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HIV-Associated Lymphoma

HIV-associated, non-Hodgkin’s lymphoma occurs in 5-10% of individuals with HIV infection. The incidence of lymphoma in this population has been rising and may reflect prolonged survival related to the use of highly-active antiretroviral therapy and

Pathophysiology

HIV-associated non-Hodgkin's lymphomas are virtually all of B-cell origin. Most are intermediate- or high-grade lymphomas categorized as large cell (60%) or small non-cleaved  lymphomas (25%).

Seventy-five percent of patients with systemic lymphoma have a lymphoma, HIV-lymphoma, limphoma, lympoma³. Most present with extranodal disease, often in the bone marrow, meninges, liver or

Comparison of Molecular and Clinical Features of AIDS-lymphomas
	Systemic	CNS	Primary Effusion
Histology	Large Cell (60%) Small noncleaved (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 33-62% of patients. Relapse occurs in 25% of complete responders within 6 months. Median survival is 4-8 months, with about half dying of lymphoma and half of opportunistic infection. Median survivals as long as 18 months have

Low-dose mBACOD is associated with a similar response and survival as

Low-dose mBACOD
Agent	Dose	Days
Cyclophosphamide	300 mg/m2, IV	1
Doxorubicin	25 mg/m2, IV	1
Bleomycin	4 mg/m2, IV	1
Vincristine	2 mg, IV	1
Dexamethasone	3 mg/m2, po	1-5
Methotrexate	500 mg/m2, IV Folinic acid rescue 25 mg q 6h x 6 beginning 24hours after completion of MTX	15

Aggressive chemotherapy is associated with a higher risk of death due to opportunistic infection Myeloid growth factors (G-CSF, GM-CSF) have been shown to reduce hematologic toxicity in patients receiving standard-dose chemotherapy. Myeloid growth factors are usually not needed in patients receiving a reduced-dose treatment regimen.

Meningeal prophylaxis with intrathecal MTX or cytosine arabinoside is indicated for patients with a positive bone marrow biopsy, small noncleaved histology, paranasal or epidural involvement, and for advanced stage IV disease. The dosage of intrathecal cytosine arabinoside is 50 mg in 6 cc preservative-free saline, weekly, during the

Treatment recommendations: Systemic non-Hodgkin’s lymphoma

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

CD4 >100/mm³: Consider standard-dose chemotherapy in selected patients.

Antibiotic prophylaxis for P. carinii in all patients.

Meningeal prophylaxis for those with small noncleaved histology, bone marrow involvement, paranasal sinus involvement, or epidural disease.

Antiviral therapy:

Combination antiviral therapy should be continued with chemotherapy

Zidovudine is not recommended due to risk of overlapping myelosuppression.

Primary central nervous system lymphoma in HIV infection

These individuals present with severe immunodeficiency, most with CD4 lymphocyte counts <50/mm³. Antitoxoplasma therapy is appropriate only in those individuals who are toxoplasma seropositive. Patients who are seronegative should undergo brain biopsy to rule out the presence of lymphoma.

Solitary lesions are more likely to be lymphoma.

Up to 20% have a positive CSF cytology. A lumbar puncture should be performed if not contraindicated.

Thallium-SPECT is usually positive in lymphoma, and it is usually negative in toxoplasmosis.

PCR for EBV in CSF: 80-85% sensitive, 90% specific for lymphoma. PCR testing may reduce the need for invasive diagnosis.

Treatment consists of whole brain radiotherapy. Three quarters of these individuals will have a clinical responses to therapy (improvement in neurologic symptoms). The median survival is only 2-4 months, and most deaths are