A case of chronic lymphocytic leukemia with a paraneoplastic neurologic syndrome and leptomeningeal disease

Abstract Purpose Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by overproduction of monoclonal B cells. Paraneoplastic neurologic syndrome (PNS) and leptomeningeal disease (LMD) associated with CLL are both rare entities. We present a unique case that is, to our knowledge, the second reported case of CLL associated with Kelch-like protein 11– (KLHL11-) PNS and the first case of CLL with both LMD and KLHL11-PNS. Methods/results The patient was a 68-year-old woman who developed abdominal pain, nausea, vomiting, and vertigo. Imaging revealed retroperitoneal lymphadenopathy. After further studies, including flow cytometry, she was diagnosed with CLL. She received one dose of pembrolizumab with ibrutinib, and months later received three doses of Obinutuzumab, which were discontinued due to their side effects. The patient reported excessive fatigue, temporal headache, nausea, vomiting, vertigo, tremor of the upper extremities, and head bobbing. Lumbar puncture was positive for CLL cells, and the CSF paraneoplastic panel was positive for KLHL11 antibodies, with a titer of 1:64. She received intravenous immunoglobulin, intravenous methylprednisolone, plasmapheresis, intravenous rituximab, and Zanubrutinib, with minimal response. She was then prescribed intrathecal rituximab, which caused slight clinical improvement. Complete response was noted via CSF cytology. About 4 months later, she underwent Ommaya placement and received intraventricular rituximab. Her symptoms persisted despite improvement in CSF cytology, likely due to persistent PNS that was difficult to treat. Conclusion KLHL11-PNS is a rare disease entity that often evolves clinically into treatment-refractory rhombencephalitis. Though PNS and LMD management strategies may overlap, their clinical outcomes may be discordant.