Progressive multifocal leukoencephalopathy following five lines of therapy and three autologous bone marrow transplants for multiple myeloma

Abstract

A 59-year-old man, with a background of multiply relapsed myeloma, presented with a 3-week history of confusion, short-term memory impairment and behavioural changes. CT head showed bilateral white matter changes and numerous, large lytic lesions of the skull vault. MRI brain revealed multiple areas of hyperintensity on T2-weighted sequences which did not enhance (many of which showed diffusion restriction) unexpectedly bringing progressive multifocal leukoencephalopathy (PML) into the differential. Initial cerebrospinal fluid studies were largely unremarkable, aside from a mildly elevated protein; cultures were negative. PCR for the John Cunningham (JC) virus was positive. Considering the patient’s medical history and rapidily progressive symptoms, a palliative approach was adopted, with the patient dying 14 days later. We present this case as an example of PML in a patient with multiple myeloma, highlighting the need to consider this diagnosis in an enlarging population of heavily treated, severely immunocompromised, patients.

Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma

“…The presentation of leukoencephalopathy with demyelinating processes among patients with MM who are receiving active treatment generally prompts a differential diagnosis that includes meningoencephalitis, malignant CNS involvement, PML, posterior reversible encephalopathy syndrome (PRES), genetic leukodystrophy, and chemotherapy-induced leukoencephalopathy. [4][5][6][11][12][13] For the patients in our series, we ruled out infection and malignant cerebral involvement because of negative CSF results throughout their courses of therapy. A summary of the cases is presented in Table 1 with patient timelines in Figure 2.…”

“…1,2 In the setting of multiple myeloma (MM), leukoencephalopathy is rare and has been predominantly documented secondary to central nervous system (CNS) disease, paraneoplastic syndrome, infectious processes, genetic conditions, and medication use. [3][4][5][6] Leukoencephalopathy-primarily John Cunningham (JC) virus-associated progressive multifocal leukoencephalopathy (PML)-has been reported in association with monoclonal antibody treatment. 7 Daratumumab is a human monoclonal antibody that targets CD38, a cell surface glycoprotein that is highly expressed on myeloma cells.…”

Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy

“…Neither the patient with indolent IgA multiple myeloma nor the patient with Castleman's disease was treated with specific therapies. PML has been reported in patients with multiple myeloma but most cases were in patients with several lines of chemotherapy and/or autologous bone marrow transplants [22][23][24][25]. Only one case of PML revealing myeloma in a non-PWH has been reported [26].…”

Progressive multifocal leukoencephalopathy in multiple myeloma

“…2,3 The incidence, clinical features, and risk factors for PML in multiple myeloma patients are not firmly established. PML in multiple myeloma patients has been primarily described in sporadic case reports [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] A recent literature review identified 16 cases of PML that met AAN criteria between 1965 and April 2020. 25 Of these, most were published after 2016.…”