Treatment Of HIV-associated Lymphoma Research Articles

Progress in the Treatment of HIV-Associated Lymphoma When Combined With the Antiretroviral Therapies.

With the wide use of combination antiretroviral therapy (cART), the life expectancy of HIV-infected individuals drastically improved. However, HIV infection and HIV-associated cancers were the most common causes of death in the HIV-infected populations. The HIV-associated cancers are divided into acquired immune deficiency syndrome (AIDS)-defining and non-AIDS-defining cancers based on the incidence among the HIV-infected patients. Among HIV-associated cancers, acquired immune deficiency syndrome-related lymphoma (ARL) is still the most common condition and the leading cause of HIV/AIDS-related deaths. Diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) are the most common subtypes of the ARL. Although Hodgkin’s lymphoma (HL) is not considered as an AIDS-defining cancer, incidence of HL in HIV-infected individuals is higher than the general population. The review summarizes the new progress in the treatment of HIV-associated lymphoma.

Aggressive B-Cell Lymphomas

Aggressive B-cell lymphomas (ABLs) are a group of B-cell malignancies, that is, a relatively common form of cancer across the world. This issue on aggressive B-cell lymphomas compiles 12 exciting manuscripts, most of which are very meticulously performed reviews of the available current literature. Three areas of lymphoma pathology and biology that are leading to a greater understanding of relatively recently defined entities are discussed. These include anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (ALK+ LBCL), and the so-called grey zone lymphomas or lymphomas with intermediate features and the posttransplant lymphoproliferative disorders. ALK+ LBCL are characterised by gene rearrangement involving clathrin and ALK genes (t(2;17)(p23;q23)). Grey zone lymphomas include two unclassifiable B-cell lymphomas, one with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL) and the second with features intermediate between DLBCL and Burkitt lymphoma (BL). The biology of common lymphomas is addressed in two manuscripts. M. Rossi et al. review the current literature on molecular subsets of DLBCL, the distinction between DLBCL and BL, and gene expression characteristics of the grey zone lymphomas. This paper is accompanied by M. Cacciatore et al.'s manuscript that explores the importance of the microenvironment in lymphoma biology. Two of the manuscripts deal with those aspects of endemic BL pathogenesis that have hitherto not been explored in great depth. The paper by S. Mannucci et al. explore the possibility of Euphorbia tirucalli acting as a cofactor in BL. They show that, in lymphoblastoid cell lines, E. tirucalli can modulate the EBV latency genes, result in polysomy for chromosome 8, and cause upregulation of c-MYC. Furthermore, Dr. C. van den Bosch raises question about a possible role for RNA viruses in the pathogenesis of BL. Dr. I. Magrath reviews the evolution of BL treatment in Africa—from cyclophosphamide monotherapy to multiagent combination chemotherapy including central nervous system prophylaxis using combinations of cyclophosphamide, vincristine, prednisone, and methotrexate. He also highlights the benefits of collaboration between resource-rich and resource-poor settings. P. Vishnu and D. M. Aboulafia review how the treatment of HIV-associated lymphomas has evolved since the introduction of highly active antiretroviral therapy (HAART). The use of rituximab, in conjunction with multiagent chemotherapy, and where required high-dose chemotherapy (HDCT) and autologous stem cell rescue (ASCT) have all contributed to the success of treating HIV lymphomas. Treatment of ABL is further reviewed in two paper—one on ASCT in DLBCL and the other on novel therapies by K. Foon et al. To complete the issue, S. Donnou reviews the currently available murine models useful for studying lymphomagenesis, the lymphoma microenvironment, and the efficacy of new therapies. By compiling these paper, we hope to enrich our readers and researchers with respect to these particularly common, yet usually highly treatable aggressive B-cell malignancies. Kikkeri N. Naresh Ian Magrath Martine Raphael Lorenzo Leoncini

Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas

AbstractThe treatment of HIV-associated lymphoma has changed since the widespread use of highly active antiretroviral therapy. HIV-infected individuals can tolerate more intensive chemotherapy, as they have better hematologic reserves and fewer infections. This has led to higher response rates in patients with HIV-associated Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL) treated with chemotherapy in conjunction with antiretroviral therapy. However, for patients with refractory or relapsed disease, salvage chemotherapy still offers little chance of long-term survival. In the non-HIV setting, patients with relapsed Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL) have a better chance of long-term remission with high-dose chemotherapy with autologous stem cell rescue (ASCT) compared with conventional salvage chemotherapy. In a prior report we demonstrated that this approach is well tolerated in patients with underlying immunodeficiency from HIV infection. Furthermore, similar engraftment to the non-HIV setting and low infectious risks have been observed. Herein, we expand upon this early experience with the largest single institution series of 20 patients. With long-term follow-up we demonstrate that ASCT can lead to an 85% progression-free survival, which suggests that this approach may be potentially curative in select patients with relapsed HIV-associated HD or NHL.

Stem cell transplantation and gene therapy for HIV-related lymphomas.

The treatment of patients with HIV-related non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) is less successful than in the non-HIV setting, in part due to the aggressive character of these lymphomas but also due to the underlying HIV infection. High-dose therapy with stem cell transplantation has been used with success in the HIV-negative lymphoma setting for high-risk or relapsed disease. However, for patients with HIV-NHL and HIV-HD, ultimately the chance for long-term lymphoma-free survival also depends on successful control of the HIV infection. Gene therapy approaches may provide the opportunity for this long-term control. Herein, we describe the use of high-dose chemotherapy with stem cell rescue in conjunction with current and future gene therapy approaches for the treatment of HIV-associated lymphomas.