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Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneicperipheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm

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    

Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients

《医学前沿(英文)》 2023年 第17卷 第1期   页码 58-67 doi: 10.1007/s11684-022-0937-y

摘要: The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65–70 years (111 recipients, group 65–70) and 70 years (55 recipients, group 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group 70 (30.9% vs. 14.4% in group 65–70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65–70) and 7.3% (group 70) of patients. Kaplan–Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.

关键词: cardiac disease     mortality     aged population     lung transplantation    

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

《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    

Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

SUN Ledong, SUN Jing, ZENG Kang, MENG Fanyi, DIAO Youtao, XU Dan, HUANG Liang, ZHAO Jie, Liu Qifa

《医学前沿(英文)》 2008年 第2卷 第2期   页码 191-194 doi: 10.1007/s11684-008-0036-8

摘要: The aim of this study is to explore the effectiveness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus. A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities. The diagnosis of pemphigus was made on the basis of the clinical, histologic and immunofluorescence findings. The patient had shown resistance to conventional therapy with glucocorticoid and immunosuppressive agents. Two months before admission, he complained of hip joint pain. X-ray and CT scan revealed aseptic necrosis of the femoral head. Stem-cell mobilization was achieved by treatment with cyclophosphamide, granulocyte colony-stimulating factor (G-CSF) and rituximab. Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use. Immunoablation was accomplished by using cyclophosphamide (200 mg/kg; divided into 50 mg/kg on days -5, -4, -3, and -2), antithymocyte globulin (ATG; 10 mg/kg; divided into 2.5 mg/kg on days -6, -5, -4, and -3), and rituximab (1200 mg/d; divided into 600 mg/d on days 0 and 7). Autologous peripheral hematopoietic stem cell transplantation was followed by reconstitution of the immune system which was monitored by flow cytometry. The glucocorticoid was withdrawn immediately after transplantation. The pemphigus titer turned negative 6 weeks after transplantation and remained negative. The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of follow-up. The patient’s response suggests that autologous peripheral hematopoietic stem cell transplantation may be a potential “cure” for refractory pemphigus. However, further studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resistance to conventional therapy.

关键词: serological activity     leukapheresis     peripheral hematopoietic     cyclophosphamide     resistance    

Treatment of gingival hyperplasia induced by cyclosporine A

MA Jingzhi, LI Ming, CAO Yingguang

《医学前沿(英文)》 2008年 第2卷 第3期   页码 290-294 doi: 10.1007/s11684-008-0055-5

摘要: The clinical therapy for cyclosporine A (CsA)-induced gingival hyperplasia (GH) and the pathological changes in hyperplastic gingival tissues were investigated. Nine cases of CsA-induced GH after renal transplantation were subjected to periodontal non-surgical treatment and surgical treatment and were followed up. Gingival index (GI), dental plaque index (PLI) and GH degree (GHD) at different time points were measured. Under light and electron microscopy, the pathological changes in hyperplastic gingival tissues were observed. The CsA concentrations in gingival tissues and blood were determined by using fluorescence polarization immunoassay with TDFL monoclonal antibody. The results showed that GI, PLI and GHD in patients with GH declined after periodontal treatment. Two patients suffered from different degrees of GH during the 6 months to 54 months post-transplantation. Under transmission electron microscopy, fibroblasts in the hyperplastic gingival tissues were enlarged, cytoplasmic rough endoplasmic reticula were abundant and expanded slightly, and a few fibroblasts with early apoptotic changes were seen. The concentrations of CsA in hyperplastic gingival tissues were from 351.00 to 1345.47 ng/mL, which were significantly higher than in the blood of the same patients taken at the same time points. It was concluded that GI and PLI declined after periodontal treatment in combination with surgical treatment in patients taking CsA for a long time, but in some patients, GH recurred. The fact that the concentration of CsA in hyperplastic gingival tissues is higher than in blood awaits further studies.

关键词: post-transplantation     Gingival     cytoplasmic     CsA-induced     further    

肝内区域免疫对肝移植后肿瘤复发的影响 Review

刘江, 卢宠茂, 万钧

《工程(英文)》 2022年 第10卷 第3期   页码 57-64 doi: 10.1016/j.eng.2021.11.012

摘要:

肝脏恶性肿瘤是肝移植的一个主要适应症,但是肝移植后肿瘤复发却是影响受体长期生存的一个严峻临床挑战。肿瘤生物学特征、分期和移植后的免疫抑制状态一直被认为是肝癌复发的危险因素。而越来越多的证据表明,肝脏缺血再灌注(IR)对同种异体移植物的损伤则为肝移植后的肿瘤细胞侵袭性、转移性
提供了有利的免疫微环境。在活体肝移植中,边缘移植物(如小体积或脂肪移植物)的严重损伤与较低的无复发生存率之间的相关性,证实了IR 损伤与肿瘤复发之间的关联。IR 可引起肝内免疫微环境重构,包括恶化移植物损伤的促炎反应和加快组织修复的抗炎反应。然而,肝内区域免疫对移植后肿瘤复发的作
用尚不清晰。本文详述了IR 损伤诱导的肝内体液微环境和调节性区域免疫微环境,以及它们如何影响肝移植后肿瘤复发的最新研究进展。综合理解移植后肝内区域免疫,将为移植后肿瘤复发提供精准诊断、治疗和预后预测的新策略。

关键词: 肝移植     肝癌     复发     免疫学    

Partial liver transplantation

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 1-7 doi: 10.1007/s11684-010-0105-7

摘要:

Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.

关键词: partial liver transplantation     reduced-size liver transplantation     split liver transplantation     living donor liver transplantation    

Successful kidney transplantation in highly sensitized patients

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 80-85 doi: 10.1007/s11684-011-0115-0

摘要:

Highly sensitized patients experience an increased number of rejection episodes and have poorer graft survival rates; hence, sensitization is a significant barrier to both access to and the success of organ transplantation. This study reports our experience in kidney transplantation in highly sensitized patients. Fourteen patients with sensitization or high levels of panel-reactive antibodies (PRA) were studied. All patients were desensitized with pre-transplant intravenous immunoglobulin (IVIG)/plasmapheresis (PP) with or without rituximab and thymoglobulin induction therapy, combined with a Prograf/MMF/Pred immunosuppressive regimen. Of 14 patients, 10 showed good graft functions without acute rejection (AR) episodes. Acute cellular rejection in two patients was reversed by methylprednisolone. Two patients underwent antibody-mediated rejection; one was treated with PP/IVIG successfully, whereas the other lost graft functions due to the de novoproduction of donor-specific antibodies (DSA). Graft functions were stable, and there were no AR episodes in other patients. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful live-donor kidney transplantation in sensitized recipients.

关键词: Kidney transplantation     desensitization    

Liver surgery and transplantation in China: Progress and Challenges

LAU W Y, LAI E C H

《医学前沿(英文)》 2007年 第1卷 第1期   页码 1-5 doi: 10.1007/s11684-007-0001-y

摘要: From the limited but available information, we traced the history of developments of liver surgery and transplantation in China. Liver surgery first started in the late 1950s in China, and it soon flourished mainly because of the great demand in liver surgery and the emergence of a number of giants in liver surgery. We recognized and honoured the important contributions of these Chinese pioneers in portal hypertension, recurrent pyogenic cholangitis, hepatocellular carcinoma and liver transplantation.

关键词: transplantation     pyogenic cholangitis     available information     important     hypertension    

Efficacy and safety of JAK inhibitor INC424 in patients with primary and post-polycythemia vera or post-essential

null

《医学前沿(英文)》 2016年 第10卷 第4期   页码 437-443 doi: 10.1007/s11684-016-0472-9

摘要:

A phase II study (A2202) was performed to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in 63 Chinese MF patients. Ruxolitinib was given twice a day (bid) at a starting dose of 15 mg (n=25) or 20 mg (n=38) based on a baseline platelet count. About 94.7% of the patients achieved a reduction in spleen size, 27.0% of which exhibited significant reduction (≥35%) at week 24. Significant improvement in debilitating constitutional symptoms, as assessed by MFSAF v2.0, was observed in patients treated with ruxolitinib. Ruxolitinib treatment was generally well tolerated by Chinese patients. Although the treatment was associated with an increase in certain adverse events (AEs) that were established as identified risks (anemia and thrombocytopenia), these AEs were considered manageable in this clinical setting. Ruxolitinib provided substantial reductions in splenomegaly and improvements in symptoms, and was well-tolerated by Chinese patients with MF.

关键词: JAK     ruxolitinib     Chinese patients     myelofibrosis    

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

《医学前沿(英文)》 2018年 第12卷 第2期   页码 224-228 doi: 10.1007/s11684-017-0538-3

摘要:

Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.

关键词: bronchiolitis obliterans syndrome (BOS)     hematopoietic stem cell transplantation (HSCT)     lung transplantation (LTX)    

Methodologies for the establishment of an orthotopic transplantation model of ovarian cancer in mice

null

《医学前沿(英文)》 2014年 第8卷 第1期   页码 101-105 doi: 10.1007/s11684-014-0315-5

摘要:

This study used different methods to establish an animal model of orthotopic transplantation for ovarian cancer to provide an accurate simulation of the mechanism by which tumor occurs and develops in the human body. We implanted 4T1 breast cancer cells stably-transfected with luciferase into BALB/c mice by using three types of orthotopic transplantation methodologies: (1) cultured cells were directly injected into the mouse ovary; (2) cell suspension was initially implanted under the skin of the mouse neck; after tumor mass formed, the tumor was removed and ground into cell suspension, which was then injected into the mouse ovary; and (3) a subcutaneous tumor mass was first generated, removed, and cut into small pieces, which were directly implanted into the mouse ovary. After these models were established, in vivo luminescence imaging was performed. Results and data were compared among groups. Orthotopic transplantation model established with subcutaneous tumor piece implantation showed a better simulation of tumor development and invasion in mice. This model also displayed negligible response to artificial factors. This study successfully established an orthotopic transplantation model of ovarian cancer with high rates of tumor formation and metastasis by using subcutaneous tumor pieces. This study also provided a methodological basis for future establishment of an animal model of ovarian cancer in humans.

关键词: ovarian cancer     orthotopic transplantation     animal model    

Gut microbial balance and liver transplantation: alteration, management, and prediction

null

《医学前沿(英文)》 2018年 第12卷 第2期   页码 123-129 doi: 10.1007/s11684-017-0563-2

摘要:

Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

关键词: gut microbial balance     liver transplantation     ischemia–reperfusion     acute rejection    

Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death

《医学前沿(英文)》 2022年 第16卷 第5期   页码 760-765 doi: 10.1007/s11684-021-0899-5

摘要: Voluntary contribution has become the only source of donor lungs in China since 2015. To elaborate the outcomes of patients awaiting lung transplantation (LTx) after the implementation of donation after brain death, we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1, 2015 to January 1, 2021. A total of 180 patients were enrolled in the study. The median waiting time was 1.25 months. Interstitial lung disease (ILD) (103/180, 57.2%) and chronic obstructive pulmonary disease (COPD) (56/180, 31.1%) were the most common diseases in our study population. The mean pulmonary artery pressure (mPAP) of patients in the died-waiting group was higher than that of the survivors (53.29±21.71 mmHg vs. 42.11±18.58 mmHg, P=0.002). The mortality of patients with ILD (34/103, 33.00%) was nearly twice that of patients with COPD (10/56, 17.86%) while awaiting LTx (P=0.041). In the died-waiting group, patients with ILD had a shorter median waiting time than patients with COPD after being listed (0.865 months vs. 4.720 months, P=0.030). ILD as primary disease and mPAP > 35 mmHg were two significant independent risk factors for waitlist mortality, with hazard ratios (HR) of 3.483 (95% CI 1.311–9.111; P=0.011) and 3.500 (95% CI 1.435–8.536; P=0.006). Hence, LTx is more urgently needed in patients with ILD and pulmonary hypertension.

关键词: lung transplantation     donation after brain death     waitlist    

Dynamic modelling and simulation of a post-combustion CO capture process for coal-fired power plants

《化学科学与工程前沿(英文)》 2022年 第16卷 第2期   页码 198-209 doi: 10.1007/s11705-021-2057-7

摘要: Solvent-based post-combustion capture technologies have great potential for CO2 mitigation in traditional coal-fired power plants. Modelling and simulation provide a low-cost opportunity to evaluate performances and guide flexible operation. Composed by a series of partial differential equations, first-principle post-combustion capture models are computationally expensive, which limits their use in real time process simulation and control. In this study, we propose a first-principle approach to develop the basic structure of a reduced-order model and then the dominant factor is used to fit properties and simplify the chemical and physical process, based on which a universal and hybrid post-combustion capture model is established. Model output at steady state and trend at dynamic state are validated using experimental data obtained from the literature. Then, impacts of liquid-to-gas ratio, reboiler power, desorber pressure, tower height and their combination on the absorption and desorption effects are analyzed. Results indicate that tower height should be designed in conjunction with the flue gas flow, and the gas-liquid ratio can be optimized to reduce the reboiler power under a certain capture target.

关键词: CO2 capture     post-combustion capture     simulation     dominant factor    

标题 作者 时间 类型 操作

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneicperipheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm

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

期刊论文

Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients

期刊论文

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

期刊论文

Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

SUN Ledong, SUN Jing, ZENG Kang, MENG Fanyi, DIAO Youtao, XU Dan, HUANG Liang, ZHAO Jie, Liu Qifa

期刊论文

Treatment of gingival hyperplasia induced by cyclosporine A

MA Jingzhi, LI Ming, CAO Yingguang

期刊论文

肝内区域免疫对肝移植后肿瘤复发的影响

刘江, 卢宠茂, 万钧

期刊论文

Partial liver transplantation

null

期刊论文

Successful kidney transplantation in highly sensitized patients

null

期刊论文

Liver surgery and transplantation in China: Progress and Challenges

LAU W Y, LAI E C H

期刊论文

Efficacy and safety of JAK inhibitor INC424 in patients with primary and post-polycythemia vera or post-essential

null

期刊论文

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

期刊论文

Methodologies for the establishment of an orthotopic transplantation model of ovarian cancer in mice

null

期刊论文

Gut microbial balance and liver transplantation: alteration, management, and prediction

null

期刊论文

Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death

期刊论文

Dynamic modelling and simulation of a post-combustion CO capture process for coal-fired power plants

期刊论文