TreatmentUpdate
190

June 2012 

Know your lymphomas

There are several forms of lymphoma that tend to occur among HIV-positive people. Generally speaking, these cancers tend to arise from a type of immune system cell called B-cells. Normally these cells make antibodies that help control certain infections. However, when B-cells are infected with herpes viruses and are over-stimulated by the presence of HIV, they can be set onto a pathway of abnormal development.

Name that lymphoma

Among the lymphomas that can occur among HIV-positive people, relatively common lymphomas are often classed as DLBCL (diffuse large B-cell lymphomas). Lymphomas grouped under DLBCL include the following:

  • primary CNS lymphoma
  • Burkitt lymphoma

The following lymphomas, which are relatively uncommon among HIV-positive people, are also part of the DLBCL grouping:

  • primary effusion lymphoma
  • plasmablastic lymphoma
  • Hodgkin lymphoma

Other uncommon lymphomas in people with HIV include these:

  • follicular lymphoma
  • peripheral T-cell lymphoma

Reducing the risk of cancer with ART

Due to the beneficial effects of ART—the massive reduction in the production of HIV and its proteins, anti-inflammatory activity and improved functioning of the immune system—HIV-related lymphomas are generally less common than they were in time before potent combination therapy for HIV was available. Observational studies have found that taking ART and maintaining a CD4+ count of more than 500 cells helps to reduce the subsequent risk of cancer.

A shift in the type of lymphomas

The general trend across high-income countries toward earlier initiation of ART has meant that low CD4+ cell counts are now less common among HIV-positive people. Lymphomas that were once relatively common among HIV-positive people with severe immune dysfunction—primary CNS lymphoma and primary effusion lymphoma—are less likely today. Instead, Burkitt and Hodgkin lymphomas tend to predominate at the higher CD4+ cell counts that are more common today.

Evaluation of the tumour

The key to determining the type or sub-type of lymphoma present is an analysis of the tumour. This is done in part by examining a sample of the tumour under a microscope and conducting tests on the sample.

Evaluating the person

A person who is diagnosed with cancer will need comprehensive medical history and physical examination as a critical part of their evaluation. Additionally, extensive blood tests and in some cases a biopsy (tissue sample) of the bone marrow may be necessary because lymphoma can affect this part of the body.

A sample of the fluid that bathes the brain and spinal cord—the cerebrospinal fluid (CSF)—may be needed in cases where tumours are aggressive and to be sure that they have not spread to the brain.

CT scans of the body—particularly the chest, abdomen and pelvis—are necessary, as all of these places are rich in lymphatic tissue and have the potential to give rise to tumours. MRI scans may be reserved for the head.

Prognosis

In HIV-negative people with lymphoma a scoring system called the international prognostic index (IPI) is used to help predict the chances of surviving lymphoma. That score takes into account factors such as the following:

  • age (survival is reduced in people over the age of 60)
  • the presence of lymphoma in more than one organ
  • levels of the enzyme lactate dehydrogenase (LDH) in the blood
  • the ability to carry out everyday activities

People who are likely to fare poorly usually have a high score on their IPI (about 4 to 5), while people who are expected to do better tend to have a low score (about zero to 1).

This and other cancer survival scoring systems are controversial in the field of HIV because important factors such as HIV viral load and CD4+ cell counts are not part of the IPI.

Doctors experienced in dealing with HIV-related cancers have found that the following factors generally appear to have an important impact on survival:

  • having a low CD4+ cell count – people with less than 100 CD4+ cells and who have lymphoma tend to be at elevated risk for life-threatening infections and death
  • the location of tumours/cancers in the brain or spinal cord tend to be aggressive and hard to cure

Treatment issues—Antibodies and chemo

Before 1996, survival after a diagnosis of lymphoma was generally poor, averaging about six months. Deaths arose from life-threatening infections, the spread of tumours and possibly the toxicity of chemotherapy.

Today, HIV-positive people diagnosed with cancer tend to have much greater chances of recovery, particularly if the cancers are diagnosed early and if they are also already taking ART. This improved general prognosis is owed primarily to the beneficial effect of ART on the immune system. Another important development that plays a role in survival is the increasing use of the biological therapy rituximab (Rituxan). This is a specially designed antibody that attacks many lymphomas that tend to occur in HIV-positive people. When rituximab is used for treating these lymphomas, recovery rates are relatively high.

Common chemotherapy regimens can include the following:

  • EPOCH – etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin
  • CHOP – cyclophosphamide, doxorubicin, vicristine and prednisone

Different cancer centres use different doses and schedules of these and other regimens.

Chemo and ART

Many drugs used for HIV treatment, particularly protease inhibitors and non-nukes (NNRTIs), have the potential to interact—to raise or lower the level of chemo in the body, and vice versa. This can lead to increased toxicity of chemo drugs, a particular concern for doctors treating cancer because even at normal concentrations chemo is generally associated with side effects.

To avoid or minimize potential interactions, some doctors may choose different courses of action as follows:

  • prescribe chemo and closely monitor the patient for side effects
  • change the prescription of ART (replace protease inhibitors and non-nukes) and use the integrase inhibitor raltegravir (Isentress), which tends to not interact with many other drugs
  • suspend the use of ART for several weeks while a patient is receiving chemo

In two prospective studies where ART was temporarily suspended during administration of chemo, researchers found that CD4+ counts fell and HIV viral loads rose. Importantly, there were no significant increases in serious infections or death. Once ART was reintroduced, viral load and CD4+ counts returned to their pre-interruption levels.

— Sean R. Hosein

REFERENCES:

  1. Navarro WH, Kaplan LD. AIDS-related lymphoproliferative disease. Blood. 2006 Jan 1;107(1):13-20.
  2. Dunleavy K, Wilson WH. How I treat HIV-associated lymphoma. Blood. 2012 Apr 5;119(14):3245-55.