Treatment of AIDS-Related Peripheral/Systemic Lymphoma

The treatment of AIDS-related lymphomas involves overcoming several problems. These are all aggressive lymphomas, which by definition are diffuse large cell/immunoblastic lymphoma or small noncleaved cell lymphoma (Burkitt lymphoma). These lymphomas frequently involve the bone marrow and central nervous system (CNS) and, therefore, are usually in an advanced stage. In addition, the immunodeficiency of AIDS and the leukopenia that is commonly seen with HIV infection makes the use of immunosuppressive chemotherapy challenging.

The introduction of highly active antiretroviral therapy (HAART) has led to a marked reduction in opportunistic infections, prolonged survival with HIV infection, and a median overall survival (OS) for patients with AIDS-related lymphoma that is comparable with the outcome in the nonimmunosuppressed population.[1-7][Level of evidence C3] The use of HAART has also allowed standard-dose and even intensive chemotherapy regimens to be given with reasonable safety to patients with AIDS-related lymphomas, which is comparable with the outcome in patients without HIV.[1-10]

Several prospective nonrandomized trials and pooled individual data from 19 prospective trials that included 1,546 patients show that the addition of rituximab to combination chemotherapy improves the complete response rate, progression-free survival, and OS.[3-6][Level of evidence C3] Several other prospective nonrandomized trials and the pooled individual data from the same 1,546 patients also show that infusional EPOCH (infusional etoposide, infusional vincristine, infusional doxorubicin, cyclophosphamide, and prednisone) produced better outcomes than did CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (hazard ratioOS, 0.33; P = .03).[3,6,7][Level of evidence C3] Concurrent use of HAART with the infusional EPOCH regimen is controversial; one group advocated for HAART after completion of chemotherapy,[7] while others allowed concurrent therapy.[6]

For patients with Burkitt lymphoma, dose-modified regimens such as R-CODOX (cyclophosphamide, doxorubicin, vincristine, methotrexate, cytarabine and rituximab)-M/IVAC (ifosfamide, etoposide, and high-dose cytarabine) or R-EPOCH (etoposide, prednisone, vincristine, and doxorubicin in combination with rituximab) have shown good results with concurrent or sequential HAART.[7,11,12]

Patients at risk of subsequent CNS involvement include those with bone marrow involvement or those with EBV identified in the primary tumor or in the cerebrospinal fluid (i.e., by polymerase chain reaction).[13,14] Intrathecal chemotherapy is usually considered for patients who are at higher risk of CNS involvement.

Highly selected patients with resistant or relapsed lymphoma after first-line chemotherapy and with continued responsiveness to HAART underwent second-line chemotherapy followed by high-dose therapy and autologous peripheral stem cell transplant. Long-term survivors have been reported anecdotally for these highly selected patients who relapsed.[15-18][Level of evidence C3]