BACKGROUND The use of monoclonal antibodies in various settings has been linked to the development of progressive multifocal leukoencephalopathy (PML). Whilst this association is well-described with agents such as rituximab and natalizumab, the literature describing the occurrence of PML with ofatumumab therapy (especially in a haematology setting) is sparse. This case aims to draw attention to the above association with a particular focus on the mechanisms by which B-cell-depleting therapy can precipitate PML during the treatment of haematological malignancy. CASE PRESENTATION A 68-year-old Caucasian man presented with acute-on-subacute confusion and reduced mobility. He had a history of chronic lymphocytic leukaemia for which he had completed six cycles of ofatumumab and chlorambucil 2 months prior to presentation. Biochemistry, physical examination and imaging were unremarkable on admission. Subsequent neurological examination demonstrated diminished reflexes and an extensor right plantar, while magnetic resonance imaging (MRI) assessment revealed white matter hyperintensities in the frontal lobes with restricted diffusion surrounding these areas. Cerebrospinal fluid (CSF) analysis demonstrated normal cell counts and chemistry but detected John Cunningham virus (JCV) via polymerase chain reaction (PCR), with a quantitative value of 41,850 gEg/ml. CSF immunophenotyping excluded malignant processes. A diagnosis of PML was confirmed, and with the support of palliative care, the patient was discharged to a hospice for ongoing care with the family's agreement. CONCLUSION PML remains a rare complication of ofatumumab treatment. Nevertheless, clinicians should maintain a certain level of suspicion for this risk, especially in the context of patients presenting with clinical syndromes of encephalopathy and focal neurologic deficits. Furthermore, research to better our understanding of the manifold links between B-cell function and JCV regulation could provide valuable information for use in the future prevention and treatment of PML.

中文翻译：

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慢性淋巴细胞性白血病患者的快速认知功能下降：病例报告。

背景技术在各种情况下使用单克隆抗体已经与进行性多灶性白质脑病（PML）的发展有关。尽管用利妥昔单抗和那他珠单抗等药物对此关联进行了很好的描述，但描述奥法妥单抗治疗（特别是在血液学方面）发生PML的文献很少。本案例旨在引起人们对上述关联的关注，特别关注血液细胞恶性肿瘤治疗过程中B细胞耗竭疗法可沉淀PML的机制。病例介绍一名68岁的白种男人表现出亚急性急性意识模糊和行动不便。他有慢性淋巴细胞性白血病病史，在就诊前两个月已完成ofatumumab和苯丁酸氮芥的六个周期。生物化学 入院时体检和影像学检查无异常。随后的神经系统检查显示反射减弱，右足底伸肌，而磁共振成像（MRI）评估显示额叶白质高信号，这些区域周围扩散受限。脑脊液（CSF）分析显示细胞计数和化学反应正常，但通过聚合酶链反应（PCR）检测到约翰·坎宁安病毒（JCV），定量值为41,850 gEg / ml。脑脊液免疫表型排除恶性过程。确诊为PML，并在姑息治疗的支持下，经家庭同意，患者被送往临终关怀医院接受持续治疗。结论PML仍然是ofatumumab治疗的罕见并发症。不过，临床医生应对这种风险保持一定程度的怀疑，尤其是在出现脑病和局灶性神经功能缺损的临床综合征的患者中。此外，为更好地了解B细胞功能与JCV调节之间的多重联系而进行的研究可能会为将来预防和治疗PML提供有用的信息。