The prognosis for Burkitt leukemia has improved steadily over the past thirty years with short intensive therapy utilizing high dose methotrexate and fractionated cyclophosphamide (Cairo et al Br J Haem, 2003, Patte et al Blood, 2001, Reiter et al Blood, 2005). The presence of CNS involvement at diagnosis with B-ALL is, however, associated with a poorer survival (3yr EFS 60%) as demonstrated previously in 235 children and adolescents with B-ALL (≥25% L3 cells) with or without CNS involvement randomized to standard intensity FAB/LMB therapy vs adjusted (decreased) intensity and maintenance therapy demonstrating an advantage to standard intensity therapy (Cairo et al ASH, 2004). We now analyze the results in 110 children and adolescents with B-ALL and no evidence of CNS involvement at diagnosis treated on FAB/LMB96 (4–6 mo TX). 110 patients, 18% 0–4, 47% 5–9, 29% 10–14 and 6% 15–20yrs of age, 77% male; 109/110 Burkitt histology (one Burkitt-like); 89% ≥2 LDH upper limits, 90% ≥ 70% L3 BM involvement. 44% were treated in COG, 38% SFOP and 18% in UKCCSG. The 4yr EFS and OS was 88±3.1% and 89±3.0%, respectively. Patients randomized to standard vs adjusted (decreased) intensity had a 4 yr EFS of 94±3.8% vs 88±4.8%, respectively (p=0.26). Overall, readjusted for randomized intensity of therapy, the 4 yr EFS was 91±3.1%. Response to reduction therapy with COP (cyclophosphamide, vincristine, prednisone) was assessed at day 7. Patients with a complete response (M1) vs incomplete response (20–99% reduction of BM L3 cells) had a similar outcome; (4yr EFS) CR vs IR (93±5 vs 88±2.9%) (p=0.51). Patients with a higher percentage of L3 blasts, (≥70% vs 25–69% bone marrow involvement), had an improved 4 yr EFS. 4 yr EFS was 90±3.0 vs 70±15% (p<0.06) and 4 yr OS 91±3.0 vs 70±15% (p<0.03). Elevated LDH ≥ 2NL at diagnosis had no impact on prognosis. Furthermore, there was a dismal outcome for patients who relapsed (10% 2 yr PFS). In summary, children and adolescents with isolated B-ALL have an excellent (>90% 4 yr EFS) prognosis with 6 months of standard intensity FAB/LMB therapy. Mature B-acute lymphoblastic leukemia (Burkitt) (B-ALL) should now be considered one of the most curable forms of childhood ALL. Furthermore, as therapy reduction has been unsuccessful in this patient group with B-ALL, future strategies should consider whether substitution of targeted immunotherapy might allow for chemotherapy intensity reduction (with reduced morbidity) in this population. The outcome is poor for the few patients who relapse and new therapeutic strategies are required for this small subgroup.