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血浆 EBV-DNA 载量和 EBER 状态在新诊断的外周 T 细胞淋巴瘤中的作用。

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma.

机构信息

Bone Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Pathology Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

出版信息

J Cancer Res Clin Oncol. 2024 Apr 8;150(4):181. doi: 10.1007/s00432-024-05702-9.

Abstract

PURPOSE

To explore the prognostic and therapeutic role of Epstein-Barr Virus (EBV) on peripheral T-cell lymphoma (PTCL).

METHODS

Totally 262 newly diagnosed PTCL patients who were hospitalized from January 2014 to December 2022 were retrospectively enrolled. Molecular analysis included 31 eligible patients. EBV-encoded RNA (EBER) presence in tumor tissue and EBV DNA levels in patients at baseline (DNA1) and after 4 cycles of chemotherapy (DNA4) were assessed.

RESULTS

Our findings revealed that the EBER-positive cohort exhibited significant differences compared to counterparts in overall survival (OS, P = 0.047) and progression-free survival (PFS, P = 0.009). Both DNA1 and DNA4 were significantly associated with inferior OS. Multivariate analysis demonstrated that DNA4 independently affected PTCL prognosis for OS (hazard ratio = 5.1617; 95% confidence interval 1.1017-24.1831; P = 0.037). Treatment with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus azacytidine regimen showed a better OS compared to CHOP or CHOP plus etoposide for patients with partially positive EBER and EBER positive statuses (P = 0.192), although the improvement was not statistically significant. This study delineated the genetic paradigm of PTCL, comparing genetic differences by EBV status and found that EBER partially positive plus positive patients were more likely to have DNMT3A (P = 0.002), RHOA (P = 0.023), and TET2 mutations (P = 0.032).

CONCLUSION

EBER, DNA1, and DNA4 emerged as sensitive markers for prognosis. CHOP plus azacytidine might present a preferable option for PTCL patients with DNA methylation due to EBV infection.

摘要

目的

探索 Epstein-Barr 病毒(EBV)在外周 T 细胞淋巴瘤(PTCL)中的预后和治疗作用。

方法

回顾性纳入 2014 年 1 月至 2022 年 12 月期间住院的 262 例新诊断的 PTCL 患者。分子分析包括 31 例合格患者。评估肿瘤组织中 EBV 编码 RNA(EBER)的存在以及患者基线时(DNA1)和化疗 4 周期后(DNA4)的 EBV DNA 水平。

结果

我们的研究结果表明,EBER 阳性组在总生存期(OS,P = 0.047)和无进展生存期(PFS,P = 0.009)方面与对照组存在显著差异。DNA1 和 DNA4 均与 OS 显著相关。多变量分析表明,DNA4 独立影响 PTCL 的 OS 预后(风险比=5.1617;95%置信区间 1.1017-24.1831;P = 0.037)。与 CHOP 或 CHOP 加依托泊苷相比,对于 EBER 部分阳性和 EBER 阳性状态的患者,使用环磷酰胺、多柔比星、长春新碱和泼尼松(CHOP)加阿扎胞苷方案治疗具有更好的 OS(P = 0.192),尽管改善不具有统计学意义。本研究描绘了 PTCL 的遗传模式,通过 EBV 状态比较遗传差异,发现 EBER 部分阳性加阳性患者更有可能发生 DNMT3A(P = 0.002)、RHOA(P = 0.023)和 TET2 突变(P = 0.032)。

结论

EBER、DNA1 和 DNA4 是预后的敏感标志物。由于 EBV 感染,CHOP 加阿扎胞苷可能为 DNA 甲基化的 PTCL 患者提供更好的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97cf/11793215/46cc3ec8ec2c/432_2024_5702_Fig1_HTML.jpg

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