft tissue infection and others.ConclusionThe double epigenetic priming regimen (CDIAG regimen) showed considerably good antileukemia activity in these patients. Adverse events were acceptable according to previous experience. The study was registered as a clinical trial.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier:NCT03985007
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- 2021
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25. Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
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Yu Wang, De-Pei Wu, Qi-Fa Liu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Hui Zhang, Wen-Jing Yu, Yang Xu, Fen Huang, and Xiao-Jun Huang
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Anti-thymocyte globulin ,Post-transplant cyclophosphamide ,Low-dose ,Haploidentical ,Graft-versus-host disease ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. Methods We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. Results We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III–IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II–IV acute GVHD (HR 0.58; P = 0.036), grade III–IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P
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- 2019
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26. Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia
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Xin-Yue Zhang, Hai-Ping Dai, Zheng Li, Jia Yin, Xing-Ping Lang, Chun-Xiao Yang, Sheng Xiao, Ming-Qing Zhu, Dan-Dan Liu, Hong Liu, Hong-Jie Shen, De-Pei Wu, and Xiao-Wen Tang
- Subjects
fusion gene ,STRBP-JAK2 ,Ph-like ,chimeric antigen receptor ,B-lymphoblastic leukemia ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Philadelphia chromosome-like B-lymphoblastic leukemia (Ph-like ALL) describes a group of genetically heterogeneous, Ph-negative entities with high relapse rates and poor prognoses. A Janus-kinase-2 (JAK2) rearrangement has been reported in approximately 7% of Ph-like ALL patients whose therapeutic responses to JAK inhibitors have been studied in clinical trials. Here, we report a novel STRBP-JAK2 fusion gene in a 21-year-old woman with Ph-like ALL. Although a normal karyotype was observed, a hitherto unreported JAK2 rearrangement was detected cytogenetically. STRBP-JAK2 fusion was identified by RNA sequencing and validated by Sanger sequencing. The Ph-like ALL proved refractory to traditional induction chemotherapy combined with ruxolitinib. The patient consented to infusion of autologous chimeric antigen receptor (CAR) T cells against both CD19 and CD22, which induced morphologic remission. Haplo-identical stem cell transplantation was then performed; however, she suffered relapse at just one month after transplantation. The patient subsequently received donor lymphocyte infusion after which she achieved and maintained a minimal residual disease negative remission. However, she succumbed to grade IV graft-versus-host disease 7 months post-transplant. In conclusion, this report describes a novel STRBP-JAK2 gene fusion in a Ph-like ALL patient with a very aggressive disease course, which proved resistant to chemotherapy combined with ruxolitinib but sensitive to immunotherapy. Our study suggests that CAR T-cell therapy may be a viable option for this type of leukemia.
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- 2021
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27. Successful application of anti-CD19 CAR-T therapy with IL-6 knocking down to patients with central nervous system B-cell acute lymphocytic leukemia
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Li-Yun Chen, Li-Qing Kang, Hai-Xia Zhou, Han-Qing Gao, Xue-Fei Zhu, Nan Xu, Lei Yu, De-Pei Wu, Sheng-Li Xue, and Ai-Ning Sun
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Few studies have described chimeric antigen receptor–modified T cell (CAR-T) therapy for central nervous system (CNS) B-cell acute lymphocytic leukemia (B-ALL) patients due to life-threatening CAR-T-related encephalopathy (CRES) safety issues. In this study, CAR-Ts targeting CD19 with short hairpin RNA (shRNA)-IL-6 gene silencing technology (ssCART-19s) were prepared. We conducted a phase 1 clinical trial (ClinicalTrials.gov number, NCT03064269). Three patients with relapsed CNS B-ALL were enrolled, conditioned with the fludarabine and cyclophosphamide for lymphocyte depletion and infused with ssCART-19s for three consecutive days. Clinical symptoms and laboratory examinations were monitored. After ssCART-19 treatment, three patients' symptoms resolved almost entirely. Brain leukemic infiltration reduced significantly based on magnetic resonance imaging (MRI), and there were no leukemic blasts in cerebrospinal fluid (CSF), which was confirmed by cytological and molecular examinations. Additionally, increases in the levels of cytokines and immune cells were observed in the CSF of all patients. Only grade 1 cytokine release syndrome (CRS) manifesting as fever was noted in patients. In conclusion, CAR-Ts with shRNA-IL-6 gene knockdown migrated into the CNS, eradicated leukemic cells and elevated cytokines in CSF with mild, acceptable side effects.
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- 2020
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28. Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion
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Hai-Ping Dai, Jia Yin, Zheng Li, Chun-Xiao Yang, Tin Cao, Ping Chen, Yun-Hui Zong, Ming-Qing Zhu, Xia-Ming Zhu, Sheng Xiao, De-Pei Wu, and Xiao-Wen Tang
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NCOR1-LYN ,fusion gene ,dasatinib ,ALL ,pediatric ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in ~10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a member of the ABL/Src-tyrosine kinase family. Somatic LYN rearrangements are found in 5 cases of hematopoietic malignancies so far, although none of them were treated with tyrosine kinase inhibitors.Case presentation: A 6-year-old boy with relapsed B-ALL had no response to reinduction chemotherapy. He was then treated with the ABL1 tyrosine kinase inhibitor dasatinib and achieved complete remission within 2 weeks. Haploidentical allogenic stem cell transplantation (allo-HSCT) was subsequently performed and maintenance therapy with dasatinib initiated 8 weeks post-transplantation. He has been in minimal residual disease negative remission for 10 months after allo-HSCT.Result: His bone marrow karyotype showed a balanced translocation between chromosomes 8 and 17, leading to a NCOR1-LYN fusion gene confirmed with sequencing.Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion.
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- 2020
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29. MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death
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Chao Ding, Su-Ning Chen, Roderick A. F. Macleod, Hans G. Drexler, Stefan Nagel, De-Pei Wu, Ai-Ning Sun, and Hai-Ping Dai
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Acute myeloid leukemia ,miR-130a ,t(8 ,21) ,outcome ,overexpression ,Medicine - Abstract
Background: Emerging evidence has revealed that miRNAs can function as oncogenes or tumor suppressor genes in leukemia. The ectopic expression of miR-130a has been reported in chronic leukemia, but our understanding of the biological implications of miR-130a expression remains incomplete. Methods: We quantified a cohort of de novo acute myeloid leukemia (AML) by bead-based miRNA and real-time quantitative PCR (Rq-PCR). The luciferase reporter gene assay was analyzed after the plasmid constructs which contain 5’-UTR of miR-130a and a Renilla luciferase reporter plasmid were transfected simultaneously into 293T cells. MTT and caspase 3/7 apoptosis assays were used to test cell viability and apoptosis. Results: We identified miR-130a as significantly overexpressed in t(8;21) AML. Expression of miR-130a decreased significantly once patients with t(8;21) achieved complete remission, but increased sharply at the time of relapse. In patients with t(8;21) AML, KIT mutational status was associated with miR-130a expression—with higher expression associated with KIT activating mutations. Increased miR-130a expression in t(8;21) AML was associated with slightly worse event-free survival; however, no impact on overall survival was observed. Knockdown of AML1/ETO protein in the SKNO-1 cell line resulted in decrease of expression of miR-130a. Direct binding of AML1/ETO fusion protein with the promoter sequence of miR-130a was detected with luciferase reporter gene assay. Following miR-130a knockdown, SKNO-1 demonstrated increased sensitivity to etoposide. Conclusions: Our data suggest that miR-130a is directly activated by AML1/ETO, and may act as a factor which is associated with leukemia burden, event-free survival, and chemotherapy sensitivity in t(8;21) AML.
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- 2018
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30. Pyrosequencing quantified methylation level of miR-124 predicts shorter survival for patients with myelodysplastic syndrome
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Hong Wang, Tong-Tong Zhang, Song Jin, Hong Liu, Xiang Zhang, Chang-Geng Ruan, De-Pei Wu, Yue Han, and Xiao-Qin Wang
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miR-124 ,Methylation ,MDS ,Prognosis ,Pyrosequencing ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Aberrant CpG island methylation has been increasingly recognized as a common event in myelodysplastic syndrome (MDS). To date, most of the previous studies of miR-124 in MDS have focused on epigenetic changes and little is known about the underlying mechanism through which miR-124 regulates CDK6 expression. Results In the present study, we employed pyrosequencing analysis to quantify the methylation levels of upstream regions of the miR-124 genes (miR-124-1, miR-124-2 and miR-124-3) in 56 primary MDS patients. We found the three miR-124 genes were methylated in MDS patients. Univariate analysis revealed that the World Health Organization (WHO) classification, marrow blast count, karyotype, International Prognostic Scoring System (IPSS), mean corpuscular volume, as well as high methylation of miR-124-1, miR-124-2 and miR-124-3 were significantly related to overall survival. In leukaemia-free survival, patients who were older and had an advanced WHO classification, high marrow blast counts, high IPSS risk and high methylation of miR-124-1 and miR-124-2 progressed rapidly to acute myeloid leukaemia. Multivariate analysis demonstrated that high methylation of miR-124-3 was an independent factor of overall survival. Median survival of patients with high miR-124-3 methylation was significantly shorter (7.6 months) than patients with low methylation (32.7 months; P = 0.010). A functional study revealed that silencing of miR-124 resulted in upregulation of its target gene, cyclin dependent kinase CDK6, which in turn promoted cell proliferation in the MDS cell line SKM-1. Conclusions High methylation of miR-124-3 predicts shorter survival for patients with MDS, which may be a useful prognostic marker in MDS.
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- 2017
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31. Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant
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Lan-Ping Xu, Song Jin, Shun-Qing Wang, Ling-Hui Xia, Hai Bai, Su-Jun Gao, Qi-Fa Liu, Jian-Min Wang, Xin Wang, Ming Jiang, Xi Zhang, De-Pei Wu, and Xiao-Jun Huang
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Upfront ,Haploidentical transplantation ,Acquired severe aplastic anemia ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients. Methods We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled. Results Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9–20) and 11 (range, 8–19) days, with a cumulative incidence of 97.8 and 97.1% (P = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II–IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P
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- 2017
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32. Impact of FLT3-ITD length on prognosis of acute myeloid leukemia
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Song-Bai Liu, Hao-Jie Dong, Xie-Bing Bao, Qiao-Cheng Qiu, Hong-Zhi Li, Hong-Jie Shen, Zi-Xuan Ding, Chao Wang, Xiao-Ling Chu, Jing-Qiu Yu, Tao Tao, Zheng Li, Xiao-Wen Tang, Su-Ning Chen, De-Pei Wu, Ling Li, and Sheng-Li Xue
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2019
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33. Use of combination therapy to successfully treat breakthrough Trichosporon asahii infection in an acute leukemia patient receiving voriconazole
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Jia Chen, Feng Chen, Ying Wang, Ling-Yi Yang, Miao Miao, Yue Han, and De-Pei Wu
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T. asahii ,Liposomal amphotericin B ,Caspofungin ,Voriconazole ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Trichosporon species is an important life-threatening opportunistic systemic pathogen, especially in leukemia patients. Voriconazole is proved to be a promising agent in past decade. However, recently we observed a case of breakthrough Trichosporon asahii infection while receiving voriconazole, which calls for an alternative treatment strategy. A combination therapy of liposomal amphotericin B (AmB) plus caspofungin – in which liposomal AmB dose was reduced due to renal toxicity – was administered to successfully treat this patient.
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- 2014
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34. A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities
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Sheng-Li Xue, Jin-Li Li, Jing-Ying Zou, Jian Su, Su-Ning Chen, and De-Pei Wu
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2012
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35. A model based on machine learning for the prediction of cyclosporin A trough concentration in Chinese allo-HSCT patients
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Lin Song, Chen-Rong Huang, Shi-Zheng Pan, Jian-Guo Zhu, Zong-Qi Cheng, Xun Yu, Ling Xue, Fan Xia, Jin-Yuan Zhang, De-Pei Wu, and Li-Yan Miao
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Pharmacology (medical) ,General Medicine ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
Cyclosporin A is a calcineurin inhibitor which has a narrow therapeutic window and high interindividual variability. Various population pharmacokinetic models have been reported; however, professional software and technical personnel were needed and the variables of the models were limited. Therefore, the aim of this study was to establish a model based on machine learning to predict CsA trough concentrations in Chinese allo-HSCT patients. A total of 7874 cases of CsA therapeutic drug monitoring data from 2069 allo-HSCT patients were retrospectively included. Sequential forward selection was used to select variable subsets, and eight different algorithms were applied to establish the prediction model. XGBoost exhibited the highest prediction ability. Except for the variables that were identified by previous studies, some rarely reported variables were found, such as norethindrone, WBC, PAB, and hCRP. The prediction accuracy within ±30% of the actual trough concentration was above 0.80, and the predictive ability of the models was demonstrated to be effective in external validation. In this study, models based on machine learning technology were established to predict CsA levels 3–4 days in advance during the early inpatient phase after HSCT. A new perspective for CsA clinical application is provided.
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- 2022
36. Mutation spectrum of <scp>FLT3</scp> and significance of non‐canonical <scp>FLT3</scp> mutations in haematological malignancy
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Shuai‐Shuai Ge, Qiao‐Cheng Qiu, Hai‐Ping Dai, Xiang‐Dong Shen, Tian‐Mei Wu, Jia‐Hui Du, Chao‐Ling Wan, Hong‐Jie Shen, De‐Pei Wu, Sheng‐Li Xue, and Song‐Bai Liu
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Hematology - Published
- 2023
37. Switching from Eltrombopag to Hetrombopag in Patients with Primary Immune Thrombocytopenia (ITP): Post-Hoc Analysis of a Multicenter, Randomized Phase III Trial
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Yu Hu, Renchi Yang, Ting Niu, Heng Mei, Liu Xiaofan, Yan Li, Hu Zhou, Ying Feng, Guangxun Gao, Peng Cheng, Ruibin Huang, Linhua Yang, Jianda Hu, Ming Hou, Yazhou Yao, Li Liu, Yi Wang, De-Pei Wu, Xuliang Shen, Jie Jin, Jianmin Luo, Zeng Yun, Xin Zhou, Ruixiang Xiang, Zhongxing Jiang, Yuansong Bai, Junye Xiong, Runzi Li, and Jianjun Zou
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
38. Long-term follow-up of haploidentical transplantation in relapsed/refractory severe aplastic anemia: a multicenter prospective study
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Lan-Ping, Xu, Zheng-Li, Xu, Shun-Qing, Wang, De-Pei, Wu, Su-Jun, Gao, Jian-Min, Yang, Ling-Hui, Xia, Qi-Fa, Liu, Ming, Jiang, Hai, Bai, Xi, Zhang, Xin, Wang, and Xiao-Jun, Huang
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Adult ,Multidisciplinary ,Adolescent ,Transplantation, Haploidentical ,Quality of Life ,Humans ,Anemia, Aplastic ,Graft vs Host Disease ,Prospective Studies ,Child ,Follow-Up Studies - Abstract
In recent decades, haploidentical stem cell transplantation (haplo-SCT) to treat severe aplastic anemia (SAA) has achieved remarkable progress. However, long-term results are still lacking. We conducted a multicenter prospective study involving SAA patients who underwent haplo-SCT as salvage therapy. Long-term outcomes were assessed, mainly focusing on survival and quality of life (QoL). Longitudinal QoL was prospectively evaluated during pretransplantation and at 3 and 5 years posttransplantation using the SF-36 scale in adults and the PedsQL 4.0 scale in children. A total of 287 SAA patients were enrolled, and the median follow-up was 4.56 years (range, 3.01-9.05 years) among surviving patients. During the long-term follow-up, 268 of 275 evaluable patients (97.5%) obtained sustained full donor chimerism, and 93.4% had complete hematopoietic recovery. The estimated overall survival and failure-free survival for the whole cohort at 9 years were 85.4% ± 2.1% and 84.0% ± 2.2%, respectively. Age (≥18 years) and a poorer performance status (ECOG 1) were identified as risk factors for survival outcomes. For QoL recovery after haplo-SCT, we found that QoL progressively improved from pretransplantation to the 3-year and 5-year time points with statistical significance. The occurrence of chronic graft versus host disease was a risk factor predicting poorer QoL scores in both the child and adult cohorts. At the last follow-up, 74.0% of children and 72.9% of adults returned to normal school or work. These inspiring long-term outcomes suggest that salvage transplantation with haploidentical donors can be routine practice for SAA patients without human leukocyte antigen (HLA)-matched donors.
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- 2022
39. Data from Haploidentical versus Matched-Sibling Transplant in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia: A Biologically Phase III Randomized Study
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Xiao-Jun Huang, De-Pei Wu, Mei-Qing Wu, Xiao Ma, Xiao-Hui Zhang, Kai-Yan Liu, Lan-Ping Xu, Qi-Fa Liu, and Yu Wang
- Abstract
Purpose: Although matched-sibling donor (MSD) hematopoietic stem-cell transplantation (HSCT) has an established role in the management of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1), the effect of haploidentical donor (HID) HSCT as post-remission treatment for this portion of patients is not defined.Experimental Design: Transplantation outcomes from HIDs or MSDs were compared in a disease-specific, biologically phase III randomized, multicenter study. Between July 2010 and December 2013, 210 patients with Philadelphia-negative high-risk ALL in CR1 were assigned to undergo unmanipulated HIDs (121 patients) or MSDs HSCT (89 patients) according to donor availability on an intent-to-treat (ITT) basis.Results: Overall, 24 of the 210 patients had lost transplant eligibility. Therefore, 186 of 210 (88%) patients were finally transplanted from MSD (n = 83) or HID (n = 103). Based on the ITT principle, the 3-year disease-free survival (DFS) did not differ between HID and MSD groups [61%, 95% confidence interval (CI), 52%–70%; vs. 60%, CI, 49%–71%; P = 0.91] from CR, neither did DFS differ between the two groups (68%, CI, 58%–78%; vs. 64%, CI, 52%–76%; P = 0.56) from time of the graft, with cumulative incidence of nonrelapse mortality of 13% (CI, 7%–19%) and 11% (CI, 4%–18%; P = 0.84) and relapse rates of 18% (CI, 10%–26%) and 24% (CI, 14%–34%; P = 0.30), respectively.Conclusions: Haploidentical HSCT achieves outcomes similar to those of MSD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation could be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor. Clin Cancer Res; 22(14); 3467–76. ©2016 AACR.
- Published
- 2023
40. Anti-CD19 CAR T-Cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia
- Author
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Liyun Chen, Wen-Jie Gong, Ming-Hao Li, Hai-Xia Zhou, Ming-Zhu Xu, Chong-Sheng Qian, Li-Qing Kang, Nan Xu, Zhou Yu, Man Qiao, Tong-Tong Zhang, Ling Zhang, Zheng-Long Tian, Ai-Ning Sun, Lei Yu, De-Pei Wu, and Sheng-Li Xue
- Subjects
Hematology - Abstract
We conducted a single-arm, open-label, single-center phase I study (Clinicaltrials.gov NCT03984968) to assess the safety and efficacy of multicycle-sequential anti-CD19 CAR T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and TKI as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-ALL who are not eligible for allo-HSCT. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another three cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at three different doses: (2×106/kg, 3.25×106/kg, and 5×106/kg). The phase I results of the first 15 patients, including 2 withdrawals, are presented. Phase II research is still ongoing. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There were no CRS above grade 2 or ICANS, or grade 4 nonhematologic toxicities. All 13 patients achieved CR, including 12 patients with CMR at the data cutoff on Mar 31, 2022. The RFS was 84% (95% CI, 66%-100%), and the OS was 83% (95% CI, 58%-100%) with a median follow-up of 27 months (7-57 months). The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings merit further evaluation and could form the basis for the development of an allo-HSCT-free consolidation paradigm.
- Published
- 2023
41. [Comparison of Therapeutic Efficacy between Hypomenthylating Agents Combined with Venetoclax and Half Dose Priming Regimen in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia]
- Author
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Ming-Zhu, Xu, Man, Qiao, Ai-Ning, Sun, De-Pei, Wu, Sheng-Li, Xue, and Hai-Xia, Zhou
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Leukemia, Myeloid, Acute ,Humans ,Aged ,Retrospective Studies - Abstract
To compare the clinical efficacy and safety of hypomenthylating agents (HMA) combined with Venetoclax (VEN) and half dose priming regimen (CAG-like) in the treatment of elderly patients with newly diagnosed acute myeloid leukemia (AML) who were not suitable for intensive chemotherapy.The clinical data of 43 newly diagnosed elderly patients with AML who were not suitable for intensive chemotherapy in our hospital from April 2019 to October 2020 were retrospectively analyzed. Among them, 16 cases received HMA-VEN regimen and 27 cases received HMA-CAG-like regimen. The remission rate, early mortality and survival were compared between the two groups. And, the patients were grouped according to HCT-CI score. The effects of two different regimens in different groups on the efficacy and survival of patients were compared, and the prognosis of patients was further analyzed.After one course of treatment, the total remission rate of HMA-VEN group and HMA-CAG-like group was 81.3% (13/16) and 51.9% (14/27), respectively, and the difference between the two groups was statistically significant (χ2=4.650,Venetoclax combined with HMA can achieve higher response rate, lower early mortality, and longer OS, especially in those with more comorbidities and poor tolerability.去甲基化药物联合Venetoclax与半量预激类方案治疗老年初诊急性髓系白血病的疗效比较.比较去甲基化药物(HMA)联合Venetoclax(VEN)方案与HMA联合半量预激类(CAG-like)方案治疗不适合接受强化疗的老年初诊急性髓系白血病患者的临床疗效及安全性.回顾性分析苏州大学附属第一医院2019年4月至2020年10月43例初诊不适合接受强化疗的老年急性髓系白血病患者的临床资料,16例接受HMA-VEN方案治疗,27例接受HMA-CAG-like方案治疗。比较两组患者的缓解率、早期死亡率及生存情况,并根据HCT-CI评分分组,比较不同分组中两种不同方案对患者疗效及生存的影响,进一步对患者预后进行分析.治疗1个疗程后,HMA-VEN组和HMA-CAG-like组的总缓解率分别为81.3%(13/16)和51.9%(14/27),比较差异具有统计学意义(χ2=4.650,Venetoclax联合HMA能够获得更高的治疗反应率、更低的早期死亡率以及更长的总生存期,尤其是在患者合并症多、耐受性差的情况之下.
- Published
- 2022
42. Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia
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Wen-Yan Cheng, Jian-Feng Li, Yong-Mei Zhu, Xiang-Jie Lin, Li-Jun Wen, Fan Zhang, Yu-Liang Zhang, Ming Zhao, Hai Fang, Sheng-Yue Wang, Xiao-Jing Lin, Niu Qiao, Wei Yin, Jia-Nan Zhang, Yu-Ting Dai, Lu Jiang, Xiao-Jian Sun, Yi Xu, Tong-Tong Zhang, Su-Ning Chen, Hong-Hu Zhu, Zhu Chen, Jie Jin, De-Pei Wu, Yang Shen, and Sai-Juan Chen
- Subjects
Leukemia, Myeloid, Acute ,Multidisciplinary ,Myelodysplastic Syndromes ,Humans ,Cell Differentiation ,Transcriptome ,Hematopoietic Stem Cells - Abstract
The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1–G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6–G8, showing high expression of HOXA / B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX -primitive (G7) , HOX -mixed (G8), and HOX -committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.
- Published
- 2022
43. Integrative genomic and transcriptomic profiling reveals distinct molecular subsets in adult mixed phenotype acute leukemia
- Author
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Qian Wang, Wen‐zhi Cai, Qin‐rong Wang, Ming‐qing Zhu, Ling‐zhi Yan, Yan Yu, Xie‐bing Bao, Hong‐jie Shen, Hong Yao, Jun‐dan Xie, Tong‐tong Zhang, Ling Zhang, Xiao‐yu Xu, Zhe Shan, Hong Liu, Jian‐nong Cen, Dan‐dan Liu, Jin‐lan Pan, Da‐ru Lu, Jia Chen, Yang Xu, Ri Zhang, Ying Wang, Sheng‐li Xue, Miao Miao, Yue Han, Xiao‐wen Tang, Hui‐ying Qiu, Ai‐ning Sun, Jin‐yan Huang, Hai‐ping Dai, De‐pei Wu, and Su‐ning Chen
- Subjects
Hematology - Abstract
Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL.
- Published
- 2022
44. Tandem CD19/CD22 CAR-T cells conquer high-risk cytogenetics and acquire complete remission in r/r B-ALL patients
- Author
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Wei Cui, Xin-Yue Zhang, Hai-Ping Dai, Jia Yin, Zheng Li, Qing-Ya Cui, Li-Qing Kang, Lei Yu, De-Pei Wu, and Xiao-Wen Tang
- Abstract
Background CD19 chimeric antigen receptor T cells (CAR-T cells) have demonstrated impressive response rates in relapse and refractory B acute lymphoblastic leukemia (r/r B-ALL). However, a high rate of patients suffered a CD19-negative (CD19−) relapse, and confers dismal outcomes. Dual targets approaches are proved to optimize the response rate and prevent antigen negative relapse. While for r/r B-ALL patients, whether it would show better outcome than CD19 CAR-T, is still not clear. Methods We conducted an open label, single center clinical trial at the First Affiliated Hospital of Soochow University to investigate the efficacy and safety of tandem CD19/CD22 dual targets CAR-T cells for r/r B-ALL. Results A total of 47 r/r B-ALL patients with high-risk cytogenetics, such as TP53 alteration, Philadelphia Chromosome positive (Ph+) ALL with T315I mutation and Ph-like ALL, received CD19/CD22 CAR-T therapy from 2017 October to 2021 June. Severe cytokine release syndrome occurred in 8 of 47 patients (17.02%). The immune effector cell-associated neurotoxicity syndrome (ICANS) and macrophage release syndrome (MAS) were rare observed. Hematologic complete remission (CR) was observed in 47/47 (100%) and 40/47 (85.1%) patients achieved minimal residual disease negative (MRD-) CR. At a median follow up of 24.83 months (range, 2.57 to 50.67), overall survival was 93.56% (95% CI, 81.36–97.8%) at 6 months, 80.51% (95% CI, 65.88–89.35%) at 1 year. Twelve patients relapsed post CAR-T infusion and only 2 of 12 had CD19- recurrence. The leukemia free survival (LFS) rate and cumulative incidence of relapse at 1 year was 74.47% (95% CI, 59.44–84.61%) and 19.66% (95% CI, 4.36–42.68%), respectively. High-risk cytogenetics did not affect the long long-term survival. The multivariable Cox regression analyses showed that better long-term LFS was associated with MRD-CR status post CAR-T, as well as bridging hematopoietic stem cell transplantation (HSCT). Conclusions Tandem CD19/CD22 CAR-T cells are safety and effective for patients with high-risk cytogenetics. Allo-HSCT can provide long-term durable disease control in these patients. Trial Registration: ClinicalTrials.gov identifier: NCT 03614858
- Published
- 2022
45. Bifunctional effect of the inflammatory cytokine tumor necrosis factor α on megakaryopoiesis and platelet production
- Author
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Tiantian Chu, Shuhong Hu, Jiaqian Qi, Xueqian Li, Xiang Zhang, Yaqiong Tang, Meng Yang, Yang Xu, Chang‐Geng Ruan, Yue Han, and De‐Pei Wu
- Subjects
Blood Platelets ,Mice ,Tumor Necrosis Factor-alpha ,Animals ,Humans ,Cytokines ,Hematology ,Megakaryocytes ,Thrombopoiesis - Abstract
Platelets are affected by many factors, such as infectious or aseptic inflammation, and different inflammatory states may induce either thrombocytopenia or thrombocytosis. Tumor necrosis factor α (TNFα) is an important inflammatory cytokine that has been shown to affect the activity of hematopoietic stem cells. However, its role in megakaryocyte (MK) development and platelet production remains largely unknown. This study aimed to investigate the effects of TNFα on MK and platelet generation.The ex vivo study with human CD34Our study revealed distinct roles for TNFα in megakaryopoiesis and thrombopoiesis and may provide new insights regarding the treatment for platelet disorders.
- Published
- 2022
46. [Observation of Nutritional Status Changes in Patients with Acute Leukemia During Chemotherapy]
- Author
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Li-Ling, Zong, Jing, Yang, Sheng-Li, Xue, De-Pei, Wu, Xia-Ming, Zhu, Yong-Qin, Ge, and Qiao-Cheng, Qiu
- Subjects
Leukemia, Myeloid, Acute ,Nutrition Assessment ,Acute Disease ,Humans ,Nutritional Status ,Induction Chemotherapy ,Precursor Cell Lymphoblastic Leukemia-Lymphoma - Abstract
To assess changes of nutritional status by comprehensive nutrition assessment including nutritional risk screening, dietary assessment, blood biochemical index, and body composition in acute leukemia patients who had undergone chemotherapy.A total of 169 patients with acute leukemia treated at The First Affiliated Hospital of Soochow University from June 2018 to August 2019 were recruited for this study. Before and after chemotherapy, the NRS-2002 and PG-SGA scales, dietary intake, blood biochemical index and body composition were evaluated to compare the changes of nutritional status.NRS-2002 score and PG-SGA score after chemotherapy were significantly increased than those before chemotherapy (P0.001). Many patients had insufficient nutritional intake during chemotherapy, and the dietary intake score of patients with induction chemotherapy was significantly lower than that of patients with consolidation chemotherapy (P=0.043). The results of multivariate analysis showed that induction chemotherapy was the independent risk factor for the increase of PG-SGA scores and the decrease of dietary intake (all P0.05). After chemotherapy, the white blood cell count, hemoglobin, and platelet count were significantly decreased (P0.001), the prealbumin was significantly increased (P0.001), and the blood glucose was increased (P=0.04), but albumin was not significantly changed. The weight, body mass index, fat-free mass, skeletal muscle mass and intracellular water were all significantly decreased (P0.001), and visceral fat area was increased significantly after chemotherapy (P0.05), especially in newly-diagnosed acute lymphoblastic leukemia patients after the induction of chemotherapy.The nutritional status of patients with acute leukemia has undergone significant changes after chemotherapy. A single indicator has limited significance for nutritional status assessment. Comprehensive assessment of nutritional status by multiple tools is worthy of clinical application.急性白血病患者化疗期间营养状况变化的观察研究.针对接受诱导及巩固化疗的急性白血病患者进行包含营养风险筛查、膳食评价、血生化指标监测、人体成分分析的综合营养评估,分析化疗期间营养状况变化。.纳入2018年6月至2019年8月于苏州大学附属第一医院就诊的169例急性白血病患者,化疗前后分别进行NRS-2002及PG-SGA量表评估,评估化疗过程中膳食摄入量,测定患者血常规、血生化指标,监测人体成分,从多个维度比较化疗前后营养状况的变化。.化疗后患者NRS-2002评分、PG-SGA评分较化疗前明显升高(P0.001);化疗期间许多患者存在营养摄入不足情况,初治化疗患者膳食摄入评分明显低于巩固化疗患者(P=0.043);多因素分析结果显示,初治诱导化疗为患者PG-SGA评分升高、膳食摄入减少的独立危险因素( 均P0.05);患者接受化疗后,白细胞计数、血红蛋白、血小板计数较化疗前明显下降(P0.001),前白蛋白明显升高(P0.001),血糖升高(P=0.04),白蛋白水平改变不明显;患者化疗后体重、身体质量指数、去脂体重、骨骼肌质量、细胞内水分均明显下降(P0.001),内脏脂肪面积明显升高(P0.05)。这一变化在初治急性淋系白血病患者中更明显。.急性白血病患者化疗后营养状况发生了明显变化,单一指标对营养状态评估意义有限,多种工具综合评估营养状况值得在临床中推广应用。.
- Published
- 2022
47. Safety and Efficacy of CD22 and CD19 Chimeric Antigen Receptor T Cell Treatment Bridging to Autologous Stem Cell Transplantation As Consolidation Therapy for B-Cell Acute Lymphoblastic Leukemia
- Author
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Yan Qiu, Chong-Sheng Qian, Hai-Xia Zhou, Ming-Zhu Xu, Li-Qing Kang, Ai-Ning Sun, De-Pei Wu, Lei Yu, and Shengli Xue
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
48. Rapid and deep response to avapritinib in heavily treated acute myeloid leukemia with t (8;21) and KIT mutation
- Author
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Jia Yin, Feng Zhu, Zhi-Bo Zhang, Qian Wang, Xue-Feng He, Qian Wu, Jing-Ren Zhang, Ai-Ning Sun, De-Pei Wu, Xiao-Fei Yang, and Su-Ning Chen
- Subjects
Leukemia, Myeloid, Acute ,Proto-Oncogene Proteins c-kit ,Triazines ,Mutation ,Humans ,Pyrazoles ,Pyrroles ,Hematology ,General Medicine - Published
- 2022
49. [Effects of Leukapheresis on Hemostatic Function in Patients with Hyperleukocytic Leukemia]
- Author
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Yu-Qing, Tu, Yi, Fan, Tie-Mei, Song, Zi-Ling, Zhu, Yu-Feng, Feng, Li-Jun, Dai, Hui-Rong, Chang, and De-Pei, Wu
- Subjects
Leukemia, Myeloid, Acute ,Acute Disease ,Humans ,Hemorrhage ,Blood Coagulation Tests ,Leukapheresis ,Blood Coagulation ,Hemostatics - Abstract
To analyze and compare the effects of leukapheresis on hemostatic function in patients with hyperleukocytic leukemia.A total of 139 patients with AML, ALL and CML who underwent leukapheresis from June 2009 to February 2020 and did coagulation test before and after operation were included in this study. The clearance efficiency of each group and the difference among three groups were evaluated, as well as hemostatic function including platelet counts, coagulation indicators, CDSS score and incidence of adverse events. The difference of hemostatic function caused by leukapheresis in different leukemia patients were compared.After leukapheresis, the WBC counts were decreased significantly in the three groups of patients (P0.001), and the clearance efficiency was highest in ALL patients. However, the platelet counts also were decreased significantly (AML:P<0.001, ALL: P<0.001, CML: P<0.01) in the three groups of patients, particularly for acute leukemia patients with a positive correlation with WBC clearance efficiency(r=0.284). After leukapheresis, fibrinogen decreased, PT and APTT prolonged. For acute leukemia patients, higher CDSS score was related to an elevated incidence of bleeding events (P0.05).Leukapheresis is an effective method to decrease the leukemic burden, but it is necessary to monitor the impact on hemostatic function. It is recommended to assess the CDSS socre for acute leukemia patients, in order to identify the predictive value for bleedings.白细胞清除术对高白细胞性白血病患者止血功能的影响.分析比较不同高白细胞性白血病患者进行白细胞清除对止血功能的影响.本研究纳入了2009年6月至2020年2月共139例行白细胞清除术且术前术后进行凝血指标检测的AML、ALL和CML患者,评估各组的清除效果和组间清除效率的差异,并通过血小板、凝血指标的变化、CDSS评分、不良事件发生率的计算,比较该技术在不同白血病患者中导致的止血功能差异.三类患者白细胞清除术后,白细胞数均显著下降(P<0.001),以ALL患者清除效果最佳。白细胞清除术后患者的血小板数均显著下降(AML:P<0.001, ALL: P<0.001, CML: P<0.01),其中急性白血病患者的血小板下降风险更高,且下降幅度与白细胞清除效率呈正相关(r=0.284)。此外,清除术后患者纤维蛋白原降低,凝血酶原时间和活化部分凝血活酶时间均延长。急性白血病患者中,清除后CDSS评分较高的患者出血事件概率更高(P<0.05).白细胞清除术是高白细胞性白血病患者降低肿瘤负荷的有效手段,但仍需警惕其对止血功能的影响,急性白血病患者建议进行CDSS评分,以进一步明确其对出血事件预测意义.
- Published
- 2022
50. [The Role of Whole Body DWI in the Evaluation of Bone Disease in Multiple Myeloma]
- Author
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Yan, Xie, You-You, Hui, Fei-Rong, Yao, Chun-Hong, Hu, Ling-Zhi, Yan, De-Pei, Wu, and Cheng-Cheng, Fu
- Subjects
Diffusion Magnetic Resonance Imaging ,Humans ,Whole Body Imaging ,Bone Diseases ,Multiple Myeloma ,Retrospective Studies - Abstract
To explore the characteristics of ADC value changes in DWI of newly diagnosed symptomatic MM patients and its correlation with R-ISS stage.The data of 148 newly diagnosed symptomatic MM patients treated by whole-body DWI scan at The First Affiliated Hospital of Soochow University from June 2016 to June 2019 were selected and retrospectively analyzed and 30 cases of age-matched healthy people were selected as controls. The differences of ADC values between the patients in normal control group, DWIThe plasma cell percentage of the patients in DWIDWI全身DWI在多发性骨髓瘤骨病评估中的作用.探讨初诊症状性多发性骨髓瘤(MM)患者DWI检查的ADC值变化特征及其与R-ISS分期的相关性.回顾性分析2016年6月至2019年6月于苏州大学附属第一医院接受全身DWI检查的初诊症状性MM患者148例的资料,另选取年龄匹配的健康人30例作为对照,比较正常对照、DWIDWIMM患者DWI
- Published
- 2022
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