Progress on post transplant lymphoproliferative disorder

doi:10.3877/cma.j.issn.1674-3903.2021.05.011

Abstract

Abstract:

Post-transplant lymphoproliferative disorder (PTLD) is one of the most serious complications after solid organ transplantation (SOT). PTLD seriously affects the survival time of transplant recipients, the incidence of PTLD is related to Epstein-Barr virus (EBV) infection and suppression of immune function, and histopathology is the gold standard for its diagnosis. Current treatment options include dose-reduction of immunosuppressant, rituximab, EBV specific cytotoxic T lymphocyte infusion and chemotherapy, and so on, but the overall prognosis of PTLD patients is still poor. This review mainly summarizes the research progress of PTLD after SOT in recent years, in order to diagnose the occurrence of PTLD after SOT better, and provide theoretical and practical guidance for early intervention.

Key words: Post transplant lymphoproliferative disorder, Solid organ transplantation, Epstein-Barr virus

Ao Chen, Qiaoyan Lian, Jianheng Zhang, Xin Xu, Bing Wei, Yuhang Cai, Chunyan Wang, Huo Tan, Jianxing He, Chunrong Ju. Progress on post transplant lymphoproliferative disorder[J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(05): 307-312.

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References 47

1	Heslop HE. How I treat EBV lymphoproliferation[J]. Blood, 2009, 114(19): 4002-4008.
2	Martinez OM, Krams SM. The immune response to Epstein Barr virus and implications for posttransplant lymphoproliferative disorder[J]. Transplantation, 2017, 101(9): 2009-2016.
3	Abbas F, El Kossi M, Shaheen IS, et al. Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches[J]. World J Transplant, 2020, 10(2): 29-46.
4	Krams SM, Martinez OM. Epstein-Barr virus, rapamycin, and host immune responses[J]. Curr Opin Organ Transplant, 2008, 13(6): 563-568.
5	Vereide DT, Sugden B. Lymphomas differ in their dependence on Epstein-Barr virus[J]. Blood, 2011, 117(6): 1977-1985.
6	Burns DM, Tierney R, Shannon-Lowe C, et al. Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event[J]. Blood, 2015, 126(25): 2665-2675.
7	Ferreiro JF, Morscio J, Dierickx D, et al. EBV-positive and EBV-negative posttransplant diffuse large B cell lymphomas have distinct genomic and transcriptomic features[J]. Am J Transplant, 2016, 16(2): 414-425.
8	Courville EL, Yohe S, Chou D, et al. EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations[J]. Mod Pathol, 2016, 29(10): 1200-1211.
9	Dierickx D, Tousseyn T, Gheysens O. How I treat posttransplant lymphoproliferative disorders[J]. Blood, 2015, 126(20): 2274-2283.
10	Weisenburger DD, Gross TG. Post-transplant lymphoproliferative disorder: a heterogeneous conundrum[J]. Br J Haematol, 2017, 179(5): 854-856.
11	Doak PB, Montgomerie JZ, North JD, et al. Reticulum cell sarcoma after renal homotransplantation and azathioprine and prednisone therapy[J]．Br Med J, 1968, 4(5633): 746-748.
12	Opelz G, Döhler B. Lymphomas after solid organ transplantation: a collaborative transplant study report[J]. Am J Transplant, 2004, 4(2): 222-230.
13	Dierickx D, Tousseyn T, Sagaert X, et al. Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinicopathological characteristics and prognostic factors[J]. Leuk Lymphoma, 2013, 54(11): 2433-2440.
14	Zaffiri L, Long A, Neely ML, et al. Incidence and outcome of post-transplant lymphoproliferative disorders in lung transplant patients: Analysis of ISHLT Registry[J]. J Heart Lung Transplant, 2020, 39(10): 1089-1099.
15	Taylor AL, Marcus R, Bradley JA. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation[J]. Crit Rev Oncol Hematol, 2005, 56(1): 155-167.
16	Cherikh WS, Kauffman HM, Mcbride MA, et al. Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation[J]. Transplantation, 2003, 76(9): 1289-1293.
17	Opelz G, Daniel V, Naujokat C, et al. Epidemiology of pretransplant EBV and CMV serostatus in relation to posttransplant non-Hodgkin lymphoma[J]. Transplantation, 2009, 88(8): 962-967.
18	Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J]. Blood, 2016, 127(20): 2375-2390.
19	Sandlund JT, Guillerman RP, Perkins SL, et al. International pediatric non-hodgkin lymphoma response criteria[J]. J Clin Oncol, 2015, 33(18): 2106-2111.
20	Panagiotidis E, Quigley AM, Pencharz D, et al. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in diagnosis of post-transplant lymphoproliferative disorder[J]. Leuk Lymphoma, 2014, 55(3): 515-519.
21	Allen UD, Preiksaitis JK. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice[J]. Clin Transplant, 2019, 33(9): e13652.
22	Romero S, Montoro J, Guinot M, et al. Post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation[J]. Leuk Lymphoma, 2019, 60(1): 142-150.
23	刘占祥. 移植后淋巴细胞增殖性疾病诊断进展与治疗规范[J]. 白血病·淋巴瘤，2017, 26(8): 502-505.
24	Destefano CB, Desai SH, Shenoy AG, et al. Management of post-transplant lymphoproliferative disorders[J]. Br J Haematol, 2018, 182(3): 330-343.
25	San-Juan R, Manuel O, Hirsch HH, et al. Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey[J]. Clin Microbiol Infect, 2015, 21(6): 601-604.
26	Reshef R, Vardhanabhuti S, Luskin MR, et al. Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder (★) [J]. Am J Transplant, 2011, 11(2): 336-347.
27	Parker A, Bowles K, Bradley JA, et al. Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients-BCSH and BTS Guidelines[J]. Br J Haematol, 2010, 149(5): 693-705.
28	Dierickx D, Habermann TM. Post-transplantation lymphoproliferative disorders in adults[J]. N Engl J Med, 2018, 378(6): 549-562.
29	Doubrovina E, Oflaz-Sozmen B, Prockop SE, et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation[J]. Blood, 2012, 119(11): 2644-2656.
30	Heslop HE, Slobod KS, Pule MA, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients[J]. Blood, 2010, 115(5): 925-935.
31	Prockop SE, Vatsayan A. Epstein-Barr virus lymphoproliferative disease after solid organ transplantation[J]. Cytotherapy, 2017, 19(11): 1270-1283.
32	Haque T, Wilkie GM, Jones MM, et al. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial[J]. Blood, 2007, 110(4): 1123-1131.
33	Chiou FK, Beath SV, Wilkie GM, et al. Cytotoxic T-lymphocyte therapy for post-transplant lymphoproliferative disorder after solid organ transplantation in children[J]. Pediatr Transplant, 2018, 22(2): e13133.
34	Dharnidharka VR, Mohanakumar T. New approaches to treating B-cell cancers induced by Epstein-Barr virus[J]. N Engl J Med, 2015, 372(6): 569-571.
35	Choquet S, Leblond V, Herbrecht R, et al. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study[J]. Blood, 2006, 107(8): 3053-3057.
36	Choquet S, Oertel S, Leblond V, et al. Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ transplantation: proceed with caution[J]. Ann Hematol, 2007, 86(8): 599-607.
37	Choquet S, Trappe R, Leblond V, et al. CHOP-21 for the treatment of post-transplant lymphoproliferative disorders (PTLD) following solid organ transplantation[J]. Haematologica, 2007, 92(2): 273-274.
38	Trappe RU, Dierickx D, Zimmermann H, et al. Response to rituximab induction is a predictive marker in B-Cell post-transplant lymphoproliferative disorder and allows successful stratification into rituximab or R-CHOP consolidation in an international, prospective, multicenter phase Ⅱtrial[J]. J Clin Oncol, 2017, 35(5): 536-543.
39	Trappe R, Oertel S, Leblond V, et al. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial[J]. Lancet Oncol, 2012, 13(2): 196-206.
40	Odumade OA, Hogquist KA, Balfour HJ. Progress and problems in understanding and managing primary Epstein-Barr virus infections[J]. Clin Microbiol Rev, 2011, 24(1): 193-209.
41	Aldabbagh MA, Gitman MR, Kumar D, et al. The role of antiviral prophylaxis for the prevention of Epstein-Barr virus-associated posttransplant lymphoproliferative disease in solid organ transplant recipients: a systematic review[J]. Am J Transplant, 2017, 17(3): 770-781.
42	Perrine SP, Hermine O, Small T, et al. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies[J]. Blood, 2007, 109(6): 2571-2578.
43	Shyamasundar S, Dheen ST, Bay BH. Histone modifications as molecular targets in nasopharyngeal cancer[J]. Curr Med Chem, 2016, 23(2): 186-197.
44	Cavaliere R, Petroni G, Lopes MB, et al. Primary central nervous system post-transplantation lymphoproliferative disorder: an international primary central nervous system lymphoma collaborative group report[J]. Cancer, 2010, 116(4): 863-870.
45	Evens AM, Choquet S, Kroll-Desrosiers AR, et al. Primary CNS posttransplant lymphoproliferative disease (PTLD): an international report of 84 cases in the modern era[J]. Am J Transplant, 2013, 13(6): 1512-1522.
46	Wu M, Sun J, Zhang Y, et al. Intrathecal rituximab for EBV-associated post-transplant lymphoproliferative disorder with central nervous system involvement unresponsive to intravenous rituximab-based treatments: a prospective study[J]. Bone Marrow Transplant, 2016, 51(3): 456-458.
47	Läubli H, Tzankov A, Juskevicius D, et al. Lenalidomide monotherapy leads to a complete remission in refractory B-cell post-transplant lymphoproliferative disorder[J]. Leuk Lymphoma, 2016, 57(4): 945-948.

类型		淋巴结结构	形态学	EBV相关性	克隆性	治疗方案
早期病变		完整	浆细胞、免疫母细胞、小淋巴细胞	接近100%	多克隆	免疫抑制剂减量、利妥昔单抗及EBV-CTL输注
	鲜红滤泡增生
	反应性浆细胞增生
	传染性单核细胞增多样病变
多形性病变		破坏	B细胞成熟过程全谱系性变化	>90%	多克隆/单克隆	免疫抑制剂减量、利妥昔单抗及EBV-CTL输注
单形性病变		破坏	符合WHO非霍奇金淋巴瘤诊断标准	EBV(±)	单克隆	免疫抑制剂减量、利妥昔单抗及EBV-CTL输注
	B细胞肿瘤
	弥漫大B细胞淋巴瘤
	伯基特淋巴瘤
	T细胞/自然杀伤细胞肿瘤
	外周T细胞淋巴瘤-非特指型
	肝脾T细胞淋巴瘤
	其他类型
经典型霍奇金淋巴瘤		破坏	符合WHO经典型霍奇金淋巴瘤诊断标准	>90%	单克隆	霍奇金淋巴瘤化疗方案

类型		淋巴结结构	形态学	EBV相关性	克隆性	治疗方案
早期病变		完整	浆细胞、免疫母细胞、小淋巴细胞	接近100%	多克隆	免疫抑制剂减量、利妥昔单抗及EBV-CTL输注
	鲜红滤泡增生
	反应性浆细胞增生
	传染性单核细胞增多样病变
多形性病变		破坏	B细胞成熟过程全谱系性变化	>90%	多克隆/单克隆	免疫抑制剂减量、利妥昔单抗及EBV-CTL输注
单形性病变		破坏	符合WHO非霍奇金淋巴瘤诊断标准	EBV(±)	单克隆	免疫抑制剂减量、利妥昔单抗及EBV-CTL输注
	B细胞肿瘤
	弥漫大B细胞淋巴瘤
	伯基特淋巴瘤
	T细胞/自然杀伤细胞肿瘤
	外周T细胞淋巴瘤-非特指型
	肝脾T细胞淋巴瘤
	其他类型
经典型霍奇金淋巴瘤		破坏	符合WHO经典型霍奇金淋巴瘤诊断标准	>90%	单克隆	霍奇金淋巴瘤化疗方案

[1]	Mengyao Xiao, Xiaojuan Xin. Risk factors for adults with Epstein-Barr virus associated hemophagocytic lymphohistiocytosis [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(02): 73-81.
[2]	Weiyan Ling, Junqi Ding, Zhiao Tian, Jianhua. Yao. Clinical characteristics and peripheral blood lymphocytes immunophenotype of 48 adult patients with chronic active Epstein-Barr virus infection [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2020, 14(05): 424-428.
[3]	Chengjuan Xie, Mangui Li, Qixia Ren, Ning Tang, Chenghua Liu, Shengmei Li, Huiying Ma. Coagulation and immunological indexes in children with Epstein-Barr virus infection and its clinical significance [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2019, 13(02): 162-166.
[4]	Ting Pan, Peipei Zhou, Xuebing Yan. Clinical analysis on 162 cases with Epstein-Barr virus infection [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(04): 348-353.
[5]	Organ Transplantation and Rehabilitation Committee of Chinese Medical Association of Rehabilitation. Expert consensus on diabetes mellitus after solid organ transplantation in adults [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(04): 205-220.
[6]	Qi Chen, Jiayu Guo, Zhongbao Chen, Xiaoxiong Ma, Tianyu Wang, Jilin Zou, Long Zhang, Zhitao Cai, Tao Qiu, Jiangqiao Zhou. Combined heart and kidney transplantation: a report of 3 cases [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(02): 124-127.
[7]	Chinese College of Transplant Doctors, Chinese Medical Doctor Association;, Chinese Society of Organ Transplantation, Chinese Medical Association. Chinese experts consensus on the management of surgical site infection in solid organ transplantation (2022 edition) [J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(03): 129-139.
[8]	Liang Ai, Ke Cheng, Sheng Zhang. Post transplant lymphoproliferative disorder with tuberculosis after secondary renal transplantation: a case report [J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(01): 46-48.
[9]	Zhengbin Hu, Xin Zhou, Yan Xiong, Xiaoli Fan, Zhipeng Fan, Qifa Ye. Research progress on biomarkers related to long-term graft survival evaluation after solid organ transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(04): 244-249.
[10]	Ziyan Yan, Fangxiang Fu, Yun Miao. Research progress on cryptococcosis after solid organ transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2020, 14(04): 263-267.
[11]	Dongyue Liu, Man Xie, Xinjuan Kong, Wei Rao. The epidemiology and influence factors of lower digestive tract diseases in solid organ transplantation recipients [J]. Chinese Journal of Transplantation(Electronic Edition), 2019, 13(01): 71-74.
[12]	Manpin Zhang, Xia Qin, Chengjuan Luo, Jianmin Wang, Changying Luo, Jing Chen. Risk factors and prognosis of Epstein-Barr virus DNAemia in children with aplastic anemia after allogeneic hematopoietic stem cell transplantation [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(02): 90-96.
[13]	Yanlin Jia, Yanqin Hao. Epstein-Barr virus infection: mechanism and clinical research [J]. Chinese Journal of Clinicians(Electronic Edition), 2019, 13(08): 624-626.
[14]	Yang Zhang, Fang Deng, Shaohua Chen, Zhaowu Chen, Chunyang Dai, Ming Li. Preliminary study on the change of Epstein-Barr virus DNA load in patients with nasopharyngeal carcinoma [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2019, 07(01): 22-25.
[15]	Shuo Meng, Zhao Wang. The mechanism of Epstein-Barr virus infection [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2019, 07(01): 2-4.

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