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Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

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Chinese Medical Journal 2024年第4期137卷 478-480页

作者： Wei Sun Yuanyuan Zhang Yuhong Chen Yuqian Sun Yifei Cheng Fengrong Wang Huan Chen Yao Chen chenhua yan Xiaodong Mo Wei Han Lanping Xu Yu Wang Xiaohui Zhang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking UniversityBeijing 10004China

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological ***,allo-HSCT treatment can cause serious ***-transplant kidney damage is an important *** this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

关键词： hematopoietic clinical matched

Modification of donor lymphocyte infusion: how to improve the outcome?

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Science China(Life Sciences) 2019年第9期62卷 1253-1256页

作者： Yu Wang Lanping Xu chenhua yan Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Beijing 100871China

(HSCT),which has been acknowledged as a curative procedure,relapse of leukemia remains the leading cause of death following transplantation and is a disappointment to transplant *** relapse occurs due to leukemia cell escape from immune-mediated killing (immune escape) by pre-transplantation conditioning and post-transplantation immune *** exhaustion of donor T cells is one of the common causes of relapse,and donor lymphocyte infusions (DLIs) have the potential to reverse this immune *** who are deemed eligible for intensive treatment at this point are offered either DLI or a second *** to the contemporary understanding,DLI results in the same response and survival obtained via a second transplant but with less toxicity (Kharfan- Dabaja et al.,2018).Starting in the mid-1990s,our group along with few others demonstrated the efficacy of DLI,which was initially confirmed by the Hadassah group in Jerusalem in the late *** the first four patients (with both acute and chronic leukemias) treated by us with DLI,the initial success rate was 100%,which encouraged us to pursue this treatment further.

关键词： intensive treatment escape from along with

血液病患者异基因造血干细胞移植后粒细胞植入前死亡原因分析

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中华血液学杂志 2024年第6期45卷 542-548页

作者：刘竞吕萌张圆圆莫晓冬孙于谦闫晨华王昱许兰平张晓辉刘开彦黄晓军北京大学人民医院北京大学血液病研究所国家血液系统疾病临床医学研究中心造血干细胞移植治疗血液病北京市重点实验室北京100044

目的:分析异基因造血干细胞移植(allo-HSCT)患者粒细胞植入前死亡原因及人群特征。方法:对2016年1月至2023年7月在北京大学人民医院行allo-HSCT的全部7427例患者进行回顾性分析。结果:7427例患者中有56例(0.75%)在中性粒细胞植入前死亡... 详细信息

目的:分析异基因造血干细胞移植(allo-HSCT)患者粒细胞植入前死亡原因及人群特征。方法:对2016年1月至2023年7月在北京大学人民医院行allo-HSCT的全部7427例患者进行回顾性分析。结果:7427例患者中有56例(0.75%)在中性粒细胞植入前死亡,中位死亡时间为+7 d(-3 d~+38 d)。急性白血病(AL)、重型再生障碍性贫血(SAA)、骨髓增生异常综合征(MDS)患者的中位死亡时间分别为+11 d(-1 d~+38 d)、+3 d(-1 d~+34 d)、+16 d(-1 d~38 d)(P=0.013)。主要死亡原因为感染(39.3%)、预处理心脏毒性(28.6%)和颅内出血(26.8%)。感染是引起AL和MDS患者最常见的死亡原因(55.0%、60.0%)。预处理心脏毒性所致死亡主要见于SAA患者(71.4%),而在AL患者中未见到,MDS中仅1例。53.3%的颅内出血死亡患者合并严重感染。感染、预处理心脏毒性、颅内出血引起植入前死亡的中位时间分别是+11 d(-1 d~+38 d)、+2.5 d(-1 d~+17 d)、+8 d(-3 d~+37 d)(P<0.001)。结论:感染是allo-HSCT患者粒细胞植入前死亡的主要原因,SAA患者应关注严重心脏毒性导致的植入前死亡。

关键词：异基因造血干细胞移植移植相关死亡死亡原因感染心脏毒性

Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed acute leukemia post-chemotherapy plus modified donor lymphocyte infusion

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Frontiers of Medicine 2021年第5期15卷 728-739页

作者： Tingting Han Yuqian Sun yang Liu chenhua yan Yu Wang Lanping Xu Kaiyan Liu Xiaojun Huang Xiaohui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China Collaborative Innovation Center of Hematology Peking UniversityBeijing 100044China Peking-Tsinghua Center for Life Sciences Beijing 100044China

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation(allo-HSCT).The outcome of a second allo-HSCT(HSCT2)for relapse post-HSCT has shown promising results in some previous ***,little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia(AL)post-chemotherapy plus modified donor lymphocyte infusion(post-Chemo+m-DLI)after the first allo-HSCT(HSCT1).Therefore,we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo+m-DLI in our *** a median follow-up of 918(457–1732)days,26 patients(92.9%)achieved complete remission,and 2 patients exhibited persistent *** probabilities of overall survival(OS)and disease-free survival(DFS)1 year after HSCT2 were 25.0%and 21.4%,*** cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1%±4.9%and 25.0%±8.4%.The cumulative incidences of relapse were 50.0%±9.8%and 53.5%±9.9%at 1 and 2 years post-HSCT2,*** stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2,and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse *** findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo+m-DLI.

关键词： second hematopoietic stem cell transplantation acute leukemia relapse chemotherapy modified donor lymphocyte infusion

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

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Frontiers of Medicine 2019年第3期13卷 354-364页

作者： Xiaodong Mo Xiaohui Zhang Lanping Xu Yu Wang chenhua yan Huan Chen Yuhong Chen Wei Han Fengrong Wang Jingzhi Wang Kaiyan Liu Xiaojun Huang Peking University People's Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Centerfor Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100044China

The efficacy of minimal residual disease (MRD)-directed immunotherapy,including interferon-α (IFN-α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI),was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT).High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after ailo-HSCT were studied (n =47).The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow *** cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P=0.377)and 9.1% and 0.0% (P=0.985) for patients in the IFN-α and chemo-DLI groups,*** probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P =0.891) and 84.3% and 84.6% (P=0.972) for patients in the IFN-α and chemo-DLI groups,*** MRD after immunotherapy was associated with poor ***,the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after alIo-HSCT,and the efficacy was comparable between chemo-DLI and IFN-α treatment.

关键词： donor leukocyte infusion hematopoietic stem cell transplantation interferon-α minimal residual disease myelodysplastic syndrome

Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem cell transplantation

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Frontiers of Medicine 2019年第4期13卷 492-503页

作者： Lijuan Hu Qi Wang Xiaohui Zhang Lanping Xu Yu Wang chenhua yan Huan Chen Yuhong Chen Kaiyan Liu Hui Wang Xiaojun Huang Xiaodong Mo Peking University People's Hospital Peking University Institute of Hematology Beijing 100044 China Peking- Tsinghua Center for Lifs Sciences Beijing 100044 China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044 China Peking University People's Hospital Department of Clinical Laboratory Beijing 100044 China

We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT)(n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group;19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens .

关键词： haploidentical hematopoietic stem cell transplantation stool culture Candida

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation

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Frontiers of Medicine 2019年第2期13卷 238-249页

作者： Xiaodong Mo Xiaohui Zhang Lanping Xu Yu Wang chenhua yan Huan Chen Yuhong Chen Wei Han Fengrong Wang Jingzhi Wang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100044China

The efficacy of salvage interferon-α(IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI)(n=24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.

关键词： interferon-α hematopoietic stem cell transplantation minimal residual disease donor lymphocyte infusion

Risk factors for chronic graft-versus-host disease after anti-thymocyte globulin-based haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia

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Frontiers of Medicine 2019年第6期13卷 667-679页

作者： Meng Lv Xiaohui Zhang Lanping Xu Yu Wang chenhua yan Huan Chen Yuhong Chen Wei Han Fengrong Wang Jingzhi Wang Kaiyan Liu Xiaojun Huang Xiaodong Mo Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100044China

Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia(n=280).The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria.A total of 169 patients suffered from *** patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD(total,66.0%vs.53.7%,P=0.031;moderate to severe,42.4%vs.30.1%,P=0.036)than the patients who had 1 to 2 loci *** patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD(49.2%vs.32.9%,P=0.024)compared with the patients who had other *** patients who had grades III to IV acute GVHD(aGVHD)had higher 8-year incidence of cGVHD(total,88.0%vs.50.4%,P<0.001;moderate to severe,68.0%vs.27.0%,P<0.001)compared with the patients without *** multivariate analysis,grades III to IV aGVHD was the only independent risk factor for ***,further interventions should be considered in patients with severe aGVHD to prevent cGVHD.

关键词： acute graft-versus-host disease chronic graft-versus-host disease National Institutes of Health consensus criteria acute myeloid leukemia anti-thymocyte globulin

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

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Engineering 2019年第1期5卷 150-155页

作者： Yifei Cheng Yuhong Chen chenhua yan Yu Wang Xiangyu Zhao Yao Chen Wei Han Lanping Xu Xiaohui Zhang Kaiyan Liu Shasha Wang Lungji Chang Lei Xiao Xiaojun Huang Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Peking University Institute of Hematology Peking University People’s Hospital Beijing 100044 China Collaborative Innovation Center of Hematology Peking University Beijing 100084 China Shenzhen Geno-Immune Medical Institute Shenzhen 518057 China Innovative Cellular Therapeutics Co. Ltd. Shanghai 201499 China

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

关键词： Donor-derived CD19-targeted T cell infusion Hematopoietic stem cell transplantation B cell acute lymphoblastic leukemia Minimal residual disease