陆军军医大学第二附属医院血液病医学中心,重庆 400037
Received:22 April 2024,
Revised:2024-05-07,
Accepted:22 May 2024,
Published:28 July 2024
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王聪聪,朱丽丹,刘嘉,等.移植后淋巴增殖性疾病患者的临床分析[J].重庆医科大学学报,2024,49(7):813-819.
Wang Congcong,Zhu Lidan,Liu Jia,et al.Clinical analysis of patients with post-transplant lymphoproliferative disease[J].Journal of Chongqing Medical University,2024,49(7):813-819.
王聪聪,朱丽丹,刘嘉,等.移植后淋巴增殖性疾病患者的临床分析[J].重庆医科大学学报,2024,49(7):813-819. DOI: 10.13406/j.cnki.cyxb.003535.
Wang Congcong,Zhu Lidan,Liu Jia,et al.Clinical analysis of patients with post-transplant lymphoproliferative disease[J].Journal of Chongqing Medical University,2024,49(7):813-819. DOI: 10.13406/j.cnki.cyxb.003535.
目的
2
分析移植后淋巴增殖性疾病(post-transplant lympho-proliferative disease,PTLD)的临床特点,探讨该病发生的危险因素。
方法
2
选取陆军军医大学第二附属医院2017年1月至2023年12月病理诊断为PTLD的患者10例为研究组。分析10例PTLD患者的移植预处理方案、抗胸腺细胞球蛋白(anti-themocyte globulin,ATG)使用情况、供/受者EB病毒(Epstein-Barr virus,EBV)感染情况等因素对PTLD发生及转归的影响。按照1∶4比例个体匹配,选取同时期同一移植中心40例造血干细胞移植(hematopoietic stem cell transplantation,HSCT)患者为对照组,比较2组一般情况及检查检验指标,对PTLD的相关风险因素进行logistic回归分析。
结果
2
本研究10例PTLD患者主要表现为发热及淋巴结肿大:颈部4例,腹股沟、耳后、腹腔各1例;回肠、肺脏、肝脏淋巴组织增生各1例。病理类型以单形性变为主,共8例,多形性变2例。B细胞来源9例,以高增殖活性B细胞淋巴瘤为主,可疑T细胞来源1例。logis
tic回归分析显示免疫抑制剂使用时间和供者EB病毒水平与PTLD发生相关:PTLD组免疫抑制剂使用时间低于对照组[131.50(61.00,197.75) d vs. 244.50(142.00,424.00) d,
Z
=2.547,
P
<
0.05],PTLD组供者EBV DNA阳性比例显著高于对照组(75.0% vs. 17.4%,
χ
2
=5.888,
P
<
0.05);患者年龄、疾病诊断、移植预处理方案、供受者关系、供受者血型、人类白细胞抗原(human leukocyte antigen,HLA)相合程度、移植物抗宿主病(graft versus host disease,GVHD)预防方案、ATG使用情况、巨细胞病毒(cytomegalovirus,CMV)/BK病毒(BK virus,BKV)/JC病毒(JC virus,JCV)水平、移植前后EB病毒水平、GVHD与PTLD发生无明显相关性(
P
>
0.05)。发生PTLD后,R-CHOP(利妥昔单抗+环磷酰胺+多柔比星+长春新碱+泼尼松龙)治疗组生存时间长于未治疗和非R-CHOP治疗组[(345.13±110.84) d vs. (9.00±7.51) d/21.00 d,
P
<
0.05]。
结论
2
供者EB病毒DNA水平和免疫抑制剂使用时间与PTLD发生呈现相关性,提示移植前需监测供者EB病毒水平,阳性供者应给予相应治疗;移植后发生PTLD患者首先会减停免疫抑制剂,所以会造成免疫抑制剂使用时间长是PTLD发生保护性因素的假象。发生PTLD后,及时进行R-CHOP方案治疗能明显改善患者预后及生存时间。
Objective
2
To analyze the clinical characteristics of post-transplant lymphoproliferative disease(PTLD) and explore the risk factors for its occurrence.
Methods
2
Ten patients with pathologically diagnosed PTLD at the Second Affiliated Hospital of Army Medical University between January 2017 and December 2023 were selected as the study group. The effects of transplant preconditioning protocol,anti-thymocyte globulin(ATG) usage,and Epstein-Barr virus(EBV) infection in donors/recipients on the occurrence and outcome of PTLD were analyzed. Using a 1∶4 individual matching ratio,40 patients with hematopoietic stem cell transplantation (HSCT) during the same period at the same transplantation center were selected as the control group. General information and laboratory indicators were compared between the two groups. Logistic regression analysis was conducted on the risk factors of PTLD.
Results
2
The main manifestations of 10 PTLD patients in this study were fever and lymphadenectasis,including 4 cases in cervical lymph nodes,1 case in ingu
inal lymph nodes,1 case in retroauricular lymph nodes,and 1 case in celiac lymph nodes. In addition,there was 1 case each of lymphoid hyperplasia in the ileum,lung,and liver. The pathological types were mainly monomorphic changes(8 cases),followed by polymorphic changes(2 cases). Nine cases were derived from B cells,mainly high-proliferative activity B-cell lymphoma,and 1 case was suspected to be derived from T cells. Logistic regression analysis showed that the number of days of immunosuppressant use and the level of EBV in donors were associated with the occurrence of PTLD. The median number of days of immunosuppressant use was significantly lower in the PTLD group than in the control group [131.50(61.00,197.75) d vs. 244.50(142.00,424.00) d,
Z
=2.547,
P
<
0.05
]
. The proportion of EBV DNA-positive donors was significantly higher in the PTLD group than in the control group(75.0% vs. 17.4%,
χ
2
=5.888,
P
<
0.05). The occurrence of PTLD was not significantly correlated with patient age,disease diagnosis,transplant preconditioning protocol,donor-recipient relationship,donor-recipient blood type,human leukocyte antigen(HLA) matching degree,graft versus host disease(GVHD) prevention plan,ATG usage,CMV/BK/JC virus levels,EBV levels before and after transplantation,and GVHD(
P
>
0.05). After the occurrence of PTLD,the survival time of patients in the R-CHOP(rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone) treatment group was significantly higher than that in the untreated and non-R-CHOP treatment groups [(345.13±110.84) d vs. (9.00±7.51) d/21.00 d,
P
<
0.05
]
.
Conclusion
2
The level of EBV DNA in donors and the duration of immunosuppressant use are associated with the occurrence of PTLD,suggesting that the level of EBV in donors should be monitored before transplantation,and positive donors should be given corresponding treatment. After the occurrence of PTLD,patients usually have immunosuppressants reduced or discontinued,which creates the misconception that prolonged use of immunosuppressant is a protective factor for the occurrence of PTLD. Timely R-CHOP treatment can significantly improve the prognosis and survival time of patients with PTLD.
陈 奥 , 练巧燕 , 张建恒 , 等 . 移植后淋巴增殖性疾病研究进展 [J ] . 中华移植杂志 (电子版), 2021 , 15 ( 5 ): 307 - 312 .
Chen A , Lian QY , Zhang JH , et al . Progress on post transplant lymphoproliferative disorder [J ] . Chin J Transplant Electron Ed , 2021 , 15 ( 5 ): 307 - 312 .
陈 静 , 桑 蝶 . 移植后淋巴细胞增殖性疾病的研究现状及进展 [J ] . 中国临床医生杂志 , 2023 , 51 ( 8 ): 898 - 902 .
Chen J , Sang D . Research status and progress of lymphoproliferative diseases after transplantation [J ] . Chin J Clin , 2023 , 51 ( 8 ): 898 - 902 .
中华医学会血液学分会 , 中国医师协会血液科医师分会 . 造血干细胞移植后EB病毒相关淋巴增殖性疾病中国专家共识(2022年版) [J ] . 中华血液学杂志 , 2022 , 43 ( 9 ): 716 - 725 .
Chinese consensus on the diagnosis and management of Epstein-Barr virus-related post-transplant lymphoproliferative disorders after hematopoietic stem cell transplantation ( 2022 )[J ] . Chin J Hematol, 2022 , 43 ( 9 ): 716 - 725 .
Pegoraro F , Favre C . Post-transplantation lymphoproliferative disorder after haematopoietic stem cell transplantation [J ] . Ann Hematol , 2021 , 100 ( 4 ): 865 - 878 .
Aguilera N , Gru AA . Reexamining post-transplant lymphoproliferative disorders:newly recognized and enigmatic types [J ] . Semin Diagn Pathol , 2018 , 35 ( 4 ): 236 - 246 .
Amengual JE , Pro B . How I treat posttransplant lymphoproliferative disorder [J ] . Blood , 2023 , 142 ( 17 ): 1426 - 1437 .
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 .
Fujimoto A , Hiramoto N , Yamasaki S , et al . Risk factors and predictive scoring system for post-transplant lymphoproliferative disorder after hematopoietic stem cell transplantation [J ] . Biol Blood Marrow Transplant , 2019 , 25 ( 7 ): 1441 - 1449 .
Lindsay J , Othman J , Heldman MR , et al . Epstein-Barr virus posttransplant lymphoproliferative disorder:update on management and outcomes [J ] . Curr Opin Infect Dis , 2021 , 34 ( 6 ): 635 - 645 .
Kinzel M , Dowhan M , Kalra A , et al . Risk factors for the incidence of and the mortality due to post-transplant lymphoproliferative disorder after hematopoietic cell transplantation [J ] . Transplant Cell Ther , 2022 , 28 ( 1 ): 53.e1 - 53.53 .e10.
DeStefano CB , Desai SH , Shenoy AG , et al . Management of post-transplant lymphoproliferative disorders [J ] . Br J Haematol , 2018 , 182 ( 3 ): 330 - 343 .
Leeman-Neill RJ , Soderquist CR , Montanari F , et al . Phenogenomic heterogeneity of post-transplant plasmablastic lymphomas [J ] . Haematologica , 2022 , 107 ( 1 ): 201 - 210 .
Zaffiri L , Chambers ET . Screening and management of PTLD [J ] . Transplantation , 2023 , 107 ( 11 ): 2316 - 2328 .
Samant H , Vaitla P , Kothadia JP . Posttransplant lymphoproliferative disorders [J ] . StatPearls Publishing , 2023 .
Zimmermann H , Nitsche M , Pott C , et al . Reduction of immunosuppression combined with whole-brain radiotherapy and concurrent systemic rituximab is an effective yet toxic treatment of primary central nervous system post-transplant lymphoproliferative disorder(pCNS-PTLD):14 cases from the prospective German PTLD registry [J ] . Ann Hematol , 2021 , 100 ( 8 ): 2043 - 2050 .
Kim BK , Kang HJ , Hong KT , et al . Successful preemptive therapy with single-dose rituximab for Epstein-Barr virus infection to prevent post-transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation [J ] . Transpl Infect Dis , 2019 , 21 ( 6 ): e13182 .
Atallah-Yunes SA , Salman O , Robertson MJ . Post-transplant lymphoproliferative disorder:update on treatment and novel therapies [J ] . Br J Haematol , 2023 , 201 ( 3 ): 383 - 395 .
Liu L , Liu QF , Feng SZ . Management of Epstein-Barr virus-related post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation [J ] . Ther Adv Hematol , 2020 , 11 : 2040620720910964 .
Prockop S , Doubrovina E , Suser S , et al . Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation [J ] . J Clin Invest , 2020 , 130 ( 2 ): 733 - 747 .
Van Besien K , Bachier-Rodriguez L , Satlin M , et al . Prophylactic rituximab prevents EBV PTLD in haplo-cord transplant recipients at high risk [J ] . Leuk Lymphoma , 2019 , 60 ( 7 ): 1693 - 1696 .
Zhu CY , Zhao SS , Wang XK , et al . Outcome of rituximab-based treatment for post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation:a single-center experience [J ] . Ann Transplant , 2019 , 24 : 175 - 184 .
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 .
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 .
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