HIV infection increases cancer risk and is linked to cancers associated to infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. Lymphomas represent one of the most frequent malignancies among individuals infected by HIV. Diffuse large B-cell lymphoma remains a leading cancer after the introduction of combined antiretroviral therapy (cART). The incidence of other lymphomas including Burkitt lymphoma, primary effusion lymphomas, and plasmablastic lymphoma of the oral cavity remain stable, whereas the incidence of Hodgkin lymphoma and Kaposi sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman disease has increased. The heterogeneity of lymphomas in individuals infected by HIV likely depends on the complexity of involved pathogenetic mechanisms (ie, HIV-induced immunosuppression, genetic abnormalities, cytokine dysregulation, and coinfection with the gammaherpesviruses Epstein-Barr virus and KSHV) and the dysregulation of the immune responses controlling these viruses. In the modern cART era, standard treatments for HIV-associated lymphoma including stem cell transplantation in relapsed/refractory disease mirror that of the general population. The combination of cART and antineoplastic treatments has resulted in remarkable prolongation of long-term survival. However, oncolytic and immunotherapic strategies and therapies targeting specific viral oncogenes will need to be developed.

After the introduction of highly active antiretroviral therapy (HAART), intensive treatment, including high-dose therapy (HDT) and peripheral blood stem cell transplantation (PBSCT), has become feasible in HIV-positive patients with Hodgkin (HL) and non-Hodgkin (NHL) lymphoma. Herein, we report the long-term results, on an intention-to-treat basis, of a prospective study on HDT and PBSCT in 50 HIV-positive HAART-responding patients with refractory/relapsed lymphoma. After debulking therapy, 2 patients had early toxic deaths, 10 had chemoresistant disease, 6 failed stem cell mobilization, 1 refused collection, and 4 progressed soon after PBSC harvest. Twenty-seven actually received transplant. Twenty-one patients are alive and disease-free after a median follow-up of 44 months (OS, 74.6%; PFS, 75.9%). Only lymphoma response significantly affected OS after transplantation. In multivariate analyses both lymphoma stage and low CD4 count negatively influenced the possibility to receive transplant. Median OS of all 50 eligible patients was 33 months (OS, 49.8%; PFS, 48.9%). Low CD4 count, marrow involvement, and poor performance status independently affected survival. PBSCT is a highly effective salvage treatment for chemosensitive AIDS-related lymphoma. It seems rational to explore its use earlier during the course of lymphoma to increase the proportion of patients who can actually receive transplant.

Background Effort-induced myocardial ischemia (EMI) has been seldom described. Aims of our study were (A) to evaluate the prevalence of EMI during long-lasting 5-FU infusion; (B) to identify possible risk factors of EMI during 5-FU infusion. Patients and methods For the purpose (A), we prospectively evaluated a group of patients undergoing in-hospital continuous infusion (c.i.) of 5-FU. Patients with rest ischemia were excluded. Among 358 consecutive patients, 21 (5.9%) had rest ischemia; 109 could not perform a stress test. The remaining 228 patients underwent a treadmill stress test (TST) after >46 h of 5-FU infusion. For the purpose (B), we compared the characteristics of patients with EMI (including 3 previously described in a 2001 paper) with those without EMI. Results Among 228 patients, 16 (6.9%) had EMI. These 16 had a second TST after stopping 5-FU: in 14, it was negative, 2 patients with coronary artery disease had milder ischemia. The whole group of 231 (including 3 described in a previous paper) patients undergoing TST included 148 males and 83 females, with mean age of 57.5. Cardiovascular risk factors were present in 178 of them. Eight patients had ischemic heart disease. Among 19 patients with EMI, 7 had angina, 12 silent ischemia. ST segment at ECG was elevated in 10 patients, depressed in 9. Comparing the group with toxicity and the one without, the only significant difference was the complaint of atypical symptoms at rest before the TST. No difference was observed as regards: chemotherapy schedule (chronic c.i. in 49, 5 days in 178, FOLFOX type in 12), coronary risk factors or heart disease. Conclusions EMI is as frequent as rest ischemia during 5-FU infusion. Patients undergoing 5-FU continuous infusions should be adviced to avoid unusual efforts, to refer any cardiac symptom, and should be investigated for EMI.

In the HAART era Kaposis sarcoma (KS) remains the second most frequent tumor in HIV-infected patients worldwide, and it has become the most common cancer in Sub-Saharan Africa. In western countries the risk for KS in men having sex with men (MSM) is 5 to 10 times higher compared to other groups of individuals practicing other HIVrisk behaviors. Patients with KS in Sub-Saharan Africa have very high tumor burdens and rapid disease progression with a diminished life expectancy of less than 6 months. KS lesions are comprised of both distinctive spindle cells of endothelial origin and a variable inflammatory infiltrate, which suggests that KS may result from reactive hyperproliferation induced by chronic inflammation, and therefore it is not a true neoplasm. KS has a variable clinical course ranging from very indolent forms, requiring no or minimal therapy, to a rapidly progressive disease. Treatment decisions must take into consideration the extent and the rate of tumor growth, patients symptoms, immune system conditions and concurrent HIV-related complications. Several different therapeutic options are available but the optimal therapy is still unclear. Highly Active Antiretroviral Therapy (HAART) including protease inhibitors (PI) may represent the first treatment step for slowly progressive disease; chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease, whereas maintenance (M)-HAART after systemic chemotherapy may be an effective anti-KS measure after debulking CT. The angiogenic nature of KS makes it particularly suitable for therapies based on targeted agents such as metalloproteinase inhibitors, angiogenesis inhibitors and tyrosine kinase inhibitors. The aim of this article is to provide an up-to-date review of the current status and perspectives of AIDS-related KS in the HAART era.