Malignant Lymphomas

 – Christian Hoffmann –

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 general population, HIV infected patients are affected significantly more frequently by all types of lymphoma (see Table 1). Aggressive non-Hodgkin’s lymphomas of B-cell origin are particularly frequent.

The incidence of lymphomas has been markedly reduced by the introduction of antiretroviral therapy. However, there is evidence that this reduction overall was not as impressive as with KS or most opportunistic infections (COHERE 2009, Franceschi 2010). Thus, the relative proportion of lymphoma among all AIDS-associated illnesses is increasing. The decline of the incidence seems to be greater for lymphoma subtypes that mainly occur in severe immunodeficiency (Kirk 2001, Polesel 2008).

In some HIV cohorts, malignant lymphomas have already overtaken KS 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% and 10% of all deaths in HIV patients in 2000 and 2005, respectively (Bonnet 2009). Among the AIDS-related deaths, NHL (28%) was the by far most frequent event (Lewden 2008).

Table 1. Relative risk of different lymphomas in HIV patients in comparison to the normal population (adapted from Goedert 2000)

Malignant NHL total

165

High-grade malignancy NHL

348

Immunoblastic NHL

652

Burkitt’s NHL

261

Not classifiable

580

Primary CNS lymphoma (PCNSL)

> 1,000

Low-grade malignancy NHL

14

Plasmocytoma

5

Hodgkin’s disease 8

 

Malignant lymphomas in HIV-infected patients are also biologically very heterogeneous and differ in several aspects. The frequency and extent of oncogenic mutations or cytokine dysregulation differ, as does the histogenetic origin of the malignant cells (Porcu 2000). In addition, 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 lymphoma (HL) 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. There is now some evidence that some subtypes of malignant lymphoma can be considered as to be “opportunistic” as severe immunodeficiency is required for the development of these entities. For other lymphoma subtypes, chronic B-cell activation, possibly induced by even low HIV viremia, is a prerequisite (Epeldegui 2007, Zoufaly 2009, Regidor 2011).

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). Despite a better prognosis during recent years (see below), HIV-infected patients with NHL continue to endure substantially higher mortality compared with HIV-uninfected patients with NHL (Chao 2010).

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 HD 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 should follow the recommendations for HIV-negative patients.

 

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Filed under 13. Malignant Lymphomas, Part 3 - AIDS, Systemic Non-Hodgkin lymphomas (NHL)

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