Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
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Case Report

Volume 10, Number 5, October 2021, pages 212-216

Progressive Multifocal Leukoencephalopathy After Chimeric Antigen Receptor T-Cell Therapy for Recurrent Non-Hodgkin Lymphoma

Figures

Figure 1.
Figure 1. Serum immunoglobulin (IgG) levels and CD4 T-cell counts in response to various lymphoma treatments. A steady decline in serum IgG levels (black) and absolute CD4 counts (red), reaching a nadir after infusion of CD19-targeted CAR T-cells in May 2017. Absolute CD8 counts (green) were relatively preserved. R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; ICE: ifosfamide, carboplatin, etoposide; Auto-SCT: autologous stem cell transplant; R-benda: rituximab, bendamustine; CAR: chimeric antigen receptor; Pembro + IVIG: pembrolizumab, intravenous immunoglobulin; CD: cluster of differentiation.
Figure 2.
Figure 2. Magnetic resonance imaging evolution and brain biopsy. (a) FLAIR signal abnormality was absent in May 2017 at the time of CAR T-cell infusion and prior to onset of neurological symptoms. (b) FLAIR signal abnormality in the left occipital lobe at the time of initial presentation for visual disturbance in April 2018 (red circle). (c) Expansion of FLAIR signal (red arrows) involving the left occipital lobe and left posterior temporal lobe in April 2019 after presentation with progressive word finding difficulty. Hematoxylin and eosin (H&E) stained sections from left occipital brain biopsy show (d) bizarre-appearing astrocytes and violaceous oligodendroglial nuclear inclusions (inset). Immunohistochemistry demonstrates strong nuclear positivity for SV-40 (e). White scale bars = 100 µm.

Table

Table 1. Review of Prior Reports of Progressive Multifocal Leukoencephalopathy (PML) After CAR T-Cell Therapy
 
ReferenceAge/sexCAR T-cellsPresenting neurologic symptoms (intervala)Outcome
aInterval from CAR T-cell administration to neurologic symptom onset. CAR: chimeric antigen receptor; F: female; PML: progressive multifocal leukoencephalopathy.
Sdrimas et al, 2020 [12]68/FAxicabtagene ciloleucel (Axi-cel)Confusion, aphasia, ataxia, involuntary movements (7 months)Alive and stable, 12 months after PML diagnosis
Mian et al, 2021 [13]61/FAxicabtagene ciloleucel (Axi-cel)Unsteady gait, dysarthria, loss of taste (14 months)Deceased, 1 month after PML diagnosis
Current case68/FLisocabtagene maraleucel (Liso-cel)Visual deficits (11 months); word finding difficulty and worsening visual deficits (23 months)Deceased, 2 months after PML diagnosis