Progressive multifocal leukoencephalopathy after first-line radiotherapy and temozolomide for glioblastoma
Authors: Alberto Picca, Clément Desjardins, Kévin Bihan, Nicolas Weiss, Amélie Guihot, Lucia Nichelli, Loic Feuvret, Valérie Pourcher, Mehdi Touat, Caroline Dehais
Journal: Neuro-Oncology (2022)

Progressive multifocal leukoencephalopathy after first-line radiotherapy and temozolomide for glioblastomaA 59-year-old woman was diagnosed with left fronto-temporooccipital glioblastoma (Figure 1a).After biopsy, she received two neo-adjuvant temozolomide (TMZ, 150-200 mg/m²) cycles as radiotherapy was delayed due to the emerging COVID pandemic.She eventually received standard chemoradiation (60 Gray in 30 fractions plus daily TMZ, 75 mg/m 2 , Figure 1b).She received oral methylprednisolone (16 mg/day) for a short period before and during chemoradiation.Baseline lymphocyte count was 3694/µL.After chemoradiation, partial clinicoradiological improvement was noticed (Figure 1c); Karnofsky performance status was 70, and her neurological examination mainly revealed a non-fluent aphasia.Shortly after the second adjuvant TMZ cycle (200 mg/ m 2 ), her neurological status rapidly declined with behavioral disorders in the foreground.This contrasted with brain MRI, which illustrated signs of oncological response with reduction in both tumor infiltration and mass effect.Electroencephalography did not show epileptic activity or typical encephalopathic patterns.An extensive screening, including testing of hepatic, renal, and thyroid function, ammonia, copper, folates, and vitamin levels, HIV and syphilis serologies, was unremarkable excepted for lymphopenia (770/μL) and moderately decreased vitamin B12 (132 pmol/L).CSF analysis displayed normal protein and glucose, one leukocyte per mm 3 , and was negative for herpes viruses by PCR.Intravenous B12 supplementation was initiated.The patient continued to deteriorate to a stuporous state, with a rapidly progressive left spastic hemiplegia, ipsilateral to the tumor.MRI was negative for tumor progression or cerebrovascular complications but showed a new hyperintense lesion involving the right internal capsule and the cortico-subcortical right frontal lobe on diffusionweighted sequences, compatible with a demyelination front (Figure 1d).This prompted repeated CSF analysis, which led to the identification of JC polyomavirus (JCV).A diagnosis of progressive multifocal leukoencephalopathy (PML) was established according to current criteria. 1Lymphocyte immunophenotyping disclosed severe CD4 + and B lymphocyte deficiency (50/µL and 43/µL, respectively).TMZ was definitively discontinued.The patient was discharged to a *Additional criteria apply.Please refer to protocol 14379-201 for full inclusion and exclusion criteria.† Patients can participate if they had some skin cancers, superficial bladder cancer (cancer that was only on the surface of the lining of the bladder), or carcinoma in situ (cancer that had not spread) of the cervix or breast that had been cured.HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; IGF-1R, insulin-like growth factor 1 receptor; KPS, Karnofsky Performance Scale; RT, radiotherapy; SOC, standard of care; TMZ, temozolomide.