Case report: Acute HHV6B encephalitis/myelitis post CAR-T cell therapy in patients with relapsed/refractory aggressive B-cell lymphoma
Case report: Acute HHV6B encephalitis/myelitis post CAR-T cell therapy in patients with relapsed/refractory aggressive B-cell lymphoma
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DOI：
10.3389/fneur.2024.1334000
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发表时间：
2024-02
影响因子：
3.4
通讯作者：
Ningwen Li;Ruoxuan Zhang;Jue Wang;Xiaojian Zhu;Fankai Meng;Yang Cao;Gaoxiang Wang;Yang Yang-Yang
中科院分区：
文献类型：
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作者：
Ningwen Li;Ruoxuan Zhang;Jue Wang;Xiaojian Zhu;Fankai Meng;Yang Cao;Gaoxiang Wang;Yang Yang-Yang
背景 嵌合抗原受体 (CAR)-T 细胞疗法的发展彻底改变了淋巴恶性肿瘤患者的治疗结果。然而，一些研究报告称，接受 CD19 靶向 CAR T 细胞治疗的成年患者的感染率相对较高，特别是在前 28 天。值得注意的是，多达三分之二的异体造血干细胞移植患者会出现急性人类疱疹病毒 6 B (HHV6B) 重新激活。病例介绍 在此，我们描述了三名 CAR T 细胞治疗后复发/难治性弥漫性大 B 细胞淋巴瘤患者发生 HHV6B 脑炎/脊髓炎的报告。所有三名患者均接受过多线既往治疗（范围：2-9 线）。所有患者均在 CAR-T 细胞输注 (CTI) 后出现持续至少 2 周的发烧症状。发病时间和持续时间均与细胞因子释放综合征（CRS）相似；然而，患者的 CRS 等级较低（1 级或 2 级）。 CTI 后的谵妄和记忆丧失是最早值得注意的精神表现。神经系统症状进展迅速，患者出现不同程度的意识障碍、癫痫发作和昏迷。 3号患者还出现背痛、腰痛、下肢无力和尿潴留，提示有脊髓炎。使用宏基因组下一代测序 (mNGS) 在所有脑脊液 (CSF) 样本中检测到高 HHV6B 负载。只有一名患者需要高活性抗病毒药物和IgG静脉脉冲治疗最终康复，而另外两名患者则死于HHV6B脑炎。结论 考虑到其致命性，HHV6B 脑炎/脊髓炎应在 CAR-T 细胞治疗后紧急诊断。此外，血液学家应尽早将这些病症与 CRS 或其他免疫治疗相关的神经毒性进行鉴别诊断。这项研究的结果证明了 mNGS 在 HHV6B 感染早期诊断中的潜力，特别是当微生物难以培养时。
Background The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized treatment outcomes in patients with lymphoid malignancies. However, several studies have reported a relatively high rate of infection in adult patients following CD19-targeting CAR T-cell therapy, particularly in the first 28 days. Notably, acute human herpesvirus 6 B (HHV6B) reactivation occurs in up to two-thirds of allogeneic hematopoietic stem cell transplantation patients. Case presentations Herein, we describe a report of HHV6B encephalitis/myelitis in three patients with relapsed/refractory diffuse large B-cell lymphoma post CAR T-cell therapy. All three patients received multiple lines of prior treatment (range: 2–9 lines). All patients presented with fever that persisted for at least 2 weeks after CAR-T cell infusion (CTI). Both the onset time and duration were similar to those of the cytokine release syndrome (CRS); nevertheless, the CRS grades of the patients were low (grade 1 or 2). Delirium and memory loss after CTI were the earliest notable mental presentations. Neurological manifestations progressed rapidly, with patients experiencing varying degrees of impaired consciousness, seizures, and coma. Back pain, lumbago, lower limb weakness and uroschesis were also observed in Patient 3, indicating myelitis. High HHV6B loads were detected in all Cerebral spinal fluid (CSF) samples using metagenomic next-generation sequencing (mNGS). Only one patient required high-activity antivirals and IgG intravenous pulse treatment finally recovered, whereas the other two patients died from HHV6B encephalitis. Conclusion Considering its fatal potential, HHV6B encephalitis/myelitis should be urgently diagnosed post CAR-T cell-based therapy. Furthermore, hematologists should differentially diagnose these conditions from CRS or other immunotherapy-related neurotoxicities as early as possible. The results of this study demonstrate the potential of mNGS in the early diagnosis of HHV6B infection, particularly when the organism is difficult to culture.