BACKGROUND Adult B/L3-ALL is a rare disease subset characterized by an aggressive clinical course and a poor response to conventional adult ALL-type chemotherapy. Recent data from the GMALL Group showed that prognosis can be improved with an innovative treatment regimen. In the current retrospective survey we focus on therapeutic results obtained at our Institutions during a 15-year period with ALL-type regimens in 34 adults with either B/L3-ALL or advanced-stage Burkitt's lymphoma. METHODS Five successive ALL treatment programs were developed. They included a homogeneous induction phase with early intrathecal chemoprophylaxis, multidrug postremission consolidation followed by cranial irradiation (4 trials), high-dose chemotherapy plus autografting (2 trials), late consolidation (2 trials), and variable-length maintenance (4 trials). Early response and prolonged disease-free survival rates were analyzed according to selected clinical and therapeutic variables. RESULTS Overall, a complete remission was achieved in 62%, with a median duration of 1.6 years and a 10-year remission rate of 49%. A diagnosis of B/L3-ALL (p = 0.007), the use of idarubicin instead of adriamycin during induction (p = 0.018), a serum creatinine < 1.6 mg/dL, and an uninvolved central nervous system were associated with higher response rates. As regards long-term disease-free survival, results were significantly better in patients with < 1 x 10(9)/L L3/blast cells in the peripheral blood (p = 0.0029) and/or aged < 50 years (p = 0.04), and in those consolidated with the most recent rotational high-dose plus peripheral blood stem cell autotransplant regimen. CONCLUSIONS According to the results presented, ALL-like regimens may still represent a worthwhile therapeutic choice. The use of idarubicin during induction, the prognostic subclassification of patients, a careful control of dysmetabolic complications, the selection of the proper chemo-radioprevention for meningeal disease and perhaps the introduction of high-dose chemotherapy supported by autologous stem cell rescue appear to be the mainstay of further improvements.