PML therapy: "It's Déjà vu all over again".
PML therapy: "It's Déjà vu all over again".
复制标题
PML 疗法：“似曾相识的感觉又来了”。
DOI：
10.1007/s13365-013-0191-9
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发表时间：
2013
影响因子：
3.2
通讯作者：
Tyler,KennethL
中科院分区：
文献类型：
--
作者：
Tyler,KennethL
It was 55 years ago that Richardson Jr. et al. first described the disease they named progressive multifocal leukoencephalopathy (PML)(Astrom et al. 1958). The emergence of the HIV epidemic catapulted this once rare disease to prominence. The introduction of highly active antiretroviral therapy (HAART) has resulted in a 60–75% reduction in the incidence of PML (to~ 0.6–1.3 cases/1,000 person years of HIV)(Engsig et al. 2009; Khanna et al. 2009); although HIV infection still accounts for~ 85% of all PML cases (Brew et al. 2010). In 2005, the first cases of PML associated with biological immunomodulatory therapy were reported, initially with natalizumab and subsequently, in association with other agents including efalizumab, rituximab, and alemtuzumab (reviewed in Major 2010). There have now been (as of 6 May, 2013) 359 reported cases of natalizumab-associated PML among approximately 115,365 treated patients (as of 31March, 2013), with the risk ranging from< 0.1/1,000 in JC virus (JCV) seronegative individuals to 11.2/1,000 in JCV seropositive individuals with prior immunosuppressive therapy who have received more than 24 months of natalizumab treatment.(https://medinfo. biogenidec. com 20 June 2013). Although isolation of the JC polyomavirus and its identification as the causal agent of PML was reported in 1971 (Padgett et al. 1971), the first use of antiviral therapy in PML was not until 1974 with cytarabine (Ara-C)(Conomy et al. 1974). This agent was later shown to be ineffective in an openlabel randomized multicenter clinical trial in HIV-PML which compared antiretroviral therapy combined with intravenous or intrathecal Ara-C to antiretroviral therapy alone (Hall et al. 1998). Another nucleoside analog, cidofovir, was first tested in PML in 1998 (Taoufik et al. 1998). Although a randomized controlled clinical trial of cidofovir in PML has not been performed, a meta-analysis reviewing outcomes from one prospective and five cohort studies failed to identify a survival benefit in HIV-PML (De Luca et al. 2008). One nonrandomized and uncontrolled open-label observational study suggested that interferon-alpha could delay progression, reduce symptoms, and prolong survival in HIV-PML (Huang et al. 1998), although a more recent retrospective analysis failed to demonstrate any benefit of interferon-alpha treatment beyond that conferred by HAART alone in HIV-PML (Geschwind et al. 2001). Topotecan, a semisynthetic analog of camptothecan and a topoisomerase inhibitor, was evaluated in a small (11 subject) uncontrolled and un-blinded trial in HIV-PML (Royal et al. 2003). Although 3 of the 11 evaluable patients responded to therapy, the lack of controls and the small sample size precludes any meaningful conclusions, and moderately severe or severe neutropenia, anemia, and thrombocytopenia was seen in 42–83% of those treated. Other agents tested in PML in mostly anecdotal reports have included interleukin-2 (IL-2) and 5-HT2-receptor antagonists. Enthusiasm for the testing of 5-HT2 antagonists, which include mirtazapine and risperidone, was engendered by initial reports suggesting that the 5-HT2a serotonin receptor could serve as a JCV receptor (Elphick et al. 2004). Subsequent studies suggest that although the 5-HT2 receptor may play a role in JCV cell entry, it is not a JCV cell surface receptor and that the virus, instead, binds to sialylated oligosaccharides that contain a specific pentasaccharide motif (“LsTc”) on host glycoproteins (Neu et al. 2010). No controlled trials of 5-HT2 antagonists in PML have been performed, although no noticeable effect on survival was noted in one prospective study of determinants of survival in PML …
