The non-Hodgkin lymphomas are a heterogeneous group of malignancies frequently affecting the lymphoid system. This group of diseases is increasing rapidly in incidence, especially among older individuals. The diseases are generally treatable, but less than 30 percent of patients are permanently cured. The focus of my research has been directed at two general aspects of lymphoma.
Improving Treatment for Lymphoma
The Univeresity of Arizona Cancer Center has a long history of developing new therapy for patients with non-Hodgkin lymphoma. Studies began in the 1970s have only recently matured and have defined a new benchmark for treating patients with clinically localized forms of aggressive histologies of non-Hodgkin's lymphomas. The pilot work done at the Cancer Center demonstrated that initial chemotherapy was effective in eliminating micro-metastatic disease in patients who had apparent localized disease.
Subsequent randomized trials coordinated at the Cancer Center and conducted by the Southwest Oncology Group confirmed that initial combination chemotherapy, followed by radiotherapy, is the best available standard therapy in terms of efficacy and toxicity. Most patients with non-Hodgkin lymphomas, however, present with very advanced disease. Most of these patients eventually recur following initial treatment, and at the time of recurrence, have resistance to multiple chemotherapy agents. Work continues at the UA Cancer Center to reverse acquired drug resistance by the use of chemosensitizers. New studies are activated as new agents are developed to reverse acquired drug resistance in patients with recurrent lymphoma.
Lymphoma Cell Surface Chemistry and Prognosis
A series of studies has been conducted at the UA Cancer Center in collaboration with Dr. Thomas M. Grogan in the Department of Pathology to determine the clinical relevance of several cell surface proteins. These studies have correlated proteins that are partly responsible for the host response, proteins associated with cell proliferation, proteins associated with specific sites of disease involvement, and proteins associated with clinical drug resistance with prognosis. In two cases, this information has led to specific changes in treatment designed to intervene with the abnormal protein chemistry. The first example is a protein detected by a monoclonal antibody called Ki-67, which when overexpressed, resulted in a very poor prognosis. A clinical trial is now under way to treat such patients with initial high-dose chemotherapy and stem cell rescue. A second example is the discovery that loss of certain histocompatibility antigens resulted in a corresponding decrease in tumor-infiltrating lymphocytes. A study was completed using gene therapy to try to restore the immune response by transfecting the B7 gene.