Due to further neurologic deterioration, she was admitted to an outside hospital. progressive multifocal leukoencephalopathy (PML) (physique, J). The patient was discharged home with hospice care. Upon discharge, she was started on prednisone 50 mg daily to help treat her eczema. Her family brought her to our clinic for a second opinion. A 38-year-old woman was diagnosed with cutaneous anaplastic T-cell lymphoma that proved refractory to methotrexate, bexarotene, denileukin diftitox, interferon -1b, interferon -2b, vorinostat, and pralatrexate. She was therefore started around the newly approved monoclonal anti-CD30 antibody brentuximab vedotin. Treatment with brentuximab 1.8 mg/kg IV every 3 weeks quickly Cot inhibitor-2 led to disappearance of her cutaneous tumors. The day after her second brentuximab infusion she developed word-finding difficulties and unsteady gait. Due to further neurologic deterioration, she was admitted to an outside hospital. Brain MRI revealed multifocal enhancing white matter lesions Cot inhibitor-2 throughout bilateral cerebral hemispheres and posterior fossa (physique, ACC). Brain biopsy was performed 15 days after her last brentuximab dose to rule out metastases and she was diagnosed with progressive multifocal leukoencephalopathy (PML) (physique, J). The patient was discharged home with hospice care. Upon discharge, she was started on prednisone 50 mg daily to help treat her eczema. Her family brought her to our clinic for a second opinion. Open in a separate window Physique Radiographic and pathologic evidence of progressive multifocal leukoencephalopathy and progressive multifocal leukoencephalopathyCimmune reconstitution inflammatory syndrome(ACI) Axial MRI over time shows worsening of signal abnormality on fluid-attenuated inversion recovery (FLAIR) (top 2 rows) at 2 months (D, E) compared to initial presentation (A, B) with some improvement at 3 months (G, H). There is significant increase in gadolinium enhancement 2 months after initial presentation (F) compared to initial imaging (C), which is essentially unchanged at 3 months (I). (JCL) Left frontal brain biopsy reveals subsets of large gemistocytic astrocytes and oligodendrocytes with prominent nuclear enlargement that were positive after immunostaining with a polyclonal antibody against JC virus (Santa Cruz Immunochemicals, Santa. Cruz, CA) (J). Multiple infiltrating T cells are Cot inhibitor-2 seen on immunohistochemistry staining for CD4 (K) and CD3 (L). The patient presented to us with a mixed nonfluent aphasia, moderate apraxia, 4/5 strength in all extremities, and gait ataxia that required one person assist. Repeat brain MRI exhibited worsening white matter lesions and contrast enhancement, concerning for immune reconstitution inflammatory syndrome (IRIS) (physique, DCF). Additional immunostaining of her brain biopsy was performed, which exhibited a mixed population of T-cell infiltrates with a predominance of CD4+ T-cells (physique, K and L). We continued her on high-dose oral corticosteroids for suspected PML-IRIS. Since she had not received brentuximab in more than 8 weeks, we opted not to initiate plasma exchange therapy. Over the ensuing weeks, our patient demonstrated slow but definite improvement. She is currently ambulating without assistance and has increased spontaneous speech and comprehension. Her most recent brain MRI showed decreased GAL lesion load and reduced enhancement (physique, GCI). She continues to be followed closely clinically and with frequent MRIs. DiscussionRecently, PML has been seen in an increasing number of patients receiving monoclonal antibodies. Most prominently, it has been described in patients with multiple sclerosis receiving natalizumab, an -4 integrin blocker.1 However, PML has also occurred in patients receiving other immunomodulatory therapies.2 Several cases have been reported in patients around the B-cell-depleting anti-CD20 antibody, rituximab, and the adhesion molecule inhibitor, efalizumab, which binds the -1 integrin CD11a.3 The Food and Drug Administration recently added a black box warning to the package insert of brentuximab in response to the statement of 2 additional instances of PML that were associated with this medication (included our patient). Brentuximab is an antibody-drug conjugate linking the antimicrotubule agent monomethyl auristatin E to a CD30 monoclonal antibody. CD30 (TNFSR8) is frequently indicated on anaplastic large-cell lymphoma cells as well as with Hodgkin lymphoma.4 It is not amazing that alterations in immune cellular function can lead to PML; however,.