BK polyomavirus-associated progressive multifocal leukoencephalopathy following mogamulizumab therapy for erythrodermic mycosis fungoides

Introduction BK polyomavirus (BKPyV) is a ubiquitous human pathogen that typically causes nephropathy and hemorrhagic cystitis in immunocompromised patients. Although BKPyV shares close genetic and structural similarity with JC polyomavirus (JCPyV), which is responsible for progressive multifocal leukoencephalopathy (PML), its neurotropic potential remains poorly characterized. Rare reports have suggested possible central nervous system (CNS) involvement under conditions of severe immune suppression. Here, we describe the first documented case of BKPyV-associated PML in a patient with erythrodermic mycosis fungoides treated with Mogamulizumab, a CCR4-targeting monoclonal antibody that profoundly alters immune surveillance. Results We describe a patient with erythrodermic mycosis fungoides and long-standing immunological frailty, who developed neurological symptoms during Mogamulizumab therapy. Brain MRI showed multifocal white matter lesions compatible with PML. BKPyV DNA was detected in plasma, urine, and cerebrospinal fluid (CSF), while JCPyV DNA was absent. Serological testing showed high anti-BKPyV and anti-JCPyV IgG levels in plasma, indicating prior exposure to both viruses, while antibodies were undetectable in CSF, consistent with lack of intrathecal synthesis. This compartmental dissociation between plasma and CSF, together with the detection of BKPyV DNA and the absence of JCPyV DNA in CSF, supports BKPyV as the etiological neurotropic agent responsible for leukoencephalopathy. Sequencing of the VP1 and NCCR regions revealed compartment-specific nucleotide and amino acid variants, including non-conservative substitutions in the CSF isolate, suggesting intra-host viral heterogeneity. Compartment-specific sequence variability of viral protein 1 (VP1) and structural rearrangements of the non-coding control region (NCCR), particularly the loss of the Q and R block in CSF-derived isolates, underscore intra-host heterogeneity of BKV and may contribute to its adaptation and neurotropic potential. Conclusion This is the first documented case of BKPyV-associated PML in a Mogamulizumab-treated patient. These findings highlight intra-host heterogeneity at the protein level, possibly reflecting compartment-specific viral evolution, and underscore the need for vigilant BKPyV and JCPyV monitoring during Mogamulizumab treatment.