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Higher CD34+ cell dose and rapid natural killer cell recovery improve clinical outcome after transplantation in patients with myeloid malignancies

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Higher CD34+ cell dose and rapid natural killer cell recover...

真菌感染标志物结合影像学证据在恶性血液病侵袭性真菌感染早期诊断中的价值

第十四届全国免疫学学术大会

作者： Fei Zhao erlie jiang 中国医学科学院血液病医院

Objective:The CD34cells dose in graft as well as early immune reconstitution are essential for the graft-vs-leukemia(GVL) effect to eliminate residual leukemia cells after allogeneic hematopoietic stem cell transplantation(allo-HSCT).This study is to elucidate the impact of CD34cell dose in graft on immune reconstitution and clinical outcomes after ***:This study retrospectively analyzed 180 myeloid malignancies patients who received allo-HSCT between June2012 and May *** characterized NK cell in day30 after transplantation(NK30) in recipients with multicolor *** patients were divided into high-and low-CD34 groups or high-and low-NK30 group at the cutoff value of4.5×10/kg and 150/ul,*** cumulative incidence of relapse(CIR) was assessed using competing risks from the time of HSCT to death or ***:Total 180 patients were enrolled,including 36 high-CD34 group and 144 low-CD34 *** median follow-up time was 45.1(1.9-1 07.5) *** dose of CD34cells in graft correlated significantly with NK30(Pearson R2=0.55,P<0.001), while there was no correlation to the transplanted dose of NK cells(Pearson R2=0.0002,P=0.84).Meanwhile,the high-CD34 group and high-NK30 group showed better 3-year relapse-free survival(RFS)(88.9±5.2% vs 65.1±4.0%,P=0.003;85.9±4.3% vs 59.2±4.6%,P<0.001) and overall survival(OS)(88.9±5.2% vs 71.3±3.8%,P=0.005;87.5±4.1% vs70.5±4.3%,P=0.003) than did control group,without any increase in graft-versus-host disease(GVHD).Multivariate analysis revealed that the high-CD34 group and high-NK30 group was associated with higher RFS(hazard ratio [HR]4.45,P=0.004;HR,3.75,P<0.001),OS(HR,3.27;P=0.024;HR,2.91,P=0.006),and lower CIR(HR,6.76,P=0.009;HR,8.88,P<0.001).Conclusion:Higher CD34cell dose in graft was beneficial to early NK reconstitution to support the enhanced GVL effect in patients with myeloid malignancies after transplantation.

关键词： allo-HSCT NK CD34+ Relapse-free survival

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中华内科杂志 2020年第10期59卷 751-753页

作者：姜尔烈韩明哲中国医学科学院血液病医院(中国医学科学院血液学研究所) 天津300020

侵袭性真菌病(IFD)是造血干细胞移植后受者感染死亡的主要原因,以侵袭性肺曲霉菌病(IPA)对患者的危害最大。早期确诊病原菌并开始治疗对于降低发病率和病死率至关重要。目前的诊断技术手段存在不足。本次修订版参照国际相关的诊断和管... 详细信息

侵袭性真菌病(IFD)是造血干细胞移植后受者感染死亡的主要原因,以侵袭性肺曲霉菌病(IPA)对患者的危害最大。早期确诊病原菌并开始治疗对于降低发病率和病死率至关重要。目前的诊断技术手段存在不足。本次修订版参照国际相关的诊断和管理指南,对我国原有的IFD诊断标准与治疗原则进行了再次修订。

关键词：血液病恶性肿瘤侵袭性真菌病

髓系恶性肿瘤异基因造血干细胞移植后的维持治疗

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白血病．淋巴瘤 2023年第8期32卷 505-509页

作者：郑欣慧姜尔烈中国医学科学院血液病医院(中国医学科学院血液学研究所)实验血液学国家重点实验室、国家血液系统疾病临床医学研究中心、细胞生态海河实验室天津300020

急性髓系白血病和骨髓增生异常综合征是常见的髓系恶性肿瘤, 异基因造血干细胞移植是其治愈的主要手段之一, 但对于高危患者, 复发率可超过40%, 移植后复发患者预后极差, 因此移植后预防复发至关重要。移植后血液学、分子生物学、细胞... 详细信息

急性髓系白血病和骨髓增生异常综合征是常见的髓系恶性肿瘤, 异基因造血干细胞移植是其治愈的主要手段之一, 但对于高危患者, 复发率可超过40%, 移植后复发患者预后极差, 因此移植后预防复发至关重要。移植后血液学、分子生物学、细胞遗传学持续阴性时预防复发的干预措施称为维持治疗。目前常用的维持治疗为应用去甲基化药物、靶向药物等, 但其必要性、给药方案、不良反应、多药联合等方面亟待研究。文章将以药物分类为基础, 系统性阐述高危髓系恶性肿瘤移植后维持治疗的进展。

关键词：白血病髓样急性骨髓增生异常综合征异基因造血干细胞移植维持治疗

造血干细胞移植后难治性/耐药性巨细胞病毒感染诊疗进展

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中华血液学杂志 2024年第11期45卷 1058-1064页

作者：张潇予姜尔烈中国医学科学院血液病医院(中国医学科学院血液学研究所)北京协和医学院血液与健康全国重点实验室国家血液系统疾病临床医学研究中心天津市血液病细胞治疗研究重点实验室细胞生态海河实验室天津300020 天津医学健康研究院天津301600

巨细胞病毒(CMV)感染是造血干细胞移植(HSCT)后最常见的机会性感染之一。尽管预防和抢先治疗可以降低CMV感染和CMV病的发生率,但仍有部分患者发展为难治性/耐药性(R/R)CMV感染,严重影响预后。对抗CMV治疗药物不耐受和发生耐药是患者发... 详细信息

巨细胞病毒(CMV)感染是造血干细胞移植(HSCT)后最常见的机会性感染之一。尽管预防和抢先治疗可以降低CMV感染和CMV病的发生率,但仍有部分患者发展为难治性/耐药性(R/R)CMV感染,严重影响预后。对抗CMV治疗药物不耐受和发生耐药是患者发展为难治的重要原因。在CMV DNA定量PCR的基础上联合使用CMV特异性免疫介导(CMI)监测可以优化R/R CMV感染的诊断并指导个性化治疗。近年来,新型抗病毒药物、免疫治疗包括免疫球蛋白和病毒特异性T细胞治疗的探索,有望为该类患者提供更多的治疗选择。

关键词：巨细胞病毒感染机会性感染个性化治疗 CMV感染 DNA定量病毒特异性免疫介导抗病毒药物

新型靶向药吉瑞替尼在伴FLT3突变急性髓系白血病治疗的临床应用进展

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白血病．淋巴瘤 2023年第6期32卷 377-381页

作者：张荣莉姜尔烈中国医学科学院血液病医院(中国医学科学院血液学研究所)实验血液学国家重点实验室国家血液系统疾病临床医学研究中心、细胞生态海河实验室天津300020

伴有FLT3突变的急性髓系白血病(AML)患者复发风险高、预后差, 以索拉非尼为代表的一代靶向FLT3的药物在治疗AML中存在选择性差、疗效弱等特征, 以吉瑞替尼为代表的新型的二代FLT3抑制剂对FLT3的抑制作用更强、特异性更高、脱靶毒性更低,... 详细信息

伴有FLT3突变的急性髓系白血病(AML)患者复发风险高、预后差, 以索拉非尼为代表的一代靶向FLT3的药物在治疗AML中存在选择性差、疗效弱等特征, 以吉瑞替尼为代表的新型的二代FLT3抑制剂对FLT3的抑制作用更强、特异性更高、脱靶毒性更低, 大大提高了伴FLT3突变的AML患者的疗效。文章就吉瑞替尼的作用机制及临床应用进展进行综述。

关键词：白血病髓系急性基因突变 fms样酪氨酸激酶3 吉瑞替尼

Loss of Lkb1 impairs Treg function and stability to aggravate graft-versus-host disease after bone marrow transplantation

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Cellular & Molecular Immunology 2020年第5期17卷 483-495页

作者： Xiuhua Su Qianqian Wang Wei Guo Xiaolei Pei Qing Niu Maolan Liu Yuanyuan Liu Song Chen Sizhou Feng Yi He Donglin Yang Rongli Zhang Qiaoling Ma Weihua Zhai Aiming Pang Jialin Wei Yong Huang Yuechen Luo Mingzhe Han Xiaoming Feng erlie jiang State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical College300020 TianjinChina Department of Hematology the First Affiliated Hospital of Kunming Medical UniversityHematology Research Center of Yunnan Province650000 KunmingChina

Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely *** this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic *** from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased *** profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD ***3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,***,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease *** findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.

关键词： allogeneic hematopoietic stem cell transplantation(allo-HSCT) acute graft-versus-host disease(aGVHD) Lkb1 Treg

Colony-stimulating factor 3 receptor (CSF3R) M696T mutation does not impact on clinical outcomes of a Ph+ acute lymphoblastic leukemia patient

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Blood Science 2021年第3期3卷 87-92页

作者： Xin Chen Bichen Wang Aiming Pang Weiping Yuan erlie jiang Yajing Chu Sizhou Feng Mingzhe Han State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

Colony-stimulating factor 3 receptor(CSF3R)mutations have been identified in a variety of myeloid *** CSF3R point mutations(eg,T618I)are emerging as key players in chronic neutrophilic leukemia/atypical chronic myelogenous leukemia,the significance of rarer CSF3R mutations is ***,we report a 32-year-old female who was diagnosed as Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph^(+)ALL)with the CSF3R M696T mutation and was undergone unrelated donor hematopoietic stem cell *** patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor(TKI)and long-term survival by unrelated donor ***,we performed a series of experiments using murine interleukin 3(IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T *** confirmed the presence of a CSF3R M696T germline mutation in this patient which was inherited from her *** in vitro experiment results showed that the CSF3R M696T mutation contributes marginally to the tumor transformation of Ba/F3 cells,indicating that CSF3R M696T mutation was neutral in tumor transformation *** concluded that TKI is effective in patients with the CSF3R M696T mutation in Ph+ALL and donors with CSF3R M696T mutation might still be selected as the candidate for transplantation.

关键词： CSF3R M696T mutation Familial inheritance Pathogenicity Ph+acute lymphoblastic leukemia

靶向治疗及免疫治疗时代造血干细胞移植在急性白血病中的应用

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临床血液学杂志 2023年第9期36卷 615-621页

作者：姜尔烈郑亚伟中国医学科学院血液病医院(中国医学科学院血液学研究所) 天津300020

目前造血干细胞移植已成为急性白血病治疗中不可或缺的组成部分。虽然过去20年来靶向治疗及免疫治疗迅速发展,提高了急性白血病的疗效,但造血干细胞移植的治疗地位依然不可取代。本文介绍了当前造血干细胞移植在急性白血病治疗中的作用... 详细信息

目前造血干细胞移植已成为急性白血病治疗中不可或缺的组成部分。虽然过去20年来靶向治疗及免疫治疗迅速发展,提高了急性白血病的疗效,但造血干细胞移植的治疗地位依然不可取代。本文介绍了当前造血干细胞移植在急性白血病治疗中的作用,及靶向治疗与免疫治疗与造血干细胞移植结合对急性白血病患者疗效的改善。

关键词：自体造血干细胞移植异基因造血干细胞移植靶向治疗免疫治疗

Single-cell transcriptomic landscape of human blood cells

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National Science Review 2021年第3期8卷 42-52页

作者： Xiaowei Xie Mengyao Liu Yawen Zhang Bingrui Wang Caiying Zhu Chenchen Wang Qing Li Yingying Huo Jiaojiao Guo Changlu Xu Linping Hu Aiming Pang Shihui Ma Lina Wang Wenbin Cao Shulian Chen Qiuling Li Sudong Zhang Xueying Zhao Wen Zhou Hongbo Luo Guoguang Zheng erlie jiang Sizhou Feng Lixiang Chen Lihong Shi Hui Cheng Sha Hao Ping Zhu Tao Cheng State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences &Peking Union Medical College Center for Stem Cell Medicine and Department of Stem Cell & Regenerative Medicine Chinese Academy of Medical Sciences and Peking Union Medical College Cancer Research Institute School of Basic Medical Science Central South University School of Life Sciences Zhengzhou University

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying ***,an elaborate and comprehensive transcriptome reference of the whole blood system is ***,we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types,including hematopoietic stem cells,progenitors and mature blood cells derived from 21 healthy *** high sequencing depth and coverage,we constructed a single-cell transcriptional atlas of blood cells(ABC) on the basis of both protein-coding genes and long noncoding RNAs(lncRNAs),and showed a high consistence between ***,putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were *** common transcription factor regulatory networks were activated in neutrophils and monocytes,lymphoid cells dramatically changed their regulatory networks during ***,we showed a subset of nucleated erythrocytes actively expressing immune signals,suggesting the existence of erythroid precursors with immune ***,a web portal offering transcriptome browsing and blood cell type prediction has been ***,our work provides a transcriptional map of human blood cells at single-cell resolution,thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

关键词： human hematopoietic cells lncRNAs transcription factor single-cell RNA-seq