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造血干细胞移植 2

供体来源的CD19靶向T细胞输注 1

共病指数 1

单倍体 1

巨噬细胞 1

微小残留病 1

急性B淋巴细胞白血病 1

排斥反应 1

疾病风险共病指数 1

疾病风险指数 1

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Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

《医学前沿（英文）》 2021年 第15卷 第1期   页码 108-115 doi: 10.1007/s11684-019-0730-8

摘要： Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group ( =0.03 and =0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词： post-transplantation cyclophosphamide     allogeneic hematopoietic stem cell transplantation     lymphoid malignancies    

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Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell

《医学前沿（英文）》 2022年 第16卷 第6期   页码 957-968 doi: 10.1007/s11684-021-0910-1

摘要： Skin and soft tissue infections (SSTIs) refer to infections involving the skin, subcutaneous tissue, fascia, and muscle. In transplant populations with hematological malignancies, an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly. However, to date, the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation (HSCT) patients remain unclear. This study included 228 patients (3.67%) who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital. The overall annual survival rate was 71.5%. We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure (PPGF), comorbidities of acute kidney injury (AKI), and hospital-acquired pneumonia (HAP) were independent risk factors for death in the study population. A PPGF–AKI–HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP. The areas under the curves of internal and external validation were 0.833 (95% CI 0.760–0.906) and 0.826 (95% CI 0.715–0.937), respectively. The calibration plot revealed the high consistency of the estimated risks, and decision curve analysis showed considerable net benefits for patients.

关键词： skin and soft tissue infections     hematopoietic stem cell transplantation     risk stratification system     mortality    

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Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 304-311 doi: 10.1007/s11684-015-0400-4

摘要：

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 allo-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 allo-HSCT group. Multivariate analysis showed that male sex and TKI2therapy 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 patients with CML in accelerated phase.

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

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Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed

《医学前沿（英文）》 2021年 第15卷 第5期   页码 728-739 doi: 10.1007/s11684-021-0833-x

摘要： 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 studies. However, 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 center. With a median follow-up of 918 (457–1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The 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, respectively. Risk 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 post-HSCT2. Our 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    

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syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

《医学前沿（英文）》 2019年 第13卷 第2期   页码 238-249 doi: 10.1007/s11684-017-0599-3

摘要： 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) ( =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    

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Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 354-364 doi: 10.1007/s11684-018-0665-5

摘要： The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon- (IFN- ) 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 allo-HSCT were studied ( =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 sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% ( =0.377) and 9.1% and 0.0% ( =0.985) for patients in the IFN- and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% ( =0.891) and 84.3% and 84.6% ( =0.972) for patients in the IFN- and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN- treatment.

关键词： donor leukocyte infusion     hematopoietic stem cell transplantation     interferon-   

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Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 306-315 doi: 10.1007/s11684-013-0279-x

摘要：

Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective options for hematological malignancies, and human leukocyte antigen-partially matched related donors (PMRDs) are a valuable option for HSCT. Several protocols (with or without ex vivo T-cell depletion (TCD)) have been established worldwide. TCD including CD34+positive selection and CD3/CD19 depletion has successfully overcome the human leukocyte antigen disparity. However, TCD is associated with prolonged immune deficiencies, increased risks of infectious complications, and high transplantation-related mortality. PMRD HSCT without ex vivo TCD is well developed, and numerous patients have benefitted from it. Here, we review the literature on PMRD HSCT.

关键词： partially matched related donor     hematopoietic stem cell transplantation     allogeneic    

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巨噬细胞在器官移植急性排斥反应中的双重作用 Review

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

《工程（英文）》 2022年 第10卷 第3期   页码 21-29 doi: 10.1016/j.eng.2021.10.015

摘要：

天然免疫细胞在移植免疫反应中发挥着重要作用。巨噬细胞是重要的天然免疫细胞；在发生排斥反应的同种异基因移植器官中，巨噬细胞也是浸润的众多免疫细胞之一。巨噬细胞的浸润与器官移植的短期和长期效果呈负相关。在功能方面，巨噬细胞具有异质性和可塑性。在器官移植排斥反应中，巨噬细胞可以为适应性免疫提呈同种异基因抗原以及提供共刺激信号和细胞因子，也可以直接损伤移植器官。此外，一些具有免疫调节功能的巨噬细胞亚群，可以通过抑制排斥反应和促进免疫耐受来保护移植器官。尽管目前研究人员已认识到巨噬细胞在移植器官损伤过程中的潜在作用，但他们对巨噬细胞在移植排斥反应中的不同作用关注不够。为此，本文就巨噬细胞在急性移植免疫反应中的独特作用以及免疫抑制剂对巨噬细胞的影响进行了综述和讨论。通过分析发现，对于巨噬细胞在移植免疫中的作用的相关研究中，应更多地关注其复杂性和关键功能，并应更多地致力于开发针对巨噬细胞的免疫抑制药物，并使之有利于提高移植器官的长期存活率和移植免疫耐受的建立。

关键词： 巨噬细胞     移植     耐受     排斥反应     调节性巨噬细胞    

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疾病危险度-共患病指数在单倍型造血干细胞移植中的应用 Article

莫晓冬, 张晓辉, 许兰平, 王昱, 闫晨华, 陈欢, 陈育红, 韩伟, 王峰蓉, 王景枝, 刘开彦, 黄晓军

《工程（英文）》 2021年 第7卷 第2期   页码 162-169 doi: 10.1016/j.eng.2020.12.005

摘要：

本文的研究目的是基于疾病危险度指数（disease risk index, DRI）和造血干细胞移植共患病指数（hematopoietic cell transplantation-specific comorbidity index, HCT-CI），提出适合单倍型造血干细胞移植（haploidentical hematopoietic stem cell transplantation, haplo-HSCT）患者的疾病危险度-共患病指数（disease risk comorbidity index, DRCI）。文中通过一个训练队列（n = 593）中确定了无疾病生存（disease-free survival, DFS）的预测因素，然后对这些因素进行赋值，从而建立DRCI，并通过验证队列（n = 296）检验积分系统的有效性。多因素分析确定了DFS的两个独立影响因素：移植前DRI以及HCT-CI。我们为极高危DRI赋值2分，为高危DRI和中、高危HCT-CI各赋值1分，从而形成适合haplo-HSCT的DRCI（即haplo-DRCI）。在验证队列中，低危、中危、高危组患者移植后3年的累积DFS率分别为65.2％ (95％CI, 58.2％~72.2％)、55.8％ (95％CI, 44.9％~66.7％)和32.0％ (95％CI, 5.8％~58.2％) (P = 0.005)。Haplo-DRCI 还可以预测不同疾病亚组，尤其是急性白血病患者移植后的DFS。此外，在独立的历史队列中 (n = 526)，较高的haplo-DRCI积分同样与较高的复发率、较高的非复发死亡率（non-relapse mortality, NRM）、较差的DFS率和较差的总体生存率（overall survival, OS）相关。这些结果表明，haplo-DRCI积分可以有效地对接受haplo-HSCT的患者进行危险分层，更好地预测哪些患者更能获益于haplo-HSCT。

关键词： 疾病风险指数     疾病风险共病指数     造血细胞移植     共病指数     造血干细胞移植     单倍体    

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供体来源的CD19靶向T细胞输注可以消除异基因造血干细胞移植后对供者淋巴细胞无反应的急性B淋巴细胞白血病微小残留病 Article

程翼飞, 陈育红, 闫晨华, 王昱, 赵翔宇, 陈瑶, 韩伟, 许兰平, 张晓辉, 刘开彦, 王莎莎, 张隆基, 肖磊, 黄晓军

《工程（英文）》 2019年 第5卷 第1期   页码 150-155 doi: 10.1016/j.eng.2018.12.006

摘要：

白血病复发仍是异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后急性B 淋巴细胞白血病（B cell

关键词： 供体来源的CD19靶向T细胞输注     造血干细胞移植     急性B淋巴细胞白血病     微小残留病    

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标题 作者 时间 类型 操作

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

期刊论文

Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell

期刊论文

Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult

null

期刊论文

Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed

期刊论文

syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

期刊论文

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

期刊论文

Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation

null

期刊论文

巨噬细胞在器官移植急性排斥反应中的双重作用

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

期刊论文

疾病危险度-共患病指数在单倍型造血干细胞移植中的应用

莫晓冬, 张晓辉, 许兰平, 王昱, 闫晨华, 陈欢, 陈育红, 韩伟, 王峰蓉, 王景枝, 刘开彦, 黄晓军

期刊论文

供体来源的CD19靶向T细胞输注可以消除异基因造血干细胞移植后对供者淋巴细胞无反应的急性B淋巴细胞白血病微小残留病

程翼飞, 陈育红, 闫晨华, 王昱, 赵翔宇, 陈瑶, 韩伟, 许兰平, 张晓辉, 刘开彦, 王莎莎, 张隆基, 肖磊, 黄晓军

期刊论文