46例移植后淋巴组织增殖性疾病的临床和病理特点分析

目的 通过分析46例移植后淋巴组织增殖性疾病(PTLD)的临床和病理特点提高医生对本病的诊治水平。方法 收集我院诊治的PTLD患者资料，复习其临床和病理特点。结果 入组男女比例1∶1。实体器官移植(SOT)40例，异基因干细胞移植(HSCT)6例。中位年龄3岁，移植后至确诊中位时间12.5个月，HSCT患者发病明显早于SOT患者且差异有统计学意义(Z=-2.714,P=0.005)。最常见的首发症状为淋巴结肿大。23例为非结构破坏性，10例为多形性，12例为单形性，1例为经典霍奇金淋巴瘤型。EBER检测阳性41例，阴性5例。结论 PTLD是SOT或HSCT严重的并发症，多于移植后早期发生，HSCT患者术后发病明显早于SOT患者。对PTLD早期发现、早期治疗，可改善预后。     

单倍体造血干细胞移植后迟发性淋巴组织增生性疾病一例并文献复习

正移植后淋巴组织增生性疾病(posttransplant lymphoproliferative disorder,PTLD)发生于实质器官移植(solid organ transplantation,SOT)或造血干细胞移植(hematopoietic stem cell transplantation,HSCT)的一种致命性紊乱,是移植后由于进行性免疫功能降低有关而发生的淋巴组织增生性疾病,多与EB病毒感染相关~([1])。相比于SOT,HSCT后PTLD往往发生在移植后6个月之内,迟发性的PTLD极     

儿童肝移植后淋巴组织增殖性疾病合并EB病毒相关平滑肌肿瘤1例及文献复习

<正>移植后淋巴组织增殖性疾病(post-transplant lymphoproliferative disorder, PTLD)是由一组异质性淋巴细胞增殖性疾病组成的器官移植后严重并发症。EB病毒相关平滑肌肿瘤(EB virus-associated smooth muscle tumor, EBV-SMT)是与EB病毒感染相关的罕见肿瘤。     

移植后淋巴增生性疾病六例临床病理分析

目的观察移植后淋巴增生性疾病（PTLD）的临床及病理特征，提高其诊断水平。方法对6例PTLD患者进行苏木精一伊红染色和免疫组织化学Envision法染色、原位杂交及基因重排分析，并复习临床资料及随访结果。结果6例中3例为同种异体肾移植后，诊断为单形性PTLD，分别死于诊断后4、2及1个月。2例为同种异体肝移植后，1例诊断为单形性PTLD，诊断后5个月死亡。1例诊断为早期病变。另1例是异体骨髓移植后诊断为多形性PTLD，随访12个月病情较稳定，6例中4例检出EBERl／2DNA。结论PTLD是发生于器官移植后的具有独特的病理形态和临床特征的淋巴增生性疾病，其预后与病理类型及临床分期相关。     

异基因外周血造血干细胞移植后PTLD的临床分析

目的:研究异基因外周血造血干细胞移植后淋巴增殖性疾病(PTLD)的临床特点,提高对PTLD的认识和诊疗水平。方法:回顾分析于2014年5月-2017年4月在中国人民解放军总医院接受异基因外周血造血干细胞移植的244例患者(随访时间截止至2017年11月30日),总结异基因外周血造血干细胞移植后PTLD的发病率、危险因素、治疗疗效以及生存情况。结果:244例移植患者中,发生PTLD 22例,发病率为9.02%,其中病理确诊5例,临床诊断17例。22例PTLD患者均伴有EB病毒感染,均为使用ATG的亲缘单倍体相合造血干细胞移植或非亲缘供者造血干细胞移植患者。20例应用了利妥昔单克隆抗体单药或以利妥昔单克隆抗体为基础的联合治疗方案,17例有效,有效率85%。中位随访时间122 d,中位生存时间5(1-22)个月,总生存率50%。结论:异基因外周血造血干细胞移植后PTLD的发病与EB病毒感染关系密切。预处理方案中应用ATG是PTLD发病的高危因素。在无法取得病理诊断的情况下,应积极结合临床和实验室检查给予临床诊断。临床上越来越多地选用利妥昔单克隆抗体治疗PTLD。     

异基因造血干细胞移植后Epstein-Barr病毒相关性中枢神经系统移植后淋巴增殖性疾病诊治的研究进展

Epstein-Barr病毒(EBV)感染是异基因造血干细胞移植(allo-HSCT)后的常见并发症,因其可能导致致死性并发症——移植后淋巴增殖性疾病(PTLD)而倍受关注.利妥昔单抗的应用,可以改善PTLD的预后,但EBV相关性中枢神经系统(CNS)-PTLD较为罕见,且目前尚无公认的有效治疗方案,因此其预后较其他部位PTLD差.现就EBV相关性CNS广PTLD的诊治进展进行综述如下,旨在探讨对该病合适的治疗手段.     

血浆EB病毒DNA载量监测对单倍体造血干细胞移植后淋巴细胞增殖性疾病的预测价值北大核心CSCD

目的寻找可以协助诊断单倍体造血干细胞移植(haplo-HSCT)后淋巴细胞增殖性疾病(PTLD)的EB病毒DNA(EBV-DNA)载量及其持续时间的最佳临界值。方法回顾性分析北京大学血液病研究所2016年1月至12月期间haplo-HSCT后合并EBV感染患者的相关数据,通过构建ROC曲线计算约登指数寻找对PTLD有诊断意义的EBV-DNA载量及其持续时间的临界值。结果共纳入94例患者,其中20例(21.3%)发生PTLD,诊断PTLD时中位EBV-DNA载量为70400(1710~1370000)拷贝/ml,EBV血症中位持续时间为23.5(4~490)d。二元logistic回归分析显示,PTLD组与非PTLD组两组间EBV-DNA最高载量及EBV血症持续时间差异均有统计学意义(P=0.018,P=0.001)。构建ROC曲线计算约登指数,EBV-DNA载量≥41850拷贝/ml对PTLD有诊断意义[曲线下面积(AUC)=0.847],敏感度、特异度分别为0.611、0.932;EBV血症持续时间≥20.5 d对PTLD有诊断意义(AUC=0.833),敏感度、特异度分别为0.778、0.795。结论动态监测haplo-HSCT后PTLD高危患者的EBV载量及关注其持续时间有重要临床意义,有助于预测PTLD的发生并早期采取干预措施。     

儿童获得性再生障碍性贫血造血干细胞移植后淋巴组织增生性疾病的临床研究

目的 探讨儿童获得性再生障碍性贫血(AAA)异基因造血干细胞移植(allo-HSCT)后淋巴组织增生性疾病(PTLD)的流行病学、临床特点、诊治及预后.方法 选择2002年7月至2012年5月于本中心完成allo-HSCT的71例AAA患儿作为研究对象.患儿常规行氟达拉滨+环磷酰胺+兔-抗人T淋巴细胞球蛋白±全身放疗为基础的预处理,移植后主要采用环孢霉素和甲氨蝶呤预防移植物抗宿主病.对移植后外周血Epstein-Barr病毒(EBV)-DNA拷贝数持续升高的患儿,抢先予以利妥昔单抗治疗.确诊为PTLD后即予以免疫抑制剂减量或停药.结果 AAA患儿行allo-HSCT后PTLD的发生率为4.2％(3/71),临床均表现为抗感染治疗无效的反复发热伴扁桃体和淋巴结肿大.其中,2例患儿移植后予以监测外周血EBV-DNA拷贝数,在PTLD发生前均出现拷贝数的持续升高,且第1次予利妥昔单抗治疗后拷贝数仍持续上升.3例PTLD患儿中,2例治疗有效,随访至今仍无病生存;1例治疗效果不明显,于PTLD发生后34 d死亡.结论 PTLD是儿童AAA allo-HSCT后一种少见的并发症,病死率较高;动态监测患儿外周血EBV-DNA拷贝数对诊治有一定的指导作用;利妥昔单抗抢先治疗有利于降低PTLD的发生率及病死率.     

造血干细胞及器官移植后淋巴增殖性疾病2例

随着移植技术的不断开展和改进,越来越多的人从中受益,但其中一小部分患者在实体器官移植或同种异体骨髓移植后可出现一种B淋巴细胞的异常增殖,称为移植后淋巴增殖性疾病(post transplant lymphoproliferative disorders,PTLD)[1]。这种并发症发病率较低,但预后很差,一旦发生病     

造血干细胞移植后淋巴增殖性疾病

造血干细胞移植(HSCT)是血液系统恶性肿瘤以及某些遗传性或自身免疫性疾病的主要治疗手段之一。移植后淋巴增殖性疾病(PTLD)是一种少见但死亡率极高的HSCT后并发症。本文就近年来 HSCT后PTLD发病机制、特征和防治等方面的研究进展进行综述。     

Posttransplantation lymphoproliferative disease in children: otolaryngologic manifestations and management

BACKGROUND: Posttransplantation lymphoproliferative disease (PTLD) is associated with Epstein-Barr virus (EBV) infection after solid organ and bone marrow transplantation. METHODS: We did a retrospective analysis of cases with a diagnosis of PTLD at Children's Hospital of Wisconsin. RESULTS: Ten patients were identified. Seven of 10 cases (70%) were associated with bone marrow transplantation and 3 with solid organ transplantation. Three patients (30%) died of PTLD. The average time to development of PTLD after transplantation was 120 days. CONCLUSIONS: Otolaryngologic symptoms and findings are often the first manifestations of PTLD. Associated findings in this series included tonsillar necrosis, tonsillitis, airway obstruction, lymphadenitis, sinusitis, and otitis media. Diagnosis generally requires pathologic evaluation of tonsillar or adenoid tissue. Surgical intervention may also be important for relief of airway obstruction when present. Prompt recognition, diagnosis, and intervention with reduction in immunosuppression and antiviral therapy are essential to reduce the mortality of PTLD.     

利妥昔单克隆抗体在干细胞移植后淋巴细胞增殖性疾病中的应用

移植后淋巴细胞增殖性疾病（PTLD）是干细胞移植后的主要并发症之一,EB病毒感染是导致PTLD发生的常见原因之一。目前,针对PTLD的治疗措施有减少免疫抑制剂、局部治疗（放疗／手术切除）、抗病毒治疗、干扰素、化疗、抗CD20单克隆抗体（利妥昔单克隆抗体,商品名为美罗华）等,尤其随着美罗华的应用,使得胛LD的预后较前明显改善。本文主要就美罗华在细胞移植后淋巴细胞增殖性疾病中的应用做一综述,其中包括PTLD发生的危险因素,发病机制和美罗华的应用等。     

Infectious complications during immunochemotherapy of post-transplantation lymphoproliferative disease–can we decrease the risk? Two case reports and review of literature

BACKGROUNDPost-transplant lymphoproliferative disease (PTLD) is a heterogeneous group of diseases that develop after solid organ and hematopoietic stem cells transplantation related to intensive immunosuppression regimen, T-cell depletion and Epstein-Barr virus infection. Despite the improvement in the management of PTLD, the prognosis remains poor. Here we report the management of two transplanted patients with PTLD and infections during immunochemotherapy (ICTH).CASE SUMMARYOf 65-year-old woman 11 years after kidney transplantation (first case) presented with diffuse large B-cell lymphoma (DLBCL) CS III and started ICHT according to R-CHOP protocol. Despite the secondary prevention of neutropenic fever, the patient developed grade 4 neutropenia with urinary and pulmonary tract infections after the fifth cycle. ICTH was continued in reduced doses up to 7 cycles followed by involved-field radiation therapy of the residual disease. The second case presents a 49-year-old man, 8 years after liver transplantation due to cirrhosis in the course of chronic hepatitis B, who started ICTH for DLBCL Burkitt-like CS IV. The patient received four cycles of ICTH according to R-CODOX/R-IVAC protocol, with reduced doses. In both cases initially undertaken reduction of immunosuppression was ineffective to prevent infectious complications. Despite one incomplete ICHT treatment due to recurrent infections, both our patients remain in complete remission.CONCLUSIONReduction of immunosuppression and the doses of chemotherapeutics may be insufficient to prevent infectious complications during ICTH in PTLD patients.     

Epstein-Barr virus-associated post-transplant lymphoproliferative disease during dasatinib treatment occurred 10 years after umbilical cord blood transplantation

Post-transplant lymphoproliferative disease (PTLD) is defined as a lymphoma that occurs after solid-organ or hematopoietic stem-cell transplantation (HSCT), caused by immunosuppression and Epstein–Barr virus (EBV) reactivation. It is an important post-transplant complication that can be fatal. After HSCT, most PTLD occurs within 2 years. Recent evidence suggests that tyrosine kinase inhibitors (TKIs) are expected to be effective maintenance therapy after HSCT for Philadelphia chromosome-positive leukemia. However, it is unclear whether the use of TKIs might pose a risk of developing PTLD after HSCT. We present the first case of late-onset PTLD during dasatinib treatment, which occurred 10 years after umbilical cord blood transplantation (CBT). A 59-year-old man who received CBT for chronic myeloid leukemia blast phase needed long-term dasatinib therapy for molecular relapse. Ten years after CBT, he developed diffuse-large B-cell lymphoma (DLBCL). We observed chimerism of the DLBCL sample, which indicated complete donor type and EBV-DNA, and the patient was diagnosed with PTLD. Because of treatment resistance, he died 6 months after PTLD onset. Although he received no long-term administration of immunosuppressive agents, he received long-term dasatinib treatment, which suggests that prolonged dasatinib use after CBT caused EBV reactivation and led to PTLD. Our case suggests that the potential contribution of molecular-targeted agents after HSCT to the development of PTLD should be carefully considered.     

肾移植后尿瘘的诊断与治疗

背景:在目前肾源奇缺的情况下,因尿瘘而导致移植肾切除者尤为可惜,尿瘘的合理诊治应引起器官移植工作者的高度重视.目的:探讨肾移植后尿瘘的临床诊断与治疗措施.方法;对解放军南京军区福州总医院全军器官移植中心收治的16例肾移植后尿瘘病例资料进行回顾性分析.结果及结论:尿瘘发生率为1.26%,13例单纯性尿瘘行保守治疗,保守治疗成功11例.2例因输尿管远端坏死保守治疗失败,行移植肾输尿管膀胱再吻合及带蒂大网膜修补后治愈,尿瘘保守治疗成功率84.6%;3例复杂性尿瘘患者采用带蒂大网膜移植修补,均1次手术成功.结果提示,对于肾移植后尿瘘患者应高度重视和积极治疗,早期诊断,选择正确治疗措施是救治成功的关键,利用大网膜的生物学特性,采用带蒂大网膜修补肾移植后复杂性尿瘘和单纯性尿瘘保守治疗失败后病例具有取材方便、组织修复快、尿瘘复发率低的特点,适于临床推广应用.     

Mini-transplant for acute myeloblastic leukemia and myelodysplastic syndrome

The application of allogeneic hematopoietic stem cell transplantation (HSCT) has been limited to younger patients without organ dysfunctions due to transplant-related toxicities. Recently, non-myeloablative stem cell transplantation(NST) or reduced-intensity stem cell transplantation(RIST) has been developed as a less toxic HSCT, which enables the application of HSCT to patients of advanced age or with organ dysfunction by the use of mild conditioning regimen. The anti-leukemia effect mainly depends on the graft-versus-leukemia (GVL) effect. Several studies showed promising results of NST/RIST for acute myeloblastic leukemia(AML) and myelodysplastic syndrome(MDS). However, this novel treatment is still very toxic compared to conventional chemotherapy. We should continue clinical trials of NST/RIST to evaluate its efficacy and toxicity in patients with AML/MDS.     

流式细胞术检测异基因造血干细胞移植后多形性淋巴细胞增殖性疾病——附二例报告

目的 研究流式细胞术检测在异基因造血干细胞移植(allo-HSCT)后多形性淋巴细胞增殖性疾病诊断中的作用.方法 采用多色流式细胞术诊断allo-HSCT后多形性淋巴细胞增殖性疾病.结果 2例ailo-HSCT患者分别于移植后46 d(+46 d)和+50 d出现高热,多处淋巴结肿大,抗炎治疗无效,骨髓EB病毒DNA水平升高,经流式细胞术检测发现外周血多群轻链限制性单克隆B细胞和(或)浆细胞.诊断为移植后多形性淋巴细胞增殖性疾病.经免疫抑制减量、抗病毒、使用利妥昔单抗、输细胞毒性T淋巴细胞治疗后,经流式细胞术随访监测外周血和(或)骨髓标本.2例患者的B细胞克隆均消失,但是单克隆浆细胞持续存在或者新出现的克隆.1例患者2周后死亡;另1例患者仍在治疗中,外周血未见B细胞和浆细胞,骨髓未见B细胞,可见单克隆浆细胞.结论 使用流式细胞术可以有效诊断移植后多形性淋巴细胞增殖性疾病,并进行病情监测.随访过程中,骨髓标本可能比外周血标本敏感.allo-HSCT患者如果没有淋巴结活检,通过检测外周血也可以发现B细胞异常.     

中国“器官移植与脑死亡立法”的现状与挑战

目的通过比较世界发达国家器官移植立法和我国法律现状,探讨我国人体器官移植立法现状与面临的挑战。方法计算机检索WHO网站;美国NIH、美国移植学会（AST）、器官移植共享网（UNOS）、各国司法网站及相关会议论文和专家共识,纳人与器官移植与脑死亡立法相关的法律文本、文件、部门文件和专家共识,排除与器官移植与脑死亡技术相关的文献,将纳入文献按法律、法规、部门文件和专家共识分类分级,并根据不同主题结合我国情况作描述性对比分析。结果①纳入10个法律文本、1个法规、9个部门文件和4个专家共识。②国外器官移植立法20世纪60年代始于欧洲,英国最早,美国第三。而脑死亡立法于1978年由美国率先颁布。③1991年起,针对全球器官移植面临的全局性关键问题,世界卫生大会（WHA）等非政府组织先后颁布了7个共识文件,以规范业内人士行为。④中国（包括港、澳、台）至今尚未制定法律,均靠相关法规监管器官移植,比美、英立法落后40年和46年。结论中国器官移植和脑死亡立法上存在至少以下6种挑战：①死亡标准选择与器官供体来源。②对旅游名义的跨国界器官移植的监管和防范。③活体供者的风险评估及防范（保险方式）.④尸体器官捐献者的选择权——配偶、父母、子女的权限界定。⑤器官捐献的无偿或补偿原则。⑥脑死亡与器官移植法律单独还是合并立法。以上问题需要通过进一步研究来解决。     

Epstein-Barr virus-associated T-cell lymphoma in solid organ transplant recipients.

Post-transplantation lymphoproliferative diseases (PTLDs) are a heterogenous group of lymphoid proliferative disorders occurring in transplant patients. Most PTLDs are B-cell in origin; T-cell PTLDs are seldom reported, and EBV-associated T-cell PTLDs are rare. The first case of a T-cell, non-EBV-associated PTLD was first described in a renal allograft recipient in 1987. A total of 40 cases of T-cell PTLDs in solid organ transplant recipients have been reported. However, so far only 16 cases of EBV-associated T-cell PTLDs have been reported in the literature. The sites of occurrence of EBV-associated T-cell PTLDs were in the gastrointestinal tract, lungs, bone marrow, skin, liver and spleen. The pathogenesis of EBV-associated T-cell PTLD is uncertain; it is speculated that the EBV may infect a subset of T-cells that express the CD21 receptor. The present treatment of EBV-associated T-cell PTLD consists of surgical removal, reduction or withdrawal of immunosuppression and/or radiotherapy and chemotherapy. The prognosis is uncertain, and the 1-year survival for patients who were followed up for 1 year was 50%.