Lymphoma in Patients With HIV Infection
NHL is an AIDS-defining diagnosis. After active antiretroviral therapy (HAART) became widely available, the incidence of NHL in developed countries decreased dramatically in HIV-infected patients. However, it occurs 20 to 50 times more often in HIV-infected patients than in non-HIV-infected patients. B-cell lymphomas predominate in HIV-infected patients, with the most common types being DLBCL, Burkitt lymphoma, and Burkitt-like lymphoma. Treatment outcomes for HIVrelated NHL in patients on HAART have improved substantially and are now similar to outcomes for patients without HIV infection.
Autologous Transplantation
Auto-HCT in patients with AIDS and lymphoma was initially presented in case reports and small series. One study reported on 20 patients with relapsed, inductionfailure, or high-risk lymphoma (18 patients with NHL and 2 patients with Hodgkin disease) using conditioning therapy with cyclophosphamide, etoposide, and carmustine or TBI. At a median length of follow-up of 31.8 months, 17 of the 20 patients were free of disease, 1 died of transplant-related complications, and 2 died of relapsed lymphoma early following transplant. The AIDS Malignancy Consortium published the results of autologous transplant in high-risk HIV-associated lymphoma in 15 patients with NHL and 5 patients with Hodgkin disease using low-dose busulfan and cyclophosphamide as conditioning. Of the 20 patients, 10 were alive and event-free at a median of 23 weeks following autologous transplant.
The EBMT Lymphoma Working Party presented the results of a retrospective analysis on treatment outcomes of 68 patients with HIV lymphoma who underwent auto- HCT using predominantly BEAM conditioning (n = 65). The cumulative incidence of nonrelapse mortality was 7.5% at 12 months, mainly from bacterial infections. The cumulative incidence of relapse was 30.4% at 24 months. At a median follow-up of 32 months, PFS and OS rates were 56%. Status of disease at transplantation and chemotherapy sensitivity correlated well with outcomes.
Two recent case-control studies compared the survival of HIV-infected patients and uninfected patients undergoing auto-HCT for lymphoma and found similar outcomes. Taken together, these results confirm that auto-HCT in patients with lymphoma and HIV infection is feasible, safe, and effective. In most studies, the patients continued HAART therapy throughout the peritransplant period. Survival, relapse, and nonrelapse mortality were similar to those seen in patients without HIV infection; however, no formal comparative studies have been done. The BMT CTN is currently enrolling patients on a phase II multicenter trial (CTN 0803) using BEAM as the conditioning regimen followed by auto-HCT for chemotherapy-sensitive aggressive B-celllymphoma and Hodgkin lymphoma in patients with HIV infection. In addition to lymphoma and transplantrelated outcomes, this trial will assess HIV biology, HIV lymphoma tumor markers, and other correlative studies.
In summary, auto-HCT in patients with well-controlled HIV infection has similar outcomes compared with patients without HIV infection. Therefore, HIV infection should not be a contraindication for auto-HCT. The indications for transplant are similar in HIV-positive or HIV-negative patients with lymphoma.
Allogeneic Transplantation
Before HAART was available, initial attempts to treat HIV-infected patients with allo-HCT led to extremely poor outcomes. After HAART became widely available, several case reports suggested a potential benefit of allo-HCT in this patient population. Allo-HCT in patients with malignancy and HIV infection has particular challenges, including the risk of opportunistic infection before and after transplantation, the high frequency of other concomitant viral infections, the potential impact of HIV in bone marrow environment and immune reconstitution posttransplant, and the potential for complex interactions between HAART, high-dose therapy, and immunosuppressive agents.
The CIBMTR retrospectively evaluated the results of allo-HCT in 23 HIV-infected patients undergoing transplant between 1987 and 2003, including patients receiving transplantation prior to the advent of HAART. Median age at transplant was 32 years. The indications for transplant included primarily malignant conditions, with lymphoma being the most common, followed by acute leukemia. Bone marrow was the graft in most patients, and the common donor sources were HLA-identical siblings. Median time to neutrophil engraftment was 16 days, cumulative incidence of grade II to IV acute GVHD was 30%, and cumulative incidence of chronic GVHD at 2 years was 28%. With a median follow-up of 6 months, 30% of the patients were alive at 2 years; the primary causes of death were organ toxicity and infection. Despite initial mortality due to organ damage and infection, several patients achieved long-lasting remission. With currently available therapy, development of AIDS can be prolonged for decades with minimal morbidity; therefore, HIV infection should not be considered a contraindication for allo-HCT. Prospective studies with modern HAART and transplant support are needed. The BMT CTN is conducting a prospective multicenter trial (CTN 0903) enrolling patients with HIV infection and malignancy or bone marrow failure to assess the day 100 mortality after allo-HSCT. This trial will also study OS, PFS, and the impact of HCT on HIV reservoirs.