异基因造血干细胞移植后淋巴组织增殖性疾病一例并文献复习

目的 探讨造血干细胞移植术后淋巴组织增殖性疾病(PTLD)的诊断和治疗.方法 回顾性分析1例异基因造血干细胞移植后PTLD的临床表现、诊断和治疗过程,并复习相关文献.结果 2007年1月至2012年11月196例造血干细胞移植后受者中有1例发生PTLD,发生率为0.5％.该例受者的临床表现不典型,主要表现为反复发热、多处淋巴结肿大和肺部多发性结节病变等,淋巴结活检提示弥漫大B细胞淋巴瘤.停用免疫抑制剂2个月后体温恢复正常,肿大的淋巴结和肺部结节病变完全消失.结论 PTLD是造血干细胞移植术后严重的并发症之一,具有独特的形态和临床特征.病因可能与EB病毒感染和免疫抑制有关,需经病理组织学检查确诊.治疗方法多样,减少免疫抑制剂用量可能是一种有效治疗措施.     

儿童肝移植术后淋巴组织增殖性疾病11例临床分析

目的探讨儿童肝移植术后淋巴组织增殖性疾病(posttransplant lymphoproliferative disorder, PTLD)的临床表现、病理特征、治疗方案及预后。方法对2016年10月至2021年10月复旦大学附属儿科医院收治的11例儿童肝移植术后PTLD的临床资料进行回顾性分析。其中, 男5例, 女6例;年龄1～8岁。行亲属活体肝移植术9例, 接受死亡器官捐献供肝移植术2例, 术后均采用他克莫司联合甲泼尼龙的免疫抑制方案。11例患儿临床表现主要包括:淋巴结肿大, 脾大, 贫血, 发热, 消化系统症状(腹泻、腹痛、腹水、便血、肠套叠等);实验室检查方面主要表现为低蛋白血症和转氨酶升高, 11例患儿血液EB病毒DNA(EBV-DNA)均阳性;9例患儿行PET-CT检查考虑PTLD;10例患儿根据病理检查结果明确诊断, 其中淋巴组织增生3例, 浆细胞增生性PTLD 1例, 多形性PTLD 2例, 弥漫性大B细胞淋巴瘤2例, 传染性单核细胞增生性PTLD 1例, Burkitt淋巴瘤1例。结果 11例儿童受者确诊PTLD后, 均减量或停用他克莫司, 11例患儿均接受利妥昔单...     

肝移植后移植物抗宿主病的诊断和治疗

目的 探讨肝移植后发生移植物抗宿主病(GVHD)的诊断和治疗方法.方法 回顾性分析2002年4月至2006年3月间8例肝移植后发生GVHD受者的临床资料,通过观察这8例受者的临床症状与体征,以及分析肝功能、血常规、骨髓细胞学、细菌培养、病毒检测和皮肤病理学等检查结果,总结诊断与治疗经验.结果 肝移植受者发生GVHD的临床表现为:术后1～4周出现发热、全身皮疹、全血细胞减少、腹泻和腹痛等,但肝功能正常.皮肤组织病理学表现为:表皮角化不良、松解,棘层细胞水肿,基底层液化变性,真皮浅层淋巴细胞浸润.8例受者经减少免疫抑制剂的用量、有效控制非特异性炎症反应、改善造血功能、防治感染和加强营养支持等治疗后,其中7例康复出院,并长期健康存活;仅1例治疗无效死亡.结论 肝移植后GVHD的诊断主要依据典型的临床表现和特异性的皮肤组织病理学改变.诊断明确后应最大程度的减少免疫抑制剂的用量,有效控制GVHD引起的急性炎症反应,促进造血功能恢复.     

儿童肝移植术后淋巴组织增殖性疾病的临床及病理特点——单中心回顾性分析

目的分析儿童肝移植术后淋巴组织增殖性疾病(post-transplant lymphoproliferative disorder,PTLD)的临床及病理特点,为诊断及治疗提供参考依据。方法收集2020年5月至2022年5月天津市第一中心医院儿童肝移植科收治的肝移植术后PTLD患者的临床及病理资料。包括性别、年龄、手术方式、术后免疫抑制方案、PTLD治疗方案、预后、临床表现、肝功能、血浆EBV-DNA、影像学检查结果,依据2016年WHO淋巴组织肿瘤分类进行病理学分型及免疫组化染色结果。回顾性分析患者的临床、病理及预后的特点。结果肝移植术后经病理学确诊的PTLD患者8例,其中男性4例,女性4例,年龄为1~4岁。8例患者原发病均为胆道闭锁且均行亲属活体肝移植术。本组病例中,5例出现淋巴结肿大,5例出现消化系统症状(包括腹痛、肠梗阻、腹水、腹胀),4例出现肝功能异常,3例出现发热,1例出现肝、肾功能异常。血浆EBV-DNA平均为46072 copies/ml。本组病例中非破坏性、多形性和单形性分别占12.5%(1/8)、25%(2/8)和62.5%(5/8)。5例单形性PTLD中伯基特(Burkitt)淋巴瘤、弥漫性大B细胞淋巴瘤和成熟T细胞淋巴瘤,分别占60%(3/5)、20%(1/5)和20%(1/8)。患者确诊后均减量或停用他克莫司并联合利妥昔单抗治疗,其中6例接受化疗,2例接受血液透析治疗,2例行局部占位手术切除治疗。8例患者中7例病情缓解,1例死亡。结论PTLD的早期诊断、根据病理分型选择合理的治疗方案有助于提高患者预后,接受化疗的患儿应警惕肿瘤溶解综合征并及时给予积极有效干预。     

肾移植术后淋巴增殖性疾病的诊治体会

目的探讨肾移植术后淋巴细胞增殖性疾病(PTLD)的发病原因、临床特点、诊治方法及预后。方法回顾性分析2000年1月至2019年1月海军军医大学长征医院2844例肾移植受者中术后并发PTLD的13例受者的临床资料,收集受者性别、年龄、血肌酐、药物浓度、糖尿病、肾移植术后有无移植肾功能延迟恢复、急性排斥反应和免疫抑制剂方案的使用等相关资料。13例PTLD受者中,男11例,女2例,确诊时年龄为55岁(31~78岁)。结果PTLD病变位置分布在肺部1例,胃肠道8例,区域淋巴结2例,皮肤1例,颅内1例,均病理诊断为弥漫性大B淋巴细胞淋巴瘤,距肾移植手术中位时间为86个月(12~204个月)。76.9%受者病理组织EB病毒检测呈阳性。确诊后给予免疫抑制剂减量为主的综合治疗,无法耐受利妥昔单抗+CHOP(R-CHOP)方案化学药物治疗的受者切换为利妥昔单抗+来那度胺(R2)方案,2例受者肺部感染死亡,完全缓解10例,部分缓解1例,病情进展1例,总有效率91.6%。结论肾移植术后淋巴细胞增殖性疾病进展迅速,病死率高,与EB病毒感染密切相关,减少免疫抑制剂用量是综合治疗的核心,根据受者耐受性选择合理的化学药物治疗方案,R2方案为无法耐受一线R-CHOP方案的受者更多选择。     

肝移植术后免疫抑制剂撤退的研究进展

肝移植是治疗终末期肝病的最有效手段,患者术后1年和5年生存率已分别达到85%和70%[1-2].在实体器官移植中肝脏属于免疫特惠器官,但为了预防术后出现排斥反应,移植患者术后仍需长期使用免疫抑制剂.这不仅加重患者的经济负担,还会导致移植术后患者出现血清肌酐升高、高血压、高血脂和高血糖等,引起肾功能损害、心脑血管疾病、机会性感染和移植术后淋巴组织增生性疾病（post-transplant lymphoproliferative disorder,PTLD）,严重影响患者的生活质量和长期存活.因此,如何在逐渐减少免疫抑制剂用量的基础上,完全停用免疫抑制剂是临床肝移植术后免疫调节的终极目标.     

肾移植后淋巴组织增生性疾病的临床和病理学特点

目的 探讨肾移植术后发生淋巴组织增生性疾病(PTLD)的临床及病理学特点.方法 回顾性分析3例肾移植术后PTLD患者的临床和病理学特点,并对与PTLD相关的文献进行复习.结果 3例患者肾移植后使用的基础免疫抑制剂为环孢素A或他克莫司,从接受移植到诊断PTLD的时间分别为10年、4年及2个月.病理组织学类型:2例为单形性B淋巴细胞型PTLD,1例为浆细胞增生样PTLD.确诊后的治疗包括免疫抑制剂减量及放疗和化疗.2例单形性PTLD经治疗后,患者均在1年内死亡.1例浆细胞增生样PTLD患者经治疗后,无瘤存活已42个月.结论 PTLD是发生在器官移植后具有独特形态和临床特征的淋巴组织增生异常;治疗上以免疫抑制剂减量及放疗和化疗为主;单形性PTLD预后甚差.     

肝移植术后肝脏局部淋巴增生性疾病(附3例报告)

目的总结并探讨肝移植术后肝脏局部淋巴增生性疾病（LL-PTLD）的临床、病理特点及防治措施。方法回顾性研究2003年至2006年间收治的3例LL-PTLD的临床和病理学资料，对供、受者病理标本的组织与分子病理学检查结果（包括CD20、CD45RO、LMP-I）分析。结果例1为T细胞性淋巴瘤，检查证实淋巴瘤细胞来源于供者；检查EB病毒（EBV）-LMP阳性；2次肝移植术后6个月因淋巴瘤复发死亡。例2为B细胞性淋巴瘤，淋巴瘤细胞来源于供者；检查EBV-LMP阳性；2次肝移植术后死于肺部感染。例3为浆细胞性淋巴瘤；检查EBV-LMP阳性；术后给予相应治疗，随访11个月，仍无瘤存活。结论肝移植术前应常规进行供、受者EBV感染的相关检查，对肝移植术后PTLD的高危患者，术后应使用低剂量的免疫抑制剂，常规应用抗病毒药物；对于出现无法解释的肝门部梗阻的患者，应高度怀疑LL-PTLD的存在，并考虑针吸活检，尽早确诊和治疗。     

肝移植术后急性移植物抗宿主疾病的诊断和治疗(附2例报道)

目的 探讨肝移植术后早期并发急性移植物抗宿主疾病(GVHD)的诊断和治疗.方法 回顾性分析我院2006年5月至2007年10月期间行肝移植手术50例,其中2例术后并发GVHD,分析该2例肝移植术后第14 d和第18 d以出现不明原因发热、皮疹、口腔多发溃疡、全血细胞减少、皮肤病理活检等临床资料为诊断依据和以不同的免疫抑制剂治疗的方案.结果 第1例患者加强免疫抑制剂治疗,发生败血症于术后67 d死于多器官功能衰竭;第2例减少免疫抑制剂治疗,术后96 d治愈.结论 肝移植术后并发GVHD,减少免疫抑制剂方案可能是一种有效方案,但应警惕急性排斥反应和继发感染发生.     

肝移植术后间质性肺炎的诊治经验

目的总结诊治肝移植患者术后间质性肺炎的经验。方法回顾分析2001年4月至2009年6月期间诊治的8例同种异体肝移植术后间质性肺炎病人的临床资料。结果8例肝移植术后间质性肺炎患者的发病时间为术后17～117 d,平均84 d,其中7例发生于术后2～4个月。8例均有发热,其中抗巨细胞病毒(CMV)特异性抗体CMV-IgM阳性及CMV-DNA阳性4例,胸部CT均有明显间质性肺炎表现。经调整抗排斥药物用量、使用更昔洛韦及呼吸支持治疗后,4例患者临床症状明显好转,胸部CT恢复正常;4例患者病情进展,继发细菌或真菌感染,死于呼吸衰竭。结论肝移植后间质性肺炎临床表现无特异性,病死率高,应及时予胸部CT检查,同时加强病原体的监测。确诊后予调整免疫抑制剂用量、早期抗病毒治疗及对症支持治疗,以提高治愈率。     

Graft outcomes following diagnosis of post‐transplant lymphoproliferative disease in pediatric kidney recipients: a retrospective study

Data related to graft outcomes following post‐transplant lymphoproliferative disease (PTLD) in pediatric kidney transplantation are scarce. Data were analyzed retrospectively from 12 children (eight boys) for 3 years after diagnosis of PTLD, with a loss of follow‐up after 2 years in two of 12. In all cases, intensity of immunosuppressive therapy was reduced, which switched from calcineurin inhibitor to a mammalian target of rapamycin (mTOR) inhibitor in ten cases. Nine children were treated with six doses of rituximab according to the PED‐PTLD‐2005 protocol, with additional treatment in one child as per protocol. One patient received EuroNet‐PHL C1. In four patients, donor‐specific antibodies were detected after PTLD diagnosis at 3, 4, 5 and 7 years, respectively. One patient developed chronic antibody‐mediated rejection (cAMR) 12 years after diagnosis, losing the graft 1 year later. Three patients with recurrence of the original disease also lost their grafts, one at the time of diagnosis of PTLD, and two after 4 years. Range‐based analysis of variance showed that there was no decrease in estimated GFR at 1, 2, or 3 years after diagnosis of PTLD (P = 0.978). In conclusion, treatment of PTLD with reduced immunosuppression is safe and efficient. This may be due to B‐cell‐depleting therapy of PTLD with rituximab.     

Clinical usefulness of FDG-PET/CT scan imaging in the management of posttransplant lymphoproliferative disease

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is, aside skin cancer, the most common malignancy occurring after solid organ transplant in adults. Fluorodeoxyglucose (FDG) positron emission tomography (PET) has proved useful in the management of lymphomas. METHODS: We report our experience with the use of FDG-PET inline with computed tomography (CT) scanning in the management of four transplant recipients with histologically confirmed PTLD, including three monomorphic PTLDs and one polymorphic PTLD. RESULTS: FDG-PET/CT scan at diagnosis showed increased FDG uptake in all examined PTLD lesions, and the disease was upstaged on the basis of FDG-PET/CT scan results over conventional CT scanning in one patient. At the end of treatment, PET/CT scans no longer demonstrated FDG uptake in the original PTLD lesions in all patients. Complete remission of disease persisted for at least 1 year after diagnosis in all. CONCLUSIONS: Our results strongly support that FDG-PET scanning is highly specific for diagnosis and follow-up of PTLD. The clinical relevance of including FDG-PET/CT scanning in the management of PTLD should be evaluated in a larger prospective cohort study.     

Use of mycophenolate mofetil as rescue therapy after pediatric liver transplantation

BACKGROUND: Mycophenolate mofetil (MMF) has been increasingly used after liver transplantation (LT) in adults. We report our preliminary experience with MMF as rescue therapy after pediatric LT. METHODS: A total of 19 children received MMF for 21 indications. Median age at LT was 30 months (range 7-149). The median initial oral dose of MMF was 23 mg/kg/day (range 12-43) orally. Median follow-up after initiation of MMF therapy was 642 days (range 229-1606). RESULTS: 1) Efficacy: MMF was indicated for rejection or insufficient immunosuppression in 16 cases, with normalization of both liver function tests and liver histology in 10 (62%). MMF was successfully used in one patient with post-LT immmune hepatitis and one patient with corticodependence. In three patients with renal function impairment, MMF allowed reduction of cyclosporine A or tacrolimus blood levels, without subsequent rejection. 2) Tolerance: Six patients (32%) experienced eight side effects, mainly gastrointestinal and hematological, which resolved after cessation of MMF in five cases and dose reduction in three. One case of posttransplant lymphoproliferative disease (PTLD) occurred under MMF therapy (5.2%). Four patients had EBV primary infection, while under MMF therapy, without subsequent PTLD. Three patients had CMV primary infection, and five CMV reactivation, under MMF therapy. Seven remained asymptomatic, and one presented with CMV enteritis. CONCLUSIONS: These preliminary results suggest that MMF is an effective and safe immunosuppressant in pediatric LT recipients. Its use is hampered by frequent gastrointestinal and hematological side-effects. MMF does not seem to increase the risk of PTLD nor CMV disease.     

Posttransplant lymphoproliferative disorders in transplant recipients

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% and 32%. The incidence of PTLD mainly depends on the transplanted organ, the immunosuppressive drugs, the viral serology, and the age of the recipient. The aim of our study was to analyze our patients diagnosed with PTLD. Among 1040 transplantations, including 931 renal, 14 heart, 55 liver and 40 allogeneic peripheral blood stem cell (PBSC), 8 patients (7 male, 1 female) were diagnosed with PTLD. Five patients had undergone renal, one cardiac, one liver, and one PBSC transplantations. Four patients were diagnosed within the first year of transplantation. Six patients presented with abdominal disease, one with convulsions, and one with peripheral lymph node involvement. According to the World Health Organization classification system, six patients were diagnosed as diffuse large B-cell lymphoma, one patient Burkitt's lymphoma, and one polymorphic PTLD. At the time of diagnosis, 7 patients showed positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) Ig G and negative Ig M; one patient, positive EBV Ig M and negative CMV Ig G and M. EBV viral load was extremely high in the plasma of two patients by polymerase chain reaction. One of these patient's pathologic tissue revealed positive EBV DNA, which was not detected in six of the other eight patients. This patient was an 8-year-old boy diagnosed with Burkitt's lymphoma at 31 months after liver transplantation. Seven patients died of disease or complications of chemotherapy. Only one patient survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate was high among our patients with PTLD. To decrease the incidence of PTLD and related mortality, risk factors must be evaluated in multicenter studies.     

Use of Serum Protein Electrophoresis to Monitor Patients with Post-transplant Lymphoproliferative Disorder

Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation. Reduction in immunosuppression is usually the first line of therapy and is often curative. While undergoing treatment, imaging studies including MRI and CT scans are commonly used to follow the disease course. Laboratory studies such as lactate dehydrogenase and Epstein-Barr virus PCR can also be used to monitoring disease status. We report here a case of PTLD developing 48 months post renal transplant. A monoclonal protein (M protein) was demonstrated at diagnosis with a corresponding antibody expressed on the malignant lymphocytes. The patient was followed with serial serum protein electrophoreses (SPEP) to monitor his response to therapy. The amount of M protein paralleled the disease course, decreasing as the clinical symptoms improved. This case illustrates the utility of using SPEP to monitor patients with PTLD.     

EBV-associated recurrent Hodgkin''s disease after renal transplantation

Hodgkin's disease is recognized as part of the spectrum of post-transplantation lymphoproliferative disorders (PTLD), although it is still an uncommon de novo malignancy in this population. Epstein-Barr virus (EBV) has been linked to both post-transplant non-Hodgkin's lymphomas and Hodgkin's disease. We report a case of recurrent Hodgkin's disease in a patient who received a renal transplant in childhood and later developed EBV-associated Hodgkin's disease with remission after chemotherapy until subsequent relapse 9 years later that was successfully treated. To our knowledge, this is the first report of recurrent Hodgkin's disease in a transplant recipient. We briefly discuss the pathogenesis of and risk factors for EBV-related PTLD, utility of EBV load surveillance, and the options for treatment of PTLD including immunosuppression reduction, antiviral therapy, anti-CD20 monoclonal antibodies, cytotoxic T cells, and the possible roles of interferon-alpha and rapamycin.     

Posttransplant lymphoproliferative disorders of the central nervous system after kidney transplantation: single center experience over 40 years. Two case reports

Posttransplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications of organ transplantation. PTLD sometimes involves the central nervous system (CNS), but the clinical characteristics are not well recognized. A total of 631 patients received kidney transplantation at Osaka University Hospital between March 1965 and December 2008. Two of the 631 patients (0.32%) developed CNS PTLD. A 40-year-old Japanese woman suffered onset of CNS PTLD 5 years after renal transplantation. After diagnosis based on histological examination by open biopsy, she obtained remission with dose increase of steroid and dose reduction of mycophenolate mofetil. She experienced relapse 20 months after first remission. She underwent second biopsy and the diagnosis was recurrent CNS PTLD. Further reduction of mycophenolate mofetil and increase of steroid led to second remission. The disease remained in complete remission at 60 months after first onset. A 61-year-old woman suffered onset of CNS PTLD 19 years after renal transplantation. After tumor removal, whole brain irradiation was performed. The disease remained in remission at 54 months after onset. Histological examination showed polymorphic-type PTLD in both cases. The first case of polymorphic CNS PTLD was successfully treated by modulation of immunosuppressants without radiation therapy even at recurrence. PTLD should be included in the differential diagnosis of brain tumors in recipients of solid organ transplantation, and histological subtype should be carefully identified to establish the correct treatment strategy.     

肝移植术后移植物抗宿主病(附1例报告)

目的:探讨与总结肝移植术后移植物抗宿主病(graft versus host disease,GVHD)的诊断及治疗经验。方法:分析1例男性53岁病人,因肝癌行原位肝移植,术后1个月发生GVHD的临床经过和实验室检查结果。临床表现和皮肤活检为其诊断依据。结果:病人在术后出现不明原因的发热、皮疹、腹泻、全血细胞减少,经减少免疫抑制剂,加用激素冲击等治疗后,术后3个月病人治愈。结论:肝移植术后GVHD早期易被误诊,治疗效果不佳,但可以临床治愈。