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. 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 human immunodeficiency virus (HIV) infection makes the use of immunosuppressive chemotherapy difficult.
A large number of retrospective studies and several prospective studies have been reported using regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD), and infusional cyclophosphamide, doxorubicin, and etoposide.[1-4] The patients who go into remission are more likely to have less disease, no bone marrow or CNS involvement, no prior AIDS-defining illness, and a better performance status. Patients at risk for subsequent CNS involvement include those with bone marrow involvement or those with Epstein-Barr virus identified in the primary tumor or in the cerebrospinal fluid (i.e., by polymerase chain reaction).[5-7] Intrathecal chemotherapy is usually considered for those patients at higher risk for CNS involvement.
Prior to the highly active antiretroviral therapy (HAART) era, a randomized trial of patients with HIV and either Burkitt lymphoma (BL) or diffuse large B-cell lymphoma (DLBCL) compared standard dose chemotherapy and growth factor support with reduced-dose chemotherapy. No difference was found in overall survival (OS) between the two dose levels, and no difference was observed between the historic groups (BL and DLBCL); however, the median survival was equally poor at 6 to 7 months.[Level of evidence: 1iiA] The introduction of HAART has led to a marked reduction in opportunistic infections, prolonged survival with HIV infection, and a median OS for patients with AIDS-related lymphoma, which is comparable to the outcome in the nonimmunosuppressed population.[4,8-14][Level of evidence: 3iiiDiv] The use of HAART has also allowed the use of standard dose and even intensive chemotherapy regimens to be given with reasonable safety to patients with AIDS-related lymphomas, which is comparable to the outcome in non-HIV patients.[3,4,13-16]
In a retrospective review of 363 patients with HIV-associated lymphoma, survival of patients with HIV-DLBCL improved in the HAART era, but survival of similarly treated patients with HIV-BL remained poor.[Level of evidence: 3iiiDiv] Future studies will evaluate if more intensive chemotherapy appropriate for non-HIV patients with BL results in better outcomes for patients with HIV-BL. A prospective randomized comparison (AMC-010) of rituximab plus CHOP (R-CHOP) versus CHOP in 150 patients with HIV-DLBCL and HIV-BL showed no difference in (OS); treatment-related infectious deaths occurred in 14% of patients who received R-CHOP versus 2% of patients who received CHOP alone (P = .035).[Level of evidence: 1iiA] A Cochrane meta-analysis published in 2009 evaluated 857 patients in four randomized clinical trials; no clinical conclusions regarding the optimal regimen could be reached as a result of varying interventions and the lack of adequately powered trials with a low risk of bias.
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 transplantation. Long-term survivors have been reported anecdotally for these highly selected patients who relapsed.[20-23][Level of evidence: 3iiiDiv]Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with AIDS-related peripheral/systemic lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
- Kaplan LD, Straus DJ, Testa MA, et al.: Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 336 (23): 1641-8, 1997. [PUBMED Abstract]
- Sparano JA, Lee S, Chen MG, et al.: Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Trial (E1494). J Clin Oncol 22 (8): 1491-500, 2004. [PUBMED Abstract]
- Ratner L, Lee J, Tang S, et al.: Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol 19 (8): 2171-8, 2001. [PUBMED Abstract]
- Levine AM, Tulpule A, Espina B, et al.: Liposome-encapsulated doxorubicin in combination with standard agents (cyclophosphamide, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma: results of therapy and correlates of response. J Clin Oncol 22 (13): 2662-70, 2004. [PUBMED Abstract]
- Gill PS, Levine AM, Krailo M, et al.: AIDS-related malignant lymphoma: results of prospective treatment trials. J Clin Oncol 5 (9): 1322-8, 1987. [PUBMED Abstract]
- Cingolani A, Gastaldi R, Fassone L, et al.: Epstein-Barr virus infection is predictive of CNS involvement in systemic AIDS-related non-Hodgkin's lymphomas. J Clin Oncol 18 (19): 3325-30, 2000. [PUBMED Abstract]
- Scadden DT: Epstein-Barr virus, the CNS, and AIDS-related lymphomas: as close as flame to smoke. J Clin Oncol 18 (19): 3323-4, 2000. [PUBMED Abstract]
- Palella FJ Jr, Delaney KM, Moorman AC, et al.: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338 (13): 853-60, 1998. [PUBMED Abstract]
- Antinori A, Cingolani A, Alba L, et al.: Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy. AIDS 15 (12): 1483-91, 2001. [PUBMED Abstract]
- Hoffmann C, Wolf E, Fätkenheuer G, et al.: Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma. AIDS 17 (10): 1521-9, 2003. [PUBMED Abstract]
- Tam HK, Zhang ZF, Jacobson LP, et al.: Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer 98 (6): 916-22, 2002. [PUBMED Abstract]
- Vaccher E, Spina M, Talamini R, et al.: Improvement of systemic human immunodeficiency virus-related non-Hodgkin lymphoma outcome in the era of highly active antiretroviral therapy. Clin Infect Dis 37 (11): 1556-64, 2003. [PUBMED Abstract]
- Mounier N, Spina M, Gabarre J, et al.: AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy. Blood 107 (10): 3832-40, 2006. [PUBMED Abstract]
- Weiss R, Mitrou P, Arasteh K, et al.: Acquired immunodeficiency syndrome-related lymphoma: simultaneous treatment with combined cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy and highly active antiretroviral therapy is safe and improves survival--results of the German Multicenter Trial. Cancer 106 (7): 1560-8, 2006. [PUBMED Abstract]
- Wang ES, Straus DJ, Teruya-Feldstein J, et al.: Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer 98 (6): 1196-205, 2003. [PUBMED Abstract]
- Cortes J, Thomas D, Rios A, et al.: Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Cancer 94 (5): 1492-9, 2002. [PUBMED Abstract]
- Lim ST, Karim R, Nathwani BN, et al.: AIDS-related Burkitt's lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy. J Clin Oncol 23 (19): 4430-8, 2005. [PUBMED Abstract]
- Kaplan LD, Lee JY, Ambinder RF, et al.: Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood 106 (5): 1538-43, 2005. [PUBMED Abstract]
- Martí-Carvajal AJ, Cardona AF, Lawrence A: Interventions for previously untreated patients with AIDS-associated non-Hodgkin's lymphoma. Cochrane Database Syst Rev (3): CD005419, 2009. [PUBMED Abstract]
- Re A, Michieli M, Casari S, et al.: High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for AIDS-related lymphoma: long-term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors. Blood 114 (7): 1306-13, 2009. [PUBMED Abstract]
- Krishnan A, Molina A, Zaia J, et al.: Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 105 (2): 874-8, 2005. [PUBMED Abstract]
- Costello RT, Zerazhi H, Charbonnier A, et al.: Intensive sequential chemotherapy with hematopoietic growth factor support for non-Hodgkin lymphoma in patients infected with the human immunodeficiency virus. Cancer 100 (4): 667-76, 2004. [PUBMED Abstract]
- Balsalobre P, Díez-Martín JL, Re A, et al.: Autologous stem-cell transplantation in patients with HIV-related lymphoma. J Clin Oncol 27 (13): 2192-8, 2009. [PUBMED Abstract]