Progressive multifocal leukoencephalopathy in a patient with chronic lymphocytic leukaemia treated with alemtuzumab

Abstract

A 69-year-old Caucasian woman with a 15-year history of refractory chronic lymphocytic B-cell leukaemia (CLL), treated with alemtuzumab in the past 10 months presented with a subacute right foot drop. Initial evaluation with a brain CT scan, lumbosacral MRI, nerve conduction studies and LP was negative. In the following months, progressive right hemibody weakness and dysarthria developed. Brain MRI showed a bilateral parasagittal frontal lesion. Alemtuzumab treatment was withdrawn. Progressive multifocal leukoencephalopathy (PML) was confirmed by PCR. Attempted antiviral therapies proved fruitless. Inexorable clinical deterioration ensued and the patient passed away 10 months after the presentation. This case report intends to call attention for PML as a potential fatal complication of severe immunosuppression, including the possible role of new monoclonal antibodies (such as alemtuzumab) in its pathogenesis.

Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis

“…The details about five of these cases have been published. Four instances of PML occurred in patients diagnosed with chronic lymphocytic leukemia [53][54][55][56]. The other case occurred in a lung transplant patient who was receiving prednisone, azathioprine and tacrolimus.…”

“…However, patients using the drug for other indications have been diagnosed with the infection. A review of the World Health Organization Collaborating Center for International Monitoring Adverse Events data bank revealed 14 reported cases of PML in alemtuzumab users [53]. The details about five of these cases have been published.…”

“…Alemtuzumab was administered as part of a treatment regimen for allograft rejection [26]. The onset of PML with alemtuzumab exposure seems to occur quite rapidly, as the mean latency to diagnosis in the 14 reported patients was approximately 1 month from treatment initiation [53].…”

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis

“…Some instances of herpes virus reactivation have been observed (but no encephalitis) so that prophylactic aciclovir treatment is considered obligatory in the first 4 weeks after treatment initiation. Cases of PML have not been reported thus far in patients with MS, but only in hematological and transplantation indications [71][72][73]. Cases of listeria infections have been reported, some with a severe disease course [74].…”

Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie

“…Außerdem sind unter der Substanz Fäl-le von PML bei Patienten mit CLL oder Non-Hodgkin-Lymphom im Rahmen einer Kombinationstherapie und unter einer höheren Dosierung aufgetreten [44].…”