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 infection prophylaxis.
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 CD4 cell count>50/mm3. Most present with extranodal disease, often in the bone marrow, meninges, liver or GI tract.
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Comparison of Molecular and Clinical Features of AIDS-lymphomas |
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| 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 been reported. Order Capoten only for: $0.98
| 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.
| CHOP chemotherapy | ||
| Agent | Dose | Day |
| Cyclophosphamide | 750 mg/m2, IV | 1 |
| Doxorubicin | 40 mg/m2, IV | 1 |
| Vincristine | 2 mg | 1 |
| Prednisone | 100 mg, IV | 1-5 |
| G- or GM-CSF | 5 mg/kg/day | 4-13 of each treatment cycle |
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. Buy Zoloft
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. Zelnorm
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 caused by opportunistic infections.