A multi-drug chemotherapy (APO) protocol incorporating doxorubicin was used to treat 12 patients (median age 19 years) with lymphoblastic lymphoma. The APO protocol consisted of intensive induction and consolidation phases, prophylactic CNS treatment, and 24 months of maintenance therapy. Eleven patients had an anterior mediastinal mass, while T cell markers were found on the lymphoma cells in eight of the nine cases tested. Two patients had initial CNS involvement, with one also having bone marrow replacement. Complete remission was obtained in all patients, with no deaths due to treatment toxicity. There have been four relapses, one in the patient with initial CNS and leukemic disease, two in abdominal sites, and in the mediastinum in one patient. With a median follow-up time of 30 months from diagnosis, 67% of patients remain alive in first remission. These results indicate that the APO protocol provides a highly effective approach to the management of this high grade lymphoma in adolescents and adults.