The seriousness of the problem of pediatric AIDS is increasing; and, judging by the experience of adults with AIDS, there is a high likelihood that there will be increasing numbers of opportunistic lymphomas occurring in these immunodeficient children and adolescents. To address the present dearth of knowledge in this area, the aim of this project is to establish a nation-wide network of investigators with expertise in pediatric lymphomas and AIDS and thus provide a mechanism for conduct of studies of the therapy and biology of these disorders. Cases of pediatric AIDS-associated lymphomas will be contributed to the network by the member institutions of the Pediatric Oncology Group (POG), by hemophilia treatment centers (HTCs) and AIDS Clinical Trials Units (ACTUs) located in POG centers, by selected institutions of the Children's Cancer Study Group (CCSG), by the TriServices (Army, Navy, Air Force) military pediatric HIV program, and by centers connected with cohorts of the Women Infant Transmission Study (WITS). By establishment of this network of federally-funded investigators, we expect to capture the majority of pediatrics AIDS-associated lymphomas occurring in the United States over the next three years. The objectives of our studies are to integrate Phase I-III therapeutic trials of anti-cancer and anti-retroviral treatments with correlative molecular biologic and virologic studies of the human immunodeficiency virus (HID), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and other herpes viruses. Our methodologic approach to the Phase II-III clinical trials will mirror the current front-line POG NHL protocols for newly-diagnosed non-HIV-infected non-Hodgkin's lymphoma patients, i.e., a control group for outcome analyses, while new agents and biologics will be tested in Phase I trials. Our hypothesis is that the host viral burden of HIV, EBV, HHV6 and CMV, assessed by quantitative culture of infectious virus and by quantitative polymerase chain reaction (PCR), will be directly related to toxicity of treatment with resultant reduction in dose intensity and increased likelihood of adverse outcome, either from disease progression or treatment-related death. We expect the resultant information to be important in future design of improved therapies which will minimize proliferation and viral-related toxicities. Complementing these clinical trials, we will establish centralized cell, sera, and tissue repositories and characterize and classify tumor tissues for origin, oncogene (c-myc) rearrangements, and viral-relatedness by PCR and in situ hybridization for viral genomes. All clinical and biologic data and analyses will be managed by a central statistical center, co-resident with the POG Statistical Office. By these coordinated efforts, we expect to foster effective treatments for pediatric AIDS-related lymphomas and facilitate collaborative interactions between laboratory scientists and clinicians.
