Test can predict non-Hodgkin's lymphoma in people with HIV

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The risk of non-Hodgkin’s lymphoma developing in people with HIV within two to five years can be predicted with a high degree of accuracy using an assay already used to monitor for the development of multiple myeloma, according to findings presented on Monday at the Sixteenth Conference on Retroviruses and Opportunistic Infections in Montreal, Canada.

Non-Hodgkin’s lymphoma is a relatively common cancer in people with HIV, and the most common type of lymphoma seen in people with HIV. It is a tumour that involves the uncontrolled multiplication of a type of white blood cells called lymphocytes. The vast majority of non-Hodgkin’s lymphomas are B-cell lymphomas, which are a result of uncontrolled proliferation of B-lymphocytes, the antibody-generating group of lymphocytes.

A range of cancers are related to B-cell proliferation, and a variety of markers of proliferation have been proposed as potential monitoring tools for predicting the development of these types of cancers.

Glossary

non-Hodgkin lymphoma

A group of lymphomas (cancers of the lymphatic system). The many types of non-Hodgkin lymphoma (NHL) are classified according to how fast the cancer spreads. Although the symptoms of NHLs vary, they often include swollen lymph nodes, fever, and weight loss. Certain types of NHLs, such as Burkitt lymphoma and immunoblastic lymphoma, are AIDS-defining cancers in people with HIV.

lymphoma

A type of cancer that starts in the tissues of the lymphatic system, including the lymph nodes, spleen, and bone marrow. In people who have HIV, certain lymphomas, such as Burkitt lymphoma, are AIDS-defining conditions.

proliferation

Multiplication (e.g. of immune system cells) to control an infection.

immunoglobulin

Another name for antibodies. An antibody is a protein substance produced by the immune system in response to a foreign organism (such as bacteria, virus or parasite).

case-control study

An observational study in which a group of people with an infection or condition (called ‘cases’) are compared with a group of people without the infection or condition (called ‘controls’). The past events and behaviour of the two groups are compared. Case-control studies can help us understand the risk factors for having an infection or a condition. However, it is difficult both to accurately collect information about past events and to eliminate bias from case-control studies.

Multiple myeloma, a cancer that emerges in the plasma cells of the bone marrow, is already routinely monitored using a free light chain assay. A light chain is a molecule that is normally bound to an immunoglobulin, or antibody, produced by B-cells. In the presence of myeloma, levels of unlinked, or free, light chain levels are elevated.

Researchers from the US National Cancer Institute and the Mayo Clinic in Rochester, New York, conducted a case-control study that matched 66 HIV-positive cases of non-Hodgkin’s lymphoma occurring between 1985 and 2004, each with four HIV-positive control cases selected on the basis of matching sex, race, age and CD4 count (225 total controls).

Levels of immunoglobulin (Ig) G, IgM and IgA levels were measured from stored plasma samples, together with levels of kappa and lambda free light chains, and their predictive value for the development of NHL was assessed.

Levels of kappa and lambda free light chains were found to strongly predict the development of NHL two to five years in advance, and levels of these molecules were elevated in all HIV-positive individuals compared with reference levels in the general population. The kappa/lamda free light chain ratio did not predict NHL, and nor did changes in free light chain levels over time.

Immunoglobulin levels did not predict the development of NHL.

However applicability of the findings may be limited by the lack of antiretroviral therapy; Eric Engels of the National Cancer Institute said that only 10% of those diagnosed with NHL had been taking antiretroviral drugs prior to the development of the tumour, and the median CD4 count at diagnosis was 74 cells/mm3. The median year of diagnosis was 1994.

Nevertheless, said Engels, the monitoring of free light chains could help to identify patients who need to start antiretroviral treatment early in order to reduce the risk of developing NHL, or to detect relapse of NHL after treatment.

References

Landgren O et al. Risk of AIDS non-Hodgkin’s lymphoma is strongly predicted by elevated levels of circulating immunoglobulin-free light chains. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 29, 2009.