HIV and Malignancies

Among the most devastating neurologic complication of HIV is primary CNS lymphoma (PCNSL), an AIDS-defining illness usually associated with short survival. Establishing the diagnosis of AIDS-related PCNSL can be difficult for a number of reasons, including the fact that results of neuro-imaging including MRI and PET as well as EBV evaluations are non-specific and established cerebrospinal fluid (CSF) tests lack specificity and sensitivity. Moreover, standard interventions for AIDS-related PCNSL have not been improved upon in decades. The goal of this proposal is to apply new technologies to the diagnosis and treatment of AIDS-related PCNSL and to build upon the progress made during the past seven months of support. We plan to validate candidate metabolic biomarkers of CNS lymphoma which we identified in our pilot metabolomic profiling study and to apply this information in the first metabolic imaging analysis of CNS lymphoma, in collaboration with Dr. John Kurhanewicz. We hypothesize that identification of metabolic biomarkers in CSF in HIV will advance diagnostic testing in the evaluation of HIV patients with focal brain lesions, not only via CSF-based tests but also facilitate technical advances in metabolic neuroimaging for improved, non-invasive diagnostic accuracy of CNS lymphoma. Finally, we have now demonstrated that antagonism of CXCR4 via AMD3100 significantly prolongs survival in a Burkitt's lymphoma model. We plan to extend these results via evaluations in intracranial xenografts derived from meningeal lymphomas from patients, and to optimize efficacy via modifications in dosing, administration and in combination with chemotherapy. These studies have the potential to lead to early phase trials in metabolic neuroimaging and intervention for AIDS-related CNS lymphoma developed through the AIDS Malignancy Consortium.