Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: Impact of novel therapies

Abstract

The aims of this study were to evaluate the clinical characteristics of HIV-negative patients affected by lymphoproliferative disorders (LPD) who developed progressive multifocal leukoencephalopathy (PML), to delineate the risk factors, and to analyze whether the new antineoplastic therapies are changing the natural history of this infectious disease. We retrospectively analyzed 46 cases with confirmed LPD-associated PML published from 1958 to 2004. Patients were stratified according to two different time periods: group A included patients diagnosed before 1989, and group B included patients diagnosed since 1990, after introduction of purine analogues. Group A patients (n = 22) had received alkylating agents and/or radiotherapy, and the majority (63.6%) had advanced Hodgkin disease. At univariate analysis, uncontrolled Hodgkin disease was the only risk factor for PML. In group B patients (n = 24), the most frequent treatments received were purine analogues (58.3%) and high-dose therapy with hematopoietic stem cell transplantation (33.3%; HDT/HSCT). B-cell chronic lymphocytic leukemia (45.8%) and aggressive non-Hodgkin lymphoma (24.9%) were the most frequent underlying LPDs. Patients treated with purine analogues were more likely to have active LPD, lower CD4 cell counts, and to be older and male than were HSCT recipients. The median interval from purine analogues or HDT/HSCT to PML was 11 months. In HDT/HSCT recipients, this interval was delayed for 10 months when peri-transplantation rituximab was used. Univariate analysis identified age >55 years, male sex, and CD4 cell counts £0.2 · 10 9 /L as risk factors for PML in patients treated with purine analogues. Mortality rates were 95.4% (group A patients), 90% (purine analogues), and 62.5% (HDT/HSCT recipients). At univariate analysis, the only factor that significantly correlated with recovery from infection was female sex. Our findings indicate (1) the possible reduction in reported cases associated with Hodgkin disease and the increasing number of published cases associated with the new antineoplastic therapies (purine analogues and HDT/ HSCT); (2) among patients treated with purine analogues, PML is more common in male patients with CD4 cell counts £0.2 · 10 9 /L; (3) the use of rituximab after HDT/ HSCT seems to delay the onset of PML; and (4) the prognosis is slightly better in transplant recipients. Am.

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

“…Despite the use of highly active antiretroviral therapy (HAART) for HIV, HIV infection is still by far the leading cause of PML, accounting for Ͼ80% of cases (56,58). In non-rheumatic disease immunosuppressed states, such as malignancies and organ transplantation, most cases of PML occur with combination chemotherapy, especially with purine antagonists and high-dose immunosuppression, as well as with hematopoietic stem cell transplantation (59). Occasional patients treated with single-agent immunosuppression regimens, including corticosteroids alone (59,(60)(61)(62)(63)(64)(65), have also developed PML.…”

“…In non-rheumatic disease immunosuppressed states, such as malignancies and organ transplantation, most cases of PML occur with combination chemotherapy, especially with purine antagonists and high-dose immunosuppression, as well as with hematopoietic stem cell transplantation (59). Occasional patients treated with single-agent immunosuppression regimens, including corticosteroids alone (59,(60)(61)(62)(63)(64)(65), have also developed PML. Recently, PML has been reported to occur in patients receiving natalizumab (33,66,67) and rituximab (68).…”

Progressive Multifocal Leukoencephalopathy during Ixazomib-Based Chemotherapy

“…One study estimated the one-year survival for hiv-negative patients to be 58% 17 . Another study found patients with a hematological malignancy who developed pml had a 12% survival at 10 months 18 . In the ms population, a number of poor prognostic risk factors have been identified 16 .…”

Progressive Multifocal Leukoencephalopathy in Chronic Lymphocytic Leukemia: Case Report and Review of the Literature

“…Özellikle lenforetiküler dokularda, böbrek ve beyinde latent olarak bulunur ve immünsüpresyon ile reaktivasyon durumunda PML'ye neden olur. [3][4][5][6] PML en çok oksipital ve frontal serebral beyaz cevheri etkiler. Serebellar ve beyin sapı tutulumu bu lokalizasyonları takip eder.…”

“…En sık ikinci neden, kronik lenfositik lösemi (KLL), non-Hodgkin, Hodgkin lenfoma gibi lenforetiküler malignansilerdir. 3,4 Hematolojik malignansiler içinde KLL hastaları da sıklıkla bildirilmiştir. KLL hastalarında %0,53 oranında PML geliştiği rapor edilmiştir.…”