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Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation

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Chinese Medical Journal 2013年第13期126卷 2489-2494页

作者： mo xiao-dong xu lan-ping liu dai-hong zhang xiao-hui chen huan chen yu-hong han wei wang yu wang feng-rong wang jing-zhi liu kai-yan huang xiao-jun Peking University People's Hospital & Institute of Hematology Beijing Key laboratory of Hematopoitic Stem Cell Transplantation Beijing 100044 China

Background The occurrence of bronchiolitis obliterans syndrome （BOS） after allogeneic hematopoietic stem cell transplantation （alIo-HSCT） is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after alIo-HSCT. Methods A nested case-control study was designed. Cases with BOS and controls matched for the year of alIo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent alIo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia. Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was （32.7±2.4） years, and the mean time to presentation was （474±350） days post-HSCT. A pre-HSCT cyclophosphamide dose of 〉3.2 g/m2 （OR=8.74, P=0.025）, chronic graft-versus-host disease （moderate to severe）（OR=12.02, P=0.000）, and conditioning regimens without antithymocyte globulin （OR=2.79, P=0.031） were independently associated with BOS. Conclusions We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after alIo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.

关键词： bronchiolitis obliterans syndrome allogeneic hematopoietic stem cell transplantation graft-versus-host disease,"antithymoeyte globulin

Disease Risk Comorbidity Index for Patients Receiving Haploidentical Allogeneic Hematopoietic Transplantation

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Engineering 2021年第2期7卷 162-169页

作者： xiao-dong mo xiao-hui zhang lan-ping xu yu wang chen-Hua yan huan chen yu-hong chen wei han feng-rong wang jing-zhi wang kai-yan liu xiao-jun huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing100044China Peking–Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences(2019RU029)Beijing 100073China

We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before *** this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia *** score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.

关键词： Disease risk index Disease risk comorbidity index Hematopoietic cell transplantation comorbidity index Hematopoietic stem cell transplantation Haploidentical

CEPC Technical Design Report

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Radiation Detection Technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai yu Bai yang Bai Vipul Bairathi Csaba Balazs Philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci xiao-jun Bi yuanjie Bi Tianjian Bian Fabrizio Bianchi Thomas Biekotter Michela Biglietti Shalva Bilanishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert Maarten Boonekamp Marcello Borri Angelo Bosotti Vincent Boudry mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya Masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia Hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai yuchen Cai Haiying Cai Huacheng Cai Lorenzo Calibbi junsong Cang Guofu Cao Jianshe Cao Antoine Chance xuejun Chang yue Chang Zhe Chang Xinyuan Chang wei Chao Auttakit Chatrabhuti Yimin Che yuzhi Che Bin chen Danping chen Fuqing chen Fusan chen Gang chen Guoming chen Hua-Xing chen huirun chen Jinhui chen Ji-yuan chen kai chen Mali chen Mingjun chen Mingshui chen Ning chen Shanhong chen Shanzhen chen Shao-Long chen Shaomin chen Shiqiang chen Tianlu chen wei chen Xiang chen xiaoyu chen Xin chen xun chen xurong chen Ye chen Ying chen yukai chen Zelin chen Zilin chen Gang chen Boping chen Chunhui chen Hok Chuen cheng Huajie cheng Shan cheng Tongguang cheng yunlong Chi Pietro Chimenti Wen han Chiu Guk Cho Ming-Chung Chu xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin hanhua Cui xiaohao Cui Zhaoyuan Cui Brunella D'Anzi Ling-yun dai Xinchen dai xuwen dai Antonio De Maria Nicola De Filippis Christophe De La Taille Francesca De mori Chiara De Sio Elisa Del Core Shuangxue Deng wei-Tian Deng zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding Haiyi dong Jianin AGH University of Science and Technology Faculty of Physics and Applied Computer ScienceKrakow Anhui University HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu University Institute of ScienceVaranasi Bandirma Onyedi Eylul University Bandirma Beihang University Beijing Beijing Computational Science Research Center Beijing Beijing Conveyi LTD Beijing Beijing Glass Research Institute Co. LtdBeijing Beijing Institute of Technology Beijing Beijing Normal University Beijing Brown University ProvidenceRI Budker Institute of Nuclear Physics Novosibirsk Cadi Ayyad University Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo University Giza Center for Theory and Computation National Tsing Hua UniversityHsinchu Central China Normal University WuhanHubei Central South University ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa chengdu kaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan China academy of engineering physics MianyangSichuan China building materials academy Beijing China Center of Advanced Science and Technology Beijing China Institute of Atomic Energy Beijing China Jiliang University HangzhouZhejiang China Nuclear Instrument CO. LTDBeijing China University of Geosciences Beijing China University of Geosciences WuhanHubei China University of Mining and Technology XuzhouJiangsu China West Normal University NanchongSichuan Chongqing University Department of PhysicsChongqing Chulalongkorn University Bangkok City University of hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell University IthacaNY CPPM(AMU/IPhU&CNRS/INP) Marseille Dalian Minzu University DalianLiaoning Dalian University of Technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov Laboratory of Nuclear Problems of Joint Institute for Nuclear Research(DLNP JINR) Dubna East China University Of Science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2030s.

关键词： initiated exceeding precise

Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies： a single-institute analysis

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Chinese Medical Journal 2013年第13期126卷 2499-2503页

作者： chen yu-hong xu lan-ping liu dai-hong chen huan zhang xiao-hui han wei wang feng-rong wang Jin-zhi wang yu huang xiao-jun liu kai-yan Peking UniversityPeople's Hospital Peking University Institute of Hematology Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044 China China Peking-Tsinghua Center for Life Sciences Beijing 100044 China

Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival （LFS） and some primary results, such as hematologic recovery, risk of graft-versus-host disease （GVHD）, relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source. Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood （UCBT） as a primary unrelated stem cell source （n=38）, bone marrow （UBMT n=28, transplanted before January 2003）, or peripheral blood stem cells （UPBSCT n=46, transplanted after January 2003） between July 2000 and July 2008 were analyzed. Results Except that the patients were much younger in the UCBT group （median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT）, other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti- thymocyte globulin （ATG） used for the UBMT patients （2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000）. Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower （87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000） for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease （aGVHD） was much higher in the UBMT group but did not differ among the other groups （51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000）. The occurrence of extensive chronic GVHD （cGVHD） was significantly decreased for recipients of UCBT （4%） compared with that of UPBSCT （39.1%） and UBMT （49

关键词： cord blood transplantation unrelated donor hematopoietic stem cell transplantation

modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

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Chinese Medical Journal 2007年第6期120卷 463-468页

作者： zhang xiao-hui huang xiao-jun liu kai-yan xu lan-ping liu dai-hong chen huan chen yu-hong wang jing-zhi han wei LU Dao-pei Institute of Hematology Peking University People＇s Hospital Beijing 100044 China

Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma. Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea （40 mg/kg） was administered twice on day -10 and cytarabine （2 g/ms） was given on day -9, busulfan was administered orally in four divided doses daily for 3 days （days -8 to -6）. The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days -5 and -4 （1.8 g/m^2）, and with semustine （Me-CCNU） 250 mg/m^2 on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease （GVHD, 36.4%; 95% CI： 13.9%-38.6%）. Two patients （18.2%） developed grade Ⅰ acute GVHD （95% CI： 10.9%-35.9%） and grade Ⅱ acute GVHD occurred in one patient （9.1%; 95% Cl. 8.4%-32.3%）. Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% （95% Cl： 11.7%-36.7%）, among them one died of severe grade IV GVHD and one developed multiorgan failure on day ＋170; the treatment-related mortality was 22.0% （95% Cl： 10.3%-34.1%）. The overall 4-year survival rate was 67.8% （95% Cl： 16.3%-46.7%）. The estimated 4-year progr

关键词： multiple myeloma stem cell transplantation modified conditioning regimen

Allo-hematopoietic stem cell transplantation is a potential treatment for a patient with a combined disorder of hereditary spherocytosis

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Chinese Medical Journal 2012年第5期125卷 947-950页

作者： zhang xiao-hui FU Hai-xia xu lan-ping liu dai-hong chen huan han wei chen yu-hong wang feng-rong wang jing-zhi wang-yu ZHAO Ting liu kai-yan huang xiao-jun Peking University People's Hospital Peking University Institute of HematologyBeijing 100044China

Both human hereditary spherocytosis （HS） and chronic myelogenous leukemia （CML） are life threatening. Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation. The complete donor erythroid cells were obtained. The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation （HSCT）. Reticulocyte counts normalized, and BCR-ABL was cleared away. The total bilirubin level was also corrected in this recipient. Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation. HS was not a contraindication for patient in the matched sibling transplant setting.

关键词： hereditary spherocytosis allogeneic stem cell transplantation, chronic myelogenous leukemia

Idiopathic inflammatory demyelinating diseases of the central nervous system in patients following allogeneic hematopoietic stem cell transplantation： a retrospective analysis of incidence, risk factors and survival

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Chinese Medical Journal 2013年第6期126卷 1096-1102页

作者： zhang xiao-hui huang xiao-jun liu kai-yan xu lan-ping liu dai-hong chen huan han wei chen yu-hong wang feng-rong wang jing-zhi wang yu ZHAO Ting chen Yao FU Hai-xia wang Min Peking University People's Hospital Peking University Institute of Hematology Beijing 100044 China

Background AIIogeneic hematopoietic stem cell transplantation （allo-HSCT） is a curative therapy for many hematological diseases, but there are many complications following alIo-HSCT, among which neurological complications （NC） are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases （IIDDs） of the central nervous system （CNS） in patients following alIo-HSCT. Methods A nested case-control study was conducted in a large cohort of 1365 patients, who underwent alIo-HSCT at the Institute of Hematology and Peking University People＇s Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0. Results The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients （97.2%） suffered IIDDs after transplantation, 16 patients （44.4%） between day 0 to day 100 post-transplantation, 10 patients （27.8%） between day 100 to 1 year post-transplantation, and 9 patients （25.0%） 1 year post-transplantation. Multivariate regression analysis identified donor type （P=0.031）, infection （P=0.009）, and acute lymphatic leukemia （P=0.017） as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation （95% CI： 223-805）. Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not （26.6% vs. 73.5%, P 〈0.001）. Of the 36 patients experiencing IIDDs, 58.3% （n=21） died. The causes of death were graft-versus-host disease （GVHD）（n=4）, underlying disease relapse （n=3）, infections （n=12）, and other causes （n=2）. Conclusions IIDDs is an uncommon but serious complication of alIo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, and infections. Our study results in

关键词： hematopoietic stem cell transplantation idiopathic inflammatory demyelinating diseases central nervous system risk factors survival

The role of collateral related donors in haploidentical hematopoietic stem cell transplantation

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Science Bulletin 2018年第20期63卷 1376-1382页

作者： xiao-dong mo yuan-yuan zhang xiao-hui zhang lan-ping xu yu wang chen-Hua yan huan chen yu-hong chen Ying-jun Chang kai-yan liu xiao-jun huang Peking University People's Hospital Peking University Institute of hematologyBeijing 100044China Peking-Tsinghua Center for Life Sciences Beijing 100871China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China

A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, *** donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.

关键词： Haploidentical Hematopoietic stem cell transplantation Collateral related donors Paternal donors Maternal donors

Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation

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Cellular & molecular Immunology 2021年第5期18卷 1172-1185页

作者： huidong Guo Ying-jun Chang yan hong lan-ping xu yu wang xiao-hui zhang Ming wang huan chen yu-hong chen feng-rong wang wei-han yu-Qian Sun chen-Hua yan Fei-Fei Tang xiao-dong mo kai-yan liu xiao-jun huang Peking University People’s Hospital&Peking University Institute of Hematology National Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationNo.11 South Street of XizhimenXicheng District100044BeijingChina Peking-Tsinghua Center for Life Sciences 100871BeijingChina Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences2019RU029BeijingChina

Haploidentical stem cell transplantation(haplo-SCT)achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation(MSDT)in treating hematological *** define the underlying regulatory dynamics,we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple ***,we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility(MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in *** found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia *** stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor–α,interferon-γ,pore-forming proteins and CD107a secreted by T cells or natural killer ***,we conducted a prospective clinical trial which enrolled 135 patients with t(8;21)acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or *** results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with *** vivo experiments showed that,1 year after transplantation,cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same *** results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.

关键词： Graft-versus-leukemia Haplo-SCT MSDT AML MRD