Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follow-up data. The analysis included data on 351 patients treated by standard chemotherapy according to 11 different successive and/or concomitant regimens. Complete remission (CR) was achieved in 299 patients (79%). Initial performance status, LDH level, immunophenotype, age, and risk group (defined according to Hoelzer's criteria) at diagnosis were of significant prognostic value for CR achievement. Median leukemia-free survival (LFS) was 14 months with a 3-year, a 5-year, and an 8-year LFS at 30%, 26%, and 24%, respectively. LFS was better in T cell lineage ALL than in B cell lineage ALL (P = 0.05). Younger age was also a favorable prognostic factor for LFS (P = 0.001). Philadelphia-positive (Ph+) ALL displayed a poor outcome since median LFS was 7 months with only 13% of survival at 3 years. Median overall survival (OS) of the entire cohort was 18 months with a 3-year, a 5-year, and an 8-year OS at 32%, 24%, and 22% respectively. Favorable prognostic factors for OS were younger age (P < 0.0001), and T cell lineage ALL (P = 0.001). Among non-T cell lineage ALL, standard-risk ALL confirmed a significant better outcome than high-risk ALL (P = 0.0003). It was apparent from this analysis that hazard rates for death and relapse were greatest in the first year, decreased substantially between years 1 and 2, then decrease further between years 2 and 3. Rates of death and relapse were quite low after 3-4 years. All patients relapsing after 3 years of CR were B or non-B non-T cell lineage ALL. Long-term survivors (LTS), defined as survival in CR > or =3 years, represented 23% of evaluable patients. Eighty-three patients remain alive in initial CR at >3 years, while only three were LTS after a second CR. Overall, no significant improvement was shown in terms of CR achievement and survival duration over the years. However, regarding survival, a significant improvement was demonstrated in T cell lineage ALL (P = 0.03). Furthermore, patients (aged less than 50 years) transplanted while in first CR did significantly better than those receiving only chemotherapy as post-remission therapy (P < 0.0001). The 3-year OS, after allogeneic transplantation in first CR, was 74% in T cell lineage ALL, while it was less than 50% in B cell lineage ALL. This single center study on a large cohort of ALL patients reflects the degree to which ALL treatment remains unsuccessful in adults. Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR.