Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection

Colin D. Hall, Urania Dafni, David Simpson, David Clifford, Patricia E. Wetherill, Bruce Cohen, Justin Charles McArthur, Harry Hollander, Constantin Yainnoutsos, Eugene Major, Linda Millar, Joseph Timpone

Research output: Contribution to journalArticle

Abstract

Background: Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine. Methods: In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine. Results: At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences 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 patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups. Conclusions: Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

Original languageEnglish (US)
Pages (from-to)1345-1351
Number of pages7
JournalNew England Journal of Medicine
Volume338
Issue number19
DOIs
StatePublished - May 7 1998

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Progressive Multifocal Leukoencephalopathy
Cytarabine
Virus Diseases
HIV
Therapeutics
Survival
Anti-Retroviral Agents
Stavudine
Didanosine
Leukoencephalopathies
Zidovudine
Thrombocytopenia
Multicenter Studies
Anemia
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Medicine(all)

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Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. / Hall, Colin D.; Dafni, Urania; Simpson, David; Clifford, David; Wetherill, Patricia E.; Cohen, Bruce; McArthur, Justin Charles; Hollander, Harry; Yainnoutsos, Constantin; Major, Eugene; Millar, Linda; Timpone, Joseph.

In: New England Journal of Medicine, Vol. 338, No. 19, 07.05.1998, p. 1345-1351.

Research output: Contribution to journalArticle

Hall, CD, Dafni, U, Simpson, D, Clifford, D, Wetherill, PE, Cohen, B, McArthur, JC, Hollander, H, Yainnoutsos, C, Major, E, Millar, L & Timpone, J 1998, 'Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection', New England Journal of Medicine, vol. 338, no. 19, pp. 1345-1351. https://doi.org/10.1056/NEJM199805073381903
Hall, Colin D. ; Dafni, Urania ; Simpson, David ; Clifford, David ; Wetherill, Patricia E. ; Cohen, Bruce ; McArthur, Justin Charles ; Hollander, Harry ; Yainnoutsos, Constantin ; Major, Eugene ; Millar, Linda ; Timpone, Joseph. / Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. In: New England Journal of Medicine. 1998 ; Vol. 338, No. 19. pp. 1345-1351.
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AU - Dafni, Urania

AU - Simpson, David

AU - Clifford, David

AU - Wetherill, Patricia E.

AU - Cohen, Bruce

AU - McArthur, Justin Charles

AU - Hollander, Harry

AU - Yainnoutsos, Constantin

AU - Major, Eugene

AU - Millar, Linda

AU - Timpone, Joseph

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N2 - Background: Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine. Methods: In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine. Results: At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences 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 patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups. Conclusions: Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

AB - Background: Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine. Methods: In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine. Results: At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences 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 patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups. Conclusions: Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

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