FAILURE OF CYTARABINE IN PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY ASSOCIATED WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Background Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS) , and survival after the diagnosis of leukoencephalopathy averages onl y about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plu s intravenous or intrathecal cytarabine.Methods In this multicenter tr ial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were rand omly assigned to receive one of three treatments: antiretroviral thera py alone, antiretroviral therapy plus intravenous cytarabine, or antir etroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most pat ients, antiretroviral therapy consisted of zidovudine plus either dida nosine or stavudine. Results At the time of the last analysis, 14 pati ents in each treatment group had died, and there were no significant d ifferences in survival among the three groups (P=0.85 by the log-rank test). The median survival times (11, 8, and 15 weeks) were similar to those in previous studies. Only seven patients completed the 24 weeks of treatment. Anemia and thrombocytopenia were more frequent in patie nts who received antiretroviral therapy in combination with intravenou s cytarabine than in the other groups. Conclusions Cytarabine administ ered either intravenously or intrathecally does not improve the progno sis of HIV-infected patients with progressive multifocal leukoencephal opathy who are treated with the antiretroviral agents we used, nor doe s high-dose antiretroviral therapy alone appear to improve survival ov er that reported in untreated patients. (C)1998, Massachusetts Medical Society.