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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

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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

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Novel agents targeting leukemia cells and immune microenvironment for prevention and treatment of relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2125-2139页

作者： Wei Shi Weiwei Jin Linghui Xia Yu Hu Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Fred Hutchinson Cancer Research Center SeattleWA 98109-1024USA Department of Cardiovascular Optical Valley School DistrictHubei Provincial Hospital of Traditional Chinese MedicineWuhan 430061China Hubei Province Academy of Traditional Chinese Medicine Wuhan 430074China

Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically *** the rapid development of genomics and immunotherapies,the interference strategies for AML recurrence have been changing these *** and more novel targeting agents that have received the *** and Drug Administration(FDA)approval for de novo AML treatment have been administrated in the salvage or maintenance therapy of post-HSCT *** strategies that regulate the immune microenvironment of and optimize the graft versus leukemia(GVL)effect of immune cells are gradually *** agents not only have been proven to achieve clinical benefits from a single drug,but if combined with classic therapies,can significantly improve the poor prognosis of AML patients who relapse after *** review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.

关键词： AML Targeted therapy Relapse Immune microenvironment allogeneic hematopoietic stem cell transplantation Oncogenic effectors Metabolism Surface markers

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Gut microbiome in allogeneic hematopoietic stem cell transplantation and specific changes associated with acute graft vs host disease

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World Journal of Gastroenterology 2021年第45期27卷 7792-7800页

作者： Quentin Le Bastard Patrice Chevallier Emmanuel Montassier Department of Emergency Medicine Nantes University HospitalNantes 44093France Department of Hematology Nantes University HospitalNantes 44093France

allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological ***,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease *** if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT ***,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.

关键词： Gut microbiome DNA sequencing technologies allogeneic hematopoietic stem cell transplantation Transplants Acute graft vs host disease Biomarkers Composition Function

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Clinical and serological characterization of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation

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Chinese Medical Journal 2014年第7期127卷 1235-1238页

作者： Yang Zhen Wu Bangzhao Zhou Youning Wang Wenjuan Chen Suning Sun Aining Wu Depei Xu Yang Jiangsu Institute of Hematology Key laboratory of Thrombosis and Hemostasis Ministry of Health The First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China

Background Autoimmune hemolytic anemia （AIHA） is an uncommon complication of allogeneic hematopoietic stem cell transplantation （allo-HSCT） which has only been reported in a few *** here aimed to explore its *** We retrospectively analyzed 296 patients who underwent allo-HSCT in our center from July 2010 to July *** manifestations were carefully reviewed and the response to currently available treatment approaches were *** survival and risk factors of AIHA patients after allo-HSCT were further *** Twelve patients were diagnosed with AIHA at a median time of 100 days （15-720 days） after *** incidence of AIHA after allo-HSCT was 4.1％.IgG antibody were detected in ten patients and IgM antibody in two *** two cold antibody AIHA patients had a better response to steroid corticoid only treatment and the ten warm antibody AIHA patients responded to corticosteroid treatment and adjustment of immunosuppressant *** was shown to be effective for AIHA patients who failed conventional *** analysis showed that the combination of AIHA in allo-HSCT patients hinted at poor *** （CMV） infection,graft-versus-host disease （GVHD） and histocompatibility leukocyte antigen （HLA） mismatch seemed to increase the risk of developing *** Patients who develop AIHA after allo-HSCT have poor survival compared to non-AIHA *** risk factors of AIHA are CMV infection,GVHD,and HLA *** is likely to be the effective treatment choice for the refractory patients.

关键词： autoimmune hemolytic anemia allogeneic hematopoietic stem cell transplantation graft-versus-host disease

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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

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Ex vivo expansion of regulatory T cells for clinical applications against graft-versus-host disease in allogeneic hematopoietic stem cell transplantation

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Chinese Medical Journal 2013年第23期126卷 4575-4582页

作者： ZHANG Lan-fang XIA Chang-qing Department of Hematology Xuanwu Hospital Capital Medical University Beijing 100053 China

Objective To review the characteristics of regulatory T cells （Tregs） and ex vivo expansion of Tregs for treatment of graftversus-host disease （GVHD）.Data sources The data used in this review were retrieved from PubMed （1970-2013）.The terms ＂ex vivo expansion＂,＂regulatory T cell＂,and ＂graft-versus-host disease＂ were used for literature *** selection The publications about the characteristics of Tregs,ex vivo expansion of Tregs and clinical applications of Tregs against GVHD were identified,retrieved and *** Tregs can be classified as natural Tregs （nTregs） and induced Tregs （iTregs）.Both subsets share most Treg *** their immunosuppressive property,Tregs have been tested for their capability of preventing *** bottleneck of Treg therapy is the limited numbers of naturally existing *** solve this problem,ex vivo expansion of nTregs or iTregs has been *** initial data indicate Treg therapy is effective in reducing GVHD without compromising graft-versus-leukemia （GVL）.Conclusion Ex vivo expansion of Tregs is a reliable way to prepare sufficient number of Tregs for management of GVHD.

关键词： ex vivo expansion regulatory T cells adoptive therapy graft-versus-host disease allogeneic hematopoietic stem cell transplantation

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Graft-versus-leukemia effects of Wilms＇ tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

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Chinese Medical Journal 2010年第7期123卷 912-916页

作者： WANG Zhi-dong LI Dan HUANG Xiao-jun Institute of Hematology Peking University People's HospitalBeijing 100044 China

Background The role of Wilms＇ tumor 1 protein （WT1）-specific cytotoxic T cells （CTL） in eradicating chronic myeloid leukemia （CML） cells is to be established. The aim of this study was to determine whether WT1 contributed to the graft-versus-leukemia effects （GVLE） for CML following allogeneic hematopoietic stem cell transplantation （HSCT）. Methods High-resolution human leukocyte antigen （HLA） class I genotyping was performed by sequence-specific polymerase chain reaction （PCR）. Fifteen HLA-A~＊2402 patients with CML who underwent allogeneic HSCT were enrolled in this study. We monitored the frequency of WT1-specific CTL by pentamer assay and the molecular minimal residual disease by real-time quantitative *** A CD8＋ T-cell response to WT1 was observed in 14 of 15 patients after HSCT. The median frequencies of WT1-CTL were 0.54%, 0.62%, 0.81% and 1.28% （%CD8） on days 30, 60, 90 and 180, respectively. The median frequency of WT1-CTL （1.38%） in patients with molecular remission （MoR） was significantly higher than that in those without MoR （0.38%） on day 30, while no significant differences between them were detected on days 60, 90 and 180. The increase of WT1-CTL was associated with a decrease in bcr-abl expression and MoR; and the decrease of WT1-CTL was associated with an increase in bcr-abl expression, suggesting a WT1 -driven GVL effect. WT1-CTL had a predominant effector-memory phenotype （CD45RO＋CD27-CD57＋）.Conclusions The emergence of WT1-CTL with an effector-memory phenotype is associated with GVLE in CML patients after HSCT. This will pave the way for the WT1 vaccines to enhance GVLE after HSCT in CML.

关键词： cytotoxic T cells Wilms' tumor 1 protein graft-versus-leukemia effects chronic myeloid leukemia allogeneic hematopoietic stem cell transplantation

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Profiles of interferon-gamma and interleukin-2 in patients after allogeneic hematopoietic stem cell transplantation

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World Journal of Biological Chemistry 2022年第4期13卷 72-82页

作者： Malwina Rybicka-Ramos Mirosław Markiewicz Aleksandra Suszka-Świtek Ryszard Wiaderkiewicz Sylwia Mizia Monika Dzierżak-Mietła Krzysztof Białas Department of Hematology Specialist Hospital No.1 in BytomBytom 41-902Poland Department of Hematology University of RzeszowCollege of Medical SciencesInstitute of Medical SciencesRzeszów 35-315Poland Department of Histology and Embryology School of Medicine in KatowiceMedical University of SilesiaKatowice 40-752Poland Department of Population Health Division of Epidemiology and Health EducationWroclaw Medical UniversityWrocław 51-618Poland Department of Bone Marrow transplantation and Hematooncology Maria Sklodowska-Curie National Research Institute of OncologyGliwice 44-102Poland Department of Hematology and Bone Marrow transplantation SPSK-M HospitalKatowice 40-027Poland

BACKGROUND allogeneic hematopoietic stem cell transplantation(allo-HSCT)may be related to the occurrence of complications,including graft-versus-host disease(GvHD)and *** pathogenesis of acute GvHD is connected with T lymphocytes,which identify alloantigens on host's antigen-presenting cells,activate production of interferon-gamma(IFN-gamma)and interleukin-2(IL-2),and act on the immune effector cells and damage tissues and *** The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after *** We enrolled 62 patients,i.e.,30(48%)male and 32(52%)female subjects[median age 49.5(19-68)years],after allo-HSCT from siblings(n=12)or unrelated donors(n=50)due to acute myeloid leukemia with myeloablative conditioning(n=26;42%)and with non-myeloablative conditioning(n=36;58%).All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated *** samples were collected pre-transplant before and after(on day-1)the conditioning therapy and on days+2,+4,+6,+10,+20,and+30 after *** levels of IL-2 and IFNgamma were determined using *** Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of *** I included patients with neither acute GvHD nor infections[n=15(24%)],group II consisted of patients with infections without acute GvHD[n=17(27%)],group III was comprised of patients with acute GvHD without infections[n=9(15%)],and group IV included patients with both acute GvHD and infections[n=21(34%)].IFN-gamma concentrations were higher in Group II than in other groups on days+20(P=0.014)and+30(P=0.008).Post-hoc tests showed lower concentrations of IFN-gamma on day+30 in groups I(P=0.039)and IV(P=0.017)compared to group *** levels of IL-2 were mostly *** Serum levels of IFN-gamma fol

关键词： Interleukin-2 Interferon-gamma Cytokine profiles Acute myeloid leukemia allogeneic hematopoietic stem cell transplantation Acute graft-versus-host disease

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

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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 *** study aimed to analyze risk factors of HC and its effect on patient *** collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August *** 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 *** used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC *** also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve(ROC)*** propensity score matching,there were 131 patients each in the HC and non-HC *** 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)*** 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 ***,CMV(urine),and BKV(urine)were independent risk factors for HC based on the multivariate *** 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%,*** analysis indicated that a urine BKV load of 1×10^(7) copies/mL was able to stratify the risk of *** conclusion,when the BKV load is>1×10^(7),we needtobe aware of the potential for

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

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