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Risk factors associated with hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Blood Science 2022年第2期4卷 83-88页

作者： Biao Shen Yueshen Ma Haixiao Zhang Mingyang Wang Jia Liu Jiaxin Cao Wenwen Guo Dan Feng Donglin Yang Rongli Zhang Xin Chen Qiaoling Ma Weihua Zhai Sizhou Feng Mingzhe Han Aiming Pang erlie jiang 无 State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHematopoietic Stem Cell Transplantation CenterInstitute of Hematology and Blood Diseases HospitalPeking Union Medical College and Chinese AcademyTianjinChina Administration Office of Biostatistics Center for Information and ResourcesInstitute of Hematology and Blood Diseases HospitalPeking Union Medical College and Chinese AcademyTianjinChina Office of Institute of Hematology and Blood Diseases Hospital Peking Union Medical College and Chinese AcademyTianjinChina

Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painful urination,which brings great pain.This study aimed to analyze risk factors of HC and its effect on patient survival.We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020.Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex,age,and diagnosis,and logistic regression analyses were used to identify factors associated with HC.We used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC groups.We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve(ROC)analysis.After propensity score matching,there were 131 patients each in the HC and non-HC groups.In the HC group,89 patients(67.9%)had mild HC(stage II°)and 43(32.1%)had severe HC(stage III–IV).The median interval between stem cell transplantation and HC development was 31(3–244)days.Univariate analysis indicated that donor age,hematopoietic stem cell source,HLA,acute graft-versus-host disease,busulfan,anti-thymocyte globulin(ATG),total body irradiation,cytomegalovirus(CMV)(urine),and BK polyomavirus(BKV)(urine)were significantly associated with HC.ATG,CMV(urine),and BKV(urine)were independent risk factors for HC based on the multivariate analysis.The Kaplan–Meier survival analysis showed no significant difference between the HC and non-HC groups(P=0.14).The 1-and 2-year survival rates in the HC group were 78.4%and 69.6%,respectively,and the corresponding rates in the non-HC group were 84.4%and 80.7%,respectively.ROC analysis indicated that a urine BKV load of 1×10^(7) copies/mL was able to stratify the risk of HC.In conclusion,when the BKV load is>1×10^(7),we needtobe aware of the potential for the development of HC.

关键词： Allogeneic hematopoietic stem cell transplantation Hemorrhagic cystitis Prognosis Risk factors

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Intravenous-oral itraconazole versus oral posaconazole in preventing invasive fungal diseases for acute leukemia patients

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Blood Science 2023年第2期5卷 106-110页

作者： Li Liua Xiaolei Peia Runzhi Maa Yi Hea Rongli Zhanga Jialin Weia Qiaoling Maa Weihua Zhaia Aiming Pang erlie jiang Mingzhe Han Donglin Yang Sizhou Feng Hematopoietic Stem Cell Transplantation Center National Clinical Research Center for Blood DiseasesState Key Laboratory of Experimental HematologyHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×2 days followed by 5 mg/kg·d orally in twice)or oral suspension of posaconazole(200 mg Q8h)was administered for preventing IFDs.The only 2 episodes of proven IFDs were not included after propensity-score matching(PSM),while the incidence of possible IFDs was 8.2%(9/110)in itraconazole group and 1.8%(2/110)in posaconazole group,respectively(P=.030).In clinical failure analysis,the failure rate of posaconazole group was lower as compared to the itraconazole group(2.7%vs 10.9%,P=.016).Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs,while posaconazole suspension seems more tolerable.

关键词： Acute leukemia Antifungal prophylaxis Invasive fungal disease Itraconazole Posaconazole

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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 disorders.Although 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 unknown.Here,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 transplantation.The patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor(TKI)and long-term survival by unrelated donor transplantation.Meanwhile,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 mutation.We confirmed the presence of a CSF3R M696T germline mutation in this patient which was inherited from her mother.The 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 ability.We 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

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Risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia

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Blood Science 2022年第3期4卷 164-169页

作者： Juan Chen Aiming Pang Yuanqi Zhao Li Liu Runzhi Ma Jialin Wei Xin Chen Yi He Donglin Yang Rongli Zhang Weihua Zhai Qiaoling Ma erlie jiang Mingzhe Han Jiaxi Zhou Sizhou Feng State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

Objective:To investigate the risk factors for cytomegalovirus(CMV)infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed.Results:Of 359 patients,48.19%(173)patients experienced CMV infection within 100 days posttransplantation.In univariate and multivariate logistic analysis,haploidentical-related donor(HRD)(P<0.001;odds ratio[OR],5.542;95%confidence interval[CI],3.186–9.639),and ratio of CD3^(+)CD8^(+)cells in lymphocytes<14.825%(P<0.001;OR,3.005;95%CI,1.712–5.275)were identified as 2 independent risk factors.One-year relapse rate(RR)between the CMV infection group and the non-CMV infection group was not statistically significant(18.5%vs 19.9%,P=0.688).When we divided the total cohort into AML,ALL,and MAL subgroups,there were no significant differences as well(P=0.138;P=0.588;P=0.117;respectively).Conclusion:In conclusion,donor type(HRD)and the insufficient recovery of CD3^(+)CD8^(+)cells were independent risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia.CMV infection within 100 days did not influence the incidence of relapse in 1 year for patients with acute leukemia.

关键词： Acute leukemia Allogeneic hematopoietic stem cell transplantation Cytomegalovirus Risk factors Relapse

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生物制剂治疗胃肠道急性移植物抗宿主病的研究进展

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中华内科杂志 2024年第1期63卷 107-112页

作者：吴静怡刘响王斯南姜尔烈王邦茂曹海龙天津医科大学总医院消化科天津市消化疾病研究所天津300052 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

异基因造血干细胞移植(allo-HSCT)是多种血液系统疾病的有效治疗手段,但移植物抗宿主病(GVHD)仍是移植后并发症和非复发性死亡的主要原因,其中胃肠道急性GVHD预示着患者的不良结局。急性GVHD患者一线治疗推荐使用全身性糖皮质激素,但仍... 详细信息

异基因造血干细胞移植(allo-HSCT)是多种血液系统疾病的有效治疗手段,但移植物抗宿主病(GVHD)仍是移植后并发症和非复发性死亡的主要原因,其中胃肠道急性GVHD预示着患者的不良结局。急性GVHD患者一线治疗推荐使用全身性糖皮质激素,但仍有大部分患者对激素无应答。鉴于生物制剂在炎症性肠病等疾病中的显著疗效,其作为难治性急性GVHD的二线治疗也备受关注。本文就生物制剂在胃肠道急性GVHD的疗效及安全性等方面进行阐述,旨在为合理应用提供参考。

关键词：造血干细胞移植移植物抗宿主病胃肠道生物制剂治疗效果

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异基因造血干细胞移植治疗≤50岁高危多发性骨髓瘤患者14例临床分析

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中华血液学杂志 2024年第1期45卷 28-34页

作者：潘攀王佳丽翟卫华马巧玲杨栋林冯四洲韩明哲庞爱明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) 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细胞生态海河实验室天津300020 天津医学健康研究院天津301600

目的观察异基因造血干细胞移植(allo-HSCT)对年轻(≤50岁)高危多发性骨髓瘤(HRMM)患者的疗效。方法纳入2016年11月至2022年11月期间于中国医学科学院血液病医院造血干细胞移植中心接受allo-HSCT的14例具有高危细胞遗传学改变或高危疾病... 详细信息

目的观察异基因造血干细胞移植(allo-HSCT)对年轻(≤50岁)高危多发性骨髓瘤(HRMM)患者的疗效。方法纳入2016年11月至2022年11月期间于中国医学科学院血液病医院造血干细胞移植中心接受allo-HSCT的14例具有高危细胞遗传学改变或高危疾病生物学因素的年轻(≤50岁)HRMM患者,对其临床资料进行回顾性分析。结果14例患者中,男7例,女7例,移植时中位年龄为39.5(31~50)岁。患者移植前中位治疗线数为2(1~6)线,移植前6例患者未达完全缓解(CR),5例患者微小残留病(MRD)阳性。14例患者均获得造血重建,中性粒细胞、血小板中位植入时间分别为11(10~14)d、13(9~103)d。5例患者发生Ⅱ~Ⅳ度急性移植物抗宿主病(GVHD),2例患者发生中重度慢性GVHD。移植后3个月疗效评估,所有患者均为严格意义的完全缓解(sCR)。移植后中位随访时间为18.9(4.1~72.5)个月,移植后2年移植相关死亡率为7.1%(95%CI 0%~21.1%),总生存率为92.9%(95%CI 80.3%~100.0%);移植后1、2年无进展生存率分别为92.9%(95%CI 80.3%~100.0%)、66.0%(95%CI 39.4%~100.0%),2年累积复发率为28.9%(95%CI 0%~56.7%)。结论年轻HRMM患者在诱导治疗后桥接allo-HSCT可进一步提高疗效。

关键词：异基因造血干细胞移植多发性骨髓瘤高危

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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 unknown.In 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 reconstitution.Tregs 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 apoptosis.Transcriptional 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 patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These 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

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异基因造血干细胞移植治疗DEK-NUP214融合基因阳性急性髓系白血病患者12例疗效分析

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中华血液学杂志 2024年第4期45卷 383-387页

作者：申昱妍杨栋林何祎庞爱明陈欣马巧玲张荣莉魏嘉璘翟卫华韩明哲姜尔烈冯四洲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) 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细胞生态海河实验室天津300020 天津医学健康研究院天津301600

2016年11月至2022年8月期间,12例DEK-NUP214融合基因阳性急性髓系白血病患者在中国医学科学院血液病医院接受异基因造血干细胞移植(allo-HSCT)。12例患者中男5例,女7例,中位年龄34(16~52)岁。12例患者初诊时均检出DEK-NUP214融合基因阳... 详细信息

2016年11月至2022年8月期间,12例DEK-NUP214融合基因阳性急性髓系白血病患者在中国医学科学院血液病医院接受异基因造血干细胞移植(allo-HSCT)。12例患者中男5例,女7例,中位年龄34(16~52)岁。12例患者初诊时均检出DEK-NUP214融合基因阳性,10例患者染色体核型分析显示t(6;9)(p23;q34)易位(2例患者未行染色体核型分析),11例患者检出FLT3-ITD突变,11例患者检出WT1高表达。9例患者allo-HSCT前处于第一次完全缓解状态,1例患者疾病未缓解,2例患者处于复发状态。所有患者均接受清髓性预处理,5例患者接受同胞全相合造血干细胞移植,7例患者接受单倍体造血干细胞移植。移植物单个核细胞中位数为10.87(7.09~17.89)×10^(8)/kg,CD34^(+)细胞中位数为3.29(2.53~6.10)×10^(6)/kg。所有患者均获得造血重建,粒细胞植入中位时间为14(10~20)d,血小板植入中位时间为15(9~27)d。移植后1年移植相关死亡率为21.2%。移植后1、3年累积复发率分别为25.0%、50.0%,无白血病生存率为(65.6±14.0)%,总生存率为(72.2±13.8)%。

关键词：急性髓系白血病中国医学科学院造血干细胞移植造血重建移植物染色体核型分析总生存率 DEK

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Decitabine in combination with idarubicin within a modified busulfan/cyclophosphamide conditioning regimen for patients with advanced myelodysplastic syndrome: A prospective multicenter clinical cohort study

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中华医学杂志(英文版) 2024年第9期137卷 2024 Feb 2页

作者： Cao Yigeng Wang Mingyang Wang Fuxu Guo Wenwen Ma Yueshen Li Xiaoyun He Yi Pang Aiming Zhang Rongli Zhai Weihua Chen Xin Ma Qiaoling Wei Jialin Yang Donglin Huang Yong Feng Dan Liu Jia Gao Xin Wen Shupeng Wang Wen Wang Tao Li Ying Fang Xiaosheng Li Yingchun Zhang Xiaohan Cai Yun Wang Yongqi Cao Weijie Lu Runqing Feng Sizhou Guo Rong Fu Yuewen Du Xin Liu Zhuogang Wang Xin Wang Ling Ma Liangming Liu Chuanfang Zhang Xuejun Han Mingzhe jiang erlie China Department of Hematology Second Hospital of Hebei Medical University Hebei Key Laboratory of Hematology Shijiazhuang Hebei China Center for Information and Resource State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Department of Hematopoietic Stem Cell Transplantation Center Haihe Laboratory of Cell Ecosystem Institute of Hematology Blood Diseases Hospital Chinese Academy of Medical Sciences & Department of Hematology Qilu Hospital of Shandong University Jinan Shandong China Department of Hematology State Key Laboratory of Experimental Hematology Shanxi Bethune Hospital Third Hospital of Shanxi Medical University Taiyuan Shanxi China Department of Hematology Qingdao Central Hospital University of Health and Rehabilitation Sciences Qingdao Shandong National Clinical Research Center for Blood Diseases China Department of Hematology Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan Shandong China Department of Hematology Shandong Provincial Hospital Affiliated to Shandong First Medical University Haihe Laboratory of Cell Ecosystem Jinan Shandong China Department of Hematology Shengjing Hospital of China Medical University Shenyang Liaoning China Department of Hematology Shenzhen Second People’s Hospital Institute of Hematology The First Affiliated Hospital of Shenzhen University Shenzhen University School of Medicine Shenzhen Guangdong China Department of Hematology Henan Cancer Hospital Cancer Hospital Affiliated Zhengzhou University Zhengzhou Henan Blood Diseases Hospital China Department of Hematology Department of Hematology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin

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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 hematopoiesis.However,an elaborate and comprehensive transcriptome reference of the whole blood system is lacking.Here,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 donors.With 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 them.Notably,putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified.While common transcription factor regulatory networks were activated in neutrophils and monocytes,lymphoid cells dramatically changed their regulatory networks during differentiation.Furthermore,we showed a subset of nucleated erythrocytes actively expressing immune signals,suggesting the existence of erythroid precursors with immune functions.Finally,a web portal offering transcriptome browsing and blood cell type prediction has been established.Thus,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

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