PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■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,一些研究报道，在CD19靶向CAR-T细胞治疗后，成人患者的感染率相对较高，尤其是前28天。值得注意的是,急性人类疱疹病毒6B（HHV6B）再激活发生在多达三分之二的异基因造血干细胞移植患者中。
■这里，我们描述了3例复发/难治性弥漫性大B细胞淋巴瘤患者接受CAR-T细胞治疗后发生HHV6B脑炎/脊髓炎的报告.所有三名患者均接受多行先前治疗（范围：2-9行）。所有患者在CAR-T细胞输注（CTI）后持续发热至少2周。发病时间和持续时间与细胞因子释放综合征（CRS）相似；然而，患者的CRS分级较低(1级或2级).CTI后的谵妄和记忆丧失是最早值得注意的心理表现。神经系统表现进展迅速，患者经历不同程度的意识障碍，癫痫发作,和昏迷。背痛,腰痛,患者3还观察到下肢无力和尿潴留，表明脊髓炎。使用宏基因组下一代测序（mNGS）在所有脑脊液（CSF）样品中检测到高HHV6B负荷。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，而另外两名患者死于HHV6B脑炎。
■考虑到它的致命潜力，HHV6B脑炎/脊髓炎应在CAR-T细胞治疗后紧急诊断。此外，血液科医师应尽早将这些疾病与CRS或其他免疫疗法相关的神经毒性进行鉴别诊断。这项研究的结果表明mNGS在HHV6B感染的早期诊断中的潜力，特别是当生物体难以培养时。
■这里，我们描述了3例复发/难治性弥漫性大B细胞淋巴瘤患者接受CAR-T细胞治疗后发生HHV6B脑炎/脊髓炎的报告.所有三名患者均接受多行先前治疗（范围：2-9行）。所有患者在CAR-T细胞输注（CTI）后持续发热至少2周。发病时间和持续时间与细胞因子释放综合征（CRS）相似；然而，患者的CRS分级较低(1级或2级).CTI后的谵妄和记忆丧失是最早值得注意的心理表现。神经系统表现进展迅速，患者经历不同程度的意识障碍，癫痫发作,和昏迷。背痛,腰痛,患者3还观察到下肢无力和尿潴留，表明脊髓炎。使用宏基因组下一代测序（mNGS）在所有脑脊液（CSF）样品中检测到高HHV6B负荷。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，而另外两名患者死于HHV6B脑炎。
■考虑到它的致命潜力，HHV6B脑炎/脊髓炎应在CAR-T细胞治疗后紧急诊断。此外，血液科医师应尽早将这些疾病与CRS或其他免疫疗法相关的神经毒性进行鉴别诊断。这项研究的结果表明mNGS在HHV6B感染的早期诊断中的潜力，特别是当生物体难以培养时。
