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HIV Medicine 2006 825 pages Download PDF, 5.3 MB
Basics
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Introduction
Malignant lymphomas are neoplastic diseases of the lymphatic system that grow rapidly and aggressively, and lead to death within a few weeks or months if left untreated. Hodgkin's disease (HD) is distinguished from the large group of non-Hodgkin's lymphomas (NHL). In comparison to the normal population, HIV patients are affected significantly more frequently by all types of lymphoma (see Table 1). However, aggressive non-Hodgkin's lymphomas of B-cell origin are particularly frequent. The influence of HAART on the incidence of lymphomas is still the subject of controversy. In 2001, several studies indicated that a regression, if any, was by far not as impressive as with Kaposi's sarcoma or most opportunistic infections (Clarke 2001, Little 2001). In a more recent interim analysis (Kirk 2001), however, a moderate regression was demonstrated. This was shown to be particularly true for all the subtypes that mainly occur in severe immunodeficiency (see below). But, in comparison to other malignancies and opportunistic infections, the regression is much smaller, so that the relative proportion of AIDS-associated illnesses that are lymphomas is increasing. In some HIV cohorts, malignant lymphomas have already overtaken Kaposi's sarcoma as the most frequent malignancy. In the EuroSIDA study, the proportion of AIDS-defined illnesses that were malignant lymphomas increased from less than 4 % in 1994 to 16 % in 1998 (Mocroft 2000). In France, lymphomas accounted for 11 % of all deaths in HIV patients in 2000 (Bonnet 2004). In addition, in the HAART era, HIV patients are living much longer, so that the general risk of lymphoma is rising anyway (Stebbing 2004). Therefore, malignant lymphomas will be a significant morbidity and mortality factor in HIV patients in the future. 
Malignant lymphomas in HIV-infected patients are also biologically very heterogenous and differ in several aspects. For example, the association with EBV and other oncogenic viruses such as HHV-8 or SV40 is very variable. The extent of immunodeficiency also varies significantly. Burkitt's lymphoma and Hodgkin's disease frequently occur even when the immune status is good. In contrast, immunoblastic and especially primary CNS lymphoma (PCNSL) are almost always associated with severe immunodeficiency. The frequency and extent of oncogenic mutations or cytokine dysregulation differ, as does the histogenetic origin of the malignant cells (Porcu 2000). However, HIV-associated lymphomas - both NHL and HD - have numerous common clinical features. Characteristics include the usually aggressive growth, diagnosis in the advanced stages with frequent extranodal manifestations, poorer response to treatment, high relapse rates and an overall poor prognosis (Levine 2000). Even in the HAART era, the treatment of malignant lymphoma remains problematic. Although aggressive chemotherapy is possible in many patients with existing immunodeficiency, it is complicated and requires a close cooperation between HIV clinicians and physicians with experience in hematology/oncology. The following discusses systemic NHL, PCNSL and Hodgkin's lymphoma separately. Multicentric Castleman's disease will also be mentioned as a distinct entity, although it is not considered a malignant lymphoma. Low-grade (indolent) NHLs are very rare in HIV patients, and will therefore not be discussed here. As there are no data or even recommendations available, the treatment of such cases in the HAART era should follow the recommendations for HIV-negative patients.
Systemic Non-Hodgkin lymphomas (NHL)
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