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HIV-Associated Lymphoma

 Epidemiology

ß-cell lymphoma occurs in between 5 and 10% of individuals with HIV infection. The incidence of lymphoma in this population has been rising.

Etiology

Etiology is unknown. Unlike transplant-associated NHL, Epstein-Barr virus has not been shown to be associated with a majority of systemic lymphomas. However, EBV DNA is found in 100% of primary CNS  lymphomas.

Other similarities exist with transplant-associated NHL. Polyclonal lymphomas have been identified.

In vitro evidence suggests a role for interleukins 6 and 10 in pathogenesis. Inhibition of these cytokines results in growth inhibition in lymphoma.

Body-cavity based lymphomas associated with HHV-8.

Pathology

HIV-associated non-Hodgkin's lymphomas are virtually all of B-cell origin. Most are intermediate- or high-grade lymphomas categorized as

 

	Systemic	CNS	Primary Effusion
Histology	Large Cell (60%) SNC (30%)	Large Cell	Pleomorphic large cell
Clonality	Monoclonal polyclonal	Monoclonal	Monoclonal
EBV	Present in minority	Always present	Often present
HIV- 8	Absent	Absent	Present
Median CD4+	100	30	90
Survival (median)	6-8 months	3 months	5 months

Treatment

Complete response occurs in

Relapse occurs in approximately 25% of complete responders.

Reported median survival 4-8 months with about half dying of lymphoma and half of opportunistic infection.

Recently identified poor prognostic categories age >35 or 40.

Approaches to therapy that have been used include reduced-dose chemotherapeutic regimens (low-dose mBACOD or CHOP) and the use

Low-dose mBACOD: In a non-randomized clinical trial this treatment regimen is associated with similar response and survival as has been observed with more standard treatment regimens but at the expense of less myelosuppression.

Meningeal prophylaxis (intrathecal MTX or cytosine arabinoside) clearly indicated for those with positive bone marrow, small noncleaved.

Infusional cyclophosphamide, doxorubicin, etoposide (CDE) (Investigational)

Associated with similar complete response rate as with other regimens (60%)

Long survival reported (median 18 months) in pilot study.

Large phase II trial in progress (ECOG) results appear to be similar.

Treatment recommendations: Systemic NHL

All patients with CD4<100/mm3: low-dose chemotherapy

Novel therapeutic approaches are currently being explored:

Immunotoxins: anti-CD20, anti-CD 22, anti-CD 19

Inhibitors of IL-6:IL-4 3. interleukin-2 (IL-2)

High-dose zidovudine with interferon and gancyclovir

Agents targeting proliferating macrophages

Primary central nervous system lymphoma in HIV infection

These individuals present with severe immunodeficiency, most with CD4 lymphocyte counts< 50/mm^{3. Early diagnosis is important for patients with enhancing intercerebral lesions.}

^{Anti-toxoplasma therapy is appropriate only in those individuals who are toxoplasma seropositive. Patients who are seronegative should undergo early brain biopsy to rule out the presence of lymphoma.}

^{1.    Radiographic appearance not diagnostic. However, solitary lesion more likely to be lymphoma.}

^{2.    Up to 20% have positive CSF cytology -- LP should be performed if not contraindicated.}

^{3.    Thallium -- SPECT: usually positive in lymphoma negative in toxo.}

^{4.    PCR for EBV in CSF: 80-85% sensitive, 90% specific for lymphoma. Where available may reduce need for invasive diagnosis.}

^{B.    The standard approach to treatment is whole brain radiotherapy. Three quarters of these individuals will have clinical responses to therapy (improvement in neurologic symtoms). Median survival only 2-4 months. Most deaths are due to opportunistic infection. There is no evidence that more aggressive approaches to treatment are more effective at this time.}

^{C.    Radiation combined with chemotherapy associated with better response rate but without survival belle}      

^{D.    Isolated reports of tumor regression with antiretroviral therapy alone.}

^{Anogenital Neoplasia}

A.    C(A) IN = Cervical (Anal) Intraepithelial neoplasia

^{B.     SIL = Squamous intraepithelial lesion}

^{C.    ASCUS = Atypical squamous cells of undetermined significance}

^{D.    CIN1 (mild dysplasia) - LSIL}

^{E.    CIN2 (moderate dysplasia) - HSIL}

^{F.    CIN3 (severe dysplasia) - HSIL}

^{II.    Cervical intraepithelial neoplasia (CIN) and invasive squamous carcinoma.}

A.    Incidence of invasive disease not clearly increased.

Anogenital Neoplasia