Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: report of two Japanese patients without human immunodeficiency virus infection.

Abstract Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. We report on the failure of mefloquine therapy in two Japanese patients with PML unrelated to human immunodeficiency virus. One of the patients was a 47-year-old male who had been treated with chemotherapy for Waldenstrom macroglobulinemia, and the other was an 81-year-old male with idiopathic CD4 + lymphocytopenia. Diagnosis of PML was established based on MRI findings and increased JC virus DNA in the cerebrospinal fluid in both patients. Mefloquine was initiated about 5 months and 2 months after the onset of PML, respectively. During mefloquine therapy, clinical and radiological progression was observed, and JC virus DNA in the cerebrospinal fluid was increased in both patients. Both patients died about 4 months and 2 months after initiation of mefloquine, respectively. Further studies are necessary to clarify the differences between mefloquine responders and non-responders in PML.