Abstract A 57-year-old male with stage IV diffuse large B-cell lymphoma (DLBCL), non-germinal center subtype, underwent 6 cycles of polatuzumab, rituximab, cyclophosphamide, doxorubicin, prednisone, and pegfilgrastim (Pola-R-CHP) then presented to the hospital with progressive confusion, double vision, hearing loss, and lower extremity weakness. MRI of the brain and spinal cord with and without IV contrast revealed extensive leptomeningeal enhancement along the brain, several cranial nerves, cervical and thoracic spinal cord with enhancement of the cauda equina. Cerebrospinal fluid (CSF) analysis studies revealed 41 nucleated cells/mm3, protein to 264 mg/dL, and an initial cryptococcal antigen titer of 1:1280; serial lumbar punctures peaked at an opening pressure of 39.5 cm H2O before improvement. Flow cytometry was negative on two CSF studies. Multiple cultures grew Cryptococcus neoformans before sterilization of CSF culture on day 13. He received induction therapy for 4 weeks with amphotericin B and flucytosine. Flucytosine treatment was limited due to cytopenias on day 9 and continued induction with amphotericin B and fluconazole. Fluconazole was switched for voriconazole based on minimal inhibitory concentrations by broth dilution, however, the drug was undetectable on therapeutic drug monitoring 2 weeks later and switched back to fluconazole. Subsequent positron emission tomography revealed ongoing hypermetabolic thoracic, mediastinal, and hilar lymph nodes compared to PET scans prior to chemotherapy for which he underwent transbronchial fine needle aspiration concerning for Cryptococcus involvement. He remained on fluconazole 800mg/day and MRI 11 months after the initial presentation demonstrated ongoing but slightly improved leptomeningeal enhancement. Due to persistent symptoms despite sterile CSF cultures, he underwent a three-day course of IV methylprednisolone 1000mg with some incomplete improvement in symptoms. The opening pressure normalized and the cryptococcal antigen titer decreased to 1:20 about 11 months after initial treatment. This case highlights the risk of opportunistic infections like cryptococcal meningitis in patients undergoing chemotherapy.
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