Department of Hematology, The First Affiliated Hospital of Nanchang University.
Department of Lymphomatous diseases, Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province.
Anticancer Drugs. 2022 Jan 1;33(1):e769-e775. doi: 10.1097/CAD.0000000000001187.
Epstein-Barr virus (EBV) is convincingly contributed to the development of several types of lymphomas such as NK/T cell lymphoma, Burkitt lymphoma, plasmablastic lymphoma, and diffuse large B cell lymphoma (DLBCL). Herein, we reported an atypical case of EBV-positive DLBCL in an immunocompetent young male patient who presented with epistaxis due to hypergammaglobulinemia. 2-Deoxy-2-[fluorine-8] fluoro-d-glucose PET/computed tomography showed multiple highly metabolic retroperitoneal tissue masses with the involvement of bilateral adrenal gland. Ultrasonography-guided biopsy revealed a significant number of lymphocytes and plasma-like cells that are immunopositive for plasma-cell markers and partly positive for pan-B cell markers. The Ki-67 proliferation index was 20%. The extensive distribution of EBV-encoded small RNAs was confirmed by in-situ hybridization. Due to atypical/overlapping pathological characteristics, it was initially misdiagnosed as extramedullary plasmacytoma and treated with two cycles of bortezomib, lenalidomide, and dexamethasone. Disease progression occurred and pathology consultation for the retroperitoneal biopsies modified the diagnosis to EBV-positive DLBCL with plasma cell differentiation. The treatment was adjusted to etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab, and lenalidomide (R2-EPOCH), but no response was observed after three cycles of treatment and he developed hemophagocytic syndrome during treatment. A monotherapy of anti-programmed cell death-1 (PD-1) treatment with tiririzumab was administered, successfully controlling hemophagocytic syndrome and EBV infection. The response assessment was partial for EBV-positive DLBCL, subsequent anti-CD19 chimeric antigen receptor-T (CAR-T) cell therapy resulted in complete remission including lumps, immunoglobulins, and negative EBV-DNA 1.5 months later. The present case study proved the possibility of PD-1 blockade in controlling EBV infection and associated hemophagocytic syndrome and offered an example of the combination of CAR-T therapy and PD-1 blockade for refractory EBV-positive DLBCL in clinic.
EBV 病毒（EBV）被认为与多种淋巴瘤的发展有关，如 NK/T 细胞淋巴瘤、伯基特淋巴瘤、浆母细胞淋巴瘤和弥漫性大 B 细胞淋巴瘤（DLBCL）。在此，我们报告了一例免疫功能正常的年轻男性 EBV 阳性 DLBCL 病例，该患者因高球蛋白血症而出现鼻出血。2-脱氧-2-[氟-8]氟代-D-葡萄糖 PET/CT 显示多个代谢活跃的腹膜后组织肿块，累及双侧肾上腺。超声引导活检显示大量淋巴细胞和浆样细胞，这些细胞免疫阳性表达浆细胞标志物，部分阳性表达泛 B 细胞标志物。Ki-67 增殖指数为 20%。原位杂交证实了 EBV 编码的小 RNA 的广泛分布。由于病理特征不典型/重叠，最初误诊为髓外浆细胞瘤，并接受了两周期硼替佐米、来那度胺和地塞米松治疗。疾病进展，对腹膜后活检进行病理会诊后，修改诊断为 EBV 阳性伴浆细胞分化的 DLBCL。治疗方案调整为依托泊苷、泼尼松、长春新碱、环磷酰胺、多柔比星、利妥昔单抗和来那度胺（R2-EPOCH），但治疗 3 个周期后未见反应，且在治疗过程中发生噬血细胞综合征。给予抗程序性死亡受体-1（PD-1）治疗单药替西利珠单抗治疗，成功控制噬血细胞综合征和 EBV 感染。对 EBV 阳性 DLBCL 的疗效评估为部分缓解，随后进行抗 CD19 嵌合抗原受体-T（CAR-T）细胞治疗，1.5 个月后肿块、免疫球蛋白和 EBV-DNA 均转阴，达到完全缓解。本病例研究证明了 PD-1 阻断在控制 EBV 感染和相关噬血细胞综合征方面的可能性，并为临床难治性 EBV 阳性 DLBCL 提供了 CAR-T 治疗与 PD-1 阻断联合应用的范例。
