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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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Front. Med.    2024, Vol. 18 Issue (2) : 394-398    https://doi.org/10.1007/s11684-023-1032-8
EBV-associated lymphoproliferative disease post-CAR-T cell therapy
Shiyuan Zhang1,2, Xiaoxi Zhou1,2, Shangkun Zhang3, Na Wang1,2, Tongcun Zhang3, Donghua Zhang1,2, Qilin Ao4(), Yang Cao1,2(), Liang Huang1,2,5,6()
1. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 430030, China
3. Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, China
4. Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
5. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
6. Tianjin Institutes of Health Science, Tianjin 301600, China
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Abstract

Epstein–Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT). However, their occurrence and treatment post-chimeric antigen receptor-modified T (CAR-T) cell therapy has not been reported. Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. After receiving CAR-T cell therapy in tandem with autologous HSCT, the patients achieved complete remission. However, with a median time of 38.5 months after CAR-T cell therapy, B-cell-derived EBV-LPDs were diagnosed, and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents. Collectively, our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy, especially in patients who previously had EBV-positive disorders, and they can be resolved by immune normalization strategy or B-cell depleting therapy.
Keywords EBV-associated lymphoproliferative disease      chimeric antigen receptor T-cell      autologous stem cell transplantation      immune checkpoint inhibitor     
Corresponding Author(s): Qilin Ao,Yang Cao,Liang Huang   
Just Accepted Date: 12 January 2024   Online First Date: 22 February 2024    Issue Date: 27 May 2024
 Cite this article:   
Shiyuan Zhang,Xiaoxi Zhou,Shangkun Zhang, et al. EBV-associated lymphoproliferative disease post-CAR-T cell therapy[J]. Front. Med., 2024, 18(2): 394-398.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-023-1032-8
https://academic.hep.com.cn/fmd/EN/Y2024/V18/I2/394
Fig.1  Lentiviral copies of CAR19 and CAR22 transgenes in peripheral blood after CAR-T cell infusion. (A) Lentiviral copies of CAR19 and CAR22 transgenes postinfusion in case 1. (B) Lentiviral copies of CAR19 and CAR22 transgenes postinfusion in case 2. Horizontal dotted line in each panel shows the lower limit of quantitation (50 copies/μg).
PatientAge (year)GenderInitial diagnosis, prognosis and immunohistochemistry (IHC)Prior treatmentsPathological features of EBV-LPDs
Case 133FemaleEBV + DLBCL, IPI = 2
IHC: CD19 (+), CD20 (+), CD22 (+), MUM-1 (+), Bcl-2 (+), BCL-6 (+), C-MYC (30% +), CD30 (partial +), PD-1 (partial +), Ki-67 (80% +), and EBER ISH (+)		R-CHOP, Gemox, R-ESHAP, R-DHAPPleomorphic B cell EBV-LPD, grade 2, with monoclonal plasmacytic hyperplasia
IHC: CD20 (partial +), CD79a (+), CD79b (+), CD19 (+), CD22 (+), MUM1 (+); EBER ISH (+)
Case 271MaleEBV + Burkitt, high riskIHC: CD19 (+), CD20 (+), CD22 (+), CD79a (+), MUM-1 (–), BCL-2 (–), BCL-6 (90% +), C-MYC (90% +), CD30 (–), Ki-67 (90% +), and EBER ISH (+ )R-DA-EPOCHPleomorphic B cell EBV-LPD, grade 2, with infiltration of reactive T cells
IHC: CD19 (+), MUM1 (+), CD20 (–), CD22 (–), CD79b (–); EBER ISH (+)
Tab.1  Clinical characteristics of the patients
Fig.2  Representative pathological changes in pleomorphic B cell EBV-LPD (case 1). (A) Hematoxylin and eosin (HE) staining of involved pharynx tissue (400×). (B) In situ hybridization (ISH) of EBER of involved pharynx tissue (200×). (C) HE staining of involved cervical lymph node (400×). (D) ISH of EBER of involved cervical lymph node (200×). (E) IHC staining of CD19 of involved cervical lymph node (100×). (F) IHC staining of CD79a involved in the cervical lymph node (100×).
Fig.3  Copy number changes in EBV-DNA in the plasma and PBMC before and after the diagnosis of EBV-LPDs.
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