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Haploidentical hematopoietic cell transplantation for severe acquired aplastic anemia: a case-control study of post-transplant cyclophosphamide included regimen vs. anti-thymocyte globulin & colony-stimulating factor-based regimen

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Science China(Life Sciences) 2020年第6期63卷 940-942页

作者： Lanping Xu Bin Fu Wenjing Wang Yajing Xu Depei Wu Shunqing Wang Qifa Liu Linghui Xia Sujun Gao Ming Jiang Jianmin Wang Xi Zhang Hai Bai Huiren Chen Chunfu Li Xiaojun Huang Institute of hematology Peking UniversityPeking University People’s HospitalBejing 100044China Department of hematology Xiangya HospitalCentral South UniversityChangsha 410008China Department of hematology the First Affiliated Hospital of Soochow UniversitySoochow 215000China Department of hematology Guangzhou First People’s HospitalGuangzhou 510180China Department of hematology Nanfang Hospital affiliated to Southern Medical UniversityGuangzhou 510515China Department of hematology Xiehe Hospital affiliated to Huazhong University of Science and TechnologyWuhan 430022.China Department of hematology the First Hospital of Jilin UniversityChangchun 130021China Department of hematology the First Affiliated Hospital of XinjiangMedical UniversityUrumchi 830054China Department of hematology Changhai Hospital affiliated to Second Military Medical UniversityShanghai 200000 China Department of hematology Xinqiao Hospital affiliated to Third Military Medical UniversityChongqing 400037China Department of hematology Lanzhou Military Area General HospitalLanzhou 730050China Department of hematology The Military General Hospital of Beijing PLABeijing 100700China Department of Pediatrics Nanfang Hospital affiliated to Southern Medical UniversityGuangzhouu 510515China Beijing Key Laboratory of Hematopoietic Stem cell Transplantation Bejing 100444China

Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for *** models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with *** first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).

关键词： CSF anti-thymocyte globulin colony-stimulating factor-based regimen Haploidentical hematopoietic cell transplantation for severe acquired aplastic anemia a case-control study of post-transplant cyclophosphamide included regimen vs

Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

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Chinese Medical Journal 2014年第20期127卷 3602-3609页

作者： Yan Chenhua Xu Lanping Liu Daihong Chen Huan Wang Yu Liu Kaiyan Huang Xiaojun Department of hematology Peking University People's HospitalPeking University Institute of Hematology Beijing Key Laboratoryof Hematopoietic Stem Cell Transplantation Beijing 100044 China

Background In haploidentical hematopoietic stem cell transplantation （HSCT）, the duration of graft-versus-host disease （GVHD） prophylaxis after modified donor lymphocyte infusion （DLI） was the only risk factor of DLI-associated grades 3-4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia （GVL） effect. Therefore, this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for 〈6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease （MRD）-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for 〈6 weeks. Results First, compared with prophylaxis for 〈6 weeks, prophylaxis for 6-8 weeks reduced incidence of relapse in total patients （26.6% vs. 69.0%, P 〈0.001）. Besides, prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant （P=0.018） and in 49 patients developing MRD-positive status post-transplant （P 〈0.001）. Second, prophylaxis for 6-8 weeks reduced incidence of acute GVHD （P 〈0.05）, reduced the therapeutic application of immunosuppressive agents （P=0.019）, but increased the incidence of chronic GVHD （P〈0.05）. Third, prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant （P 〈0.05）. Conclusions In haploidentical HSCT, prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for 〈6 weeks. This strategy wil

关键词： allogeneic hematopoietic stem cell transplantation haploidentical graft-versus-host disease modified donor lymphocyte infusion graft-versus-leukemia effects

Immunotherapy for multiple myeloma: new chances and hope

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Cancer Biology & Medicine 2023年第10期20卷 695-700页

作者： Jingyu Xu Gang An Lugui Qiu State Key Laboratory of Experimental hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Science&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China

Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic *** of its incurable nature,treatments for MM are aimed primarily at obtaining minimal residual disease(MRD)negativity and achieving persistent control,both of which are believed to be important strategies to prolong survival and improve prognosis in patients with MM.

关键词： myeloma prognosis monoclonal

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

Influence of the degree of donor bone marrow hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation

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Science China(Life Sciences) 2020年第1期63卷 138-147页

作者： Feifei Tang Xiaodong Mo Xiaohui Zhang Yu Wang Chenhua Yan Yuhong Chen Huan Chen Wei Han Yao Chen Fengrong Wang Jingzhi Wang Yuqian Sun Yuanyuan Zhang Kaiyan Liu Xiaojun Huang Lanping Xu Peking University People's Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China

This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT from hypoplastic BM donors between January 2010 and December ***-eight patients whose donors demonstrated BM hyperplasia were selected using a propensity score matching method(1:4).Primary graft failure including poor graft function and graft rejection did not occur in two *** BM hypoplasia and hyperplasia groups,the cumulative incidence(CI)of neutrophil engraftment at day 28(91.7%vs.93.8%,P=0.75),platelet engraftment at day 150(83.3%vs.93.8%,P=0.48),the median time to myeloid engraftment(14 days vs.14 days,P=0.85)and platelet engraftment(14 days vs.14 days,P=0.85)were *** 3-year progression-free survival,overall survival,CI of non-relapse mortality and relapse were 67.8%vs.71.7%(P=0.98),69.8%vs.77.8%(P=0.69),18.5%vs.13.6%(P=0.66),and 10.2%vs.10.4%(P=0.82),*** multivariate analysis,donor BM hypoplasia did not affect patient clinical outcomes after *** patients have no other suitable donor,a donor with BM hypoplasia can be used for patients receiving allo-HSCT if the donor Complete Blood Count and other examinations are normal.

关键词： bone marrow aspirate hypoplasia hyperplasic normal donor allogeneic hematopoietic stem cell transplantation

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

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Signal Transduction and Targeted therapy 2021年第11期6卷 3230-3245页

作者： Xia Li Mi Shao Xiangjun Zeng Pengxu Qian He Huang Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou311121People’s Republic of China Institute of hematology Zhejiang UniversityHangzhouZhejiangPeople’s Republic of China Zhejiang Province Engineering Laboratory for Stem cell and Immunity therapy HangzhouZhejiangPeople’s Republic of China Center of Stem cell and Regenerative Medicine Zhejiang University School of MedicineHangzhouPeople’s Republic of China

Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune ***,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ ***,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the *** a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain *** the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of *** that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

关键词： cytokine release kinetics

Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase

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Frontiers of Medicine 2015年第3期9卷 304-311页

作者： Lanping Xua Huanling Zhu Jianda Hu Depei Wu Hao Jiang Qian Jiang Xiaojun Huang Peking University People's Hospital Peking University Institute of Hematology Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044 China West China Hospital Siehuan University Chengdu 610041 China Fujian Medical University Union Hospital Fujian Institute of Hematology Fuzhou 350001 China The First Affiliated Hospital Sooehow University Suzhou 215006 China

In the tyrosine kinase inhibitor （TKI） era, imatinib is the first-line therapy for patients with chronic myeloid leukemia （CML） in chronic or accelerated phase. Although second-generation TKIs （TKI2）, including dasatinib and nilotinib, are appropriate treatment regimens for patients with disease that progressed to accelerated phase following imatinib therapy, allogeneic hematopoietic stem cell transplantation （allo-HSCT） is the only curative therapy. This study retrospectively analyzed the efficacy of TKI2 and HSCT for treatment of CML in accelerated phase. Ninety-three patients with CML registered in the Chinese CML alliance database from February 2001 to February 2014 were enrolled and divided into the TKI2 （n = 33） and allo-HSCT （n = 60） groups. In the TKI2 group, 26 and 7 patients received nilotinib and dasatinib, respectively, as initial TKI2 and 11 patients transferred to the alternative TKI2 after failure to one TKI2. In the allo-HSCT group, 22 （36.7%）, 35 （58.3%）, and 3 （10%） patients underwent aHo-HSCT from an HLA-matched sibling donor, HLA mismatched/haploidentical donor, and unrelated donor, respectively. All patients in the HSCT group were engrafted. Overall, 69.7%, 48.5%, and 45.5% of patients presented hematological, cytogenetic, and major molecular responses, respectively, to at least one of TKI2. All 60 patients （100%） achieved CHR and cytogenetic response in the HSCT group. Patients in the TKI2 group exhibited lower 5-year overall survival rate （42.9% vs. 86.4%, P = 0.002）, 5-year event-free survival rate （14.3% vs. 76.1%, P 〈 0.001）, and 5-year progression-free survival （28.6% vs. 78.1%, P 〈 0.001） than those in the alIo-HSCT group. Multivariate analysis showed that male sex and TKI2 therapy were predictors of poor overall survival, whereas hemoglobin 〈 100 g/L and TKI2 therapy were predictors of poor event-free survival and progression-free survival. These results indicated that allo-HSCT may be superior to nilotinib and dasatinib for adult patien

关键词： chronic myeloid leukemia imatinib dasatinib nilotinib allogeneic hematopoietic stem cell transplantation

Weekly docetaxel and gemcitabine in previously treated metastatic esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2015年第14期21卷 4268-4274页

作者： Min-Young Lee Ki Sun Jung Hae Su Kim Ji Yun Lee Sung Hee Lim Moonjin Kim Hyun Ae Jung Sung Min Kim Jong Mu Sun Myung-Ju Ahn Jeeyun Lee Se Hoon Park Seong Yoon Yi In Gyu Hwang Sang-Cheol Lee Hee Kyung Ahn Do Hyoung Lim Soon Il Lee Keon Woo Park Division of hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of Medicine Division of hematology-Oncology Department of Internal MedicineInje University Ilsan-Paik Hospital Division of hematology-Oncology Department of Internal MedicineChung-Ang University Hospital Division of hematology-Oncology Department of Internal MedicineSoonchunhyang University Hospital Division of hematology-Oncology Department of Internal MedicineGachon University Gil Hospital Division of hematology-Oncology Department of Internal MedicineDankook University College of Medicine

AIM: To assess the efficacy and safety of weekly docetaxel plus a fixed-dose rate(FDR) of gemcitabine in metastatic esophageal squamous cell carcinoma(SCC).METHODS: A multi-center, open-label, prospective phase Ⅱ study was ***-three esophageal SCC patients with documented progression after fluoropyrimidine/platinum-based first-line chemotherapy were enrolled and treated with docetaxel 35 mg/m2 and gemcitabine 1000 mg/m2 iv at a FDR(10 mg/m2 per minute) on days 1 and *** was repeatedevery twenty-one days until disease progression, unacceptable toxicity, or consent *** primary endpoint was response rate(RR), and secondary endpoints were safety, progression-free survival(PFS) and overall survival(OS).RESULTS: Combination of weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia(97%), fatigue(64%) and neutropenia(55%).One patient with multiple lung and lymph node metastases died of respiratory failure after receiving four cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely *** control(objective response plus stable disease) in the ITT population was achieved in 88% of patients, and the overall RR was 30%(95%CI: 15%-46%).The median PFS and OS were 4.0(95%CI: 3.4-4.6) and 8.8 mo(95%CI: 7.8-9.8 mo), ***: A combination of weekly docetaxel and FDR gemcitabine showed promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC.

关键词： Clinical trial Phase Ⅱ Chemotherapy Carcinoma,Esop

Natural killer cell homing and trafficking in tissues and tumors:from biology to application

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Signal Transduction and Targeted therapy 2022年第7期7卷 2448-2468页

作者： Guang he Ran Yu qing Lin Lei Tian Tao Zhang Dong mei Yan Jian hua Yu You cai Deng Department of Immunology School of Basic MedicalJiamusi University154007 JiamusiChina Institute of Materia Medica College of PharmacyArmy Medical University400038 ChongqingChina Department of hematology and Hematopoietic cell Transplantation City of Hope National Medical CenterLos AngelesCA 91010USA Department of Clinical hematology College of PharmacyArmy Medical University400038 ChongqingChina

Natural killer(NK)cells,a subgroup of innate lymphoid cells,act as the first line of defense against *** some evidence shows that NK cells can develop in secondary lymphoid tissues,NK cells develop mainly in the bone marrow(BM)and egress into the blood circulation when they *** then migrate to and settle down in peripheral tissues,though some special subsets home back into the BM or secondary lymphoid *** to its success in allogeneic adoptive transfer for cancer treatment and its“off-the-shelf”potential,NK cell-based immunotherapy is attracting increasing attention in the treatment of various ***,insufficient infiltration of adoptively transferred NK cells limits clinical utility,especially for solid *** of NK cells or engineered chimeric antigen receptor(CAR)NK cells ex vivo prior to adoptive transfer by using various cytokines alters the profiles of chemokine receptors,which affects the infiltration of transferred NK cells into tumor *** factors control NK cell trafficking and homing,including cell-intrinsic factors(e.g.,transcriptional factors),cell-extrinsic factors(e.g.,integrins,selectins,chemokines and their corresponding receptors,signals induced by cytokines,sphingosine-1-phosphate(S1P),etc.),and the cellular ***,we summarize the profiles and mechanisms of NK cell homing and trafficking at steady state and during tumor development,aiming to improve NK cell-based cancer immunotherapy.

关键词： killer organs transferred