We analyzed the long-term outcome of 1011 patients treated in five successive clinical trials (Total Therapy Studies 11, 12, 13A, 13B and 14) between 1984 and 1999. The event-free survival improved significantly (p=0.003) from the first two trials conducted in the 1980s to the three more recent trials conducted in the 1990s. Approximately 75% of patients treated in the 1980s and 80% in the 1990s were cured. Early intensive triple intrathecal therapy, together with more effective systemic therapy, including consolidation and reinduction treatment (Studies 13A and 13B) as well as dexamethasone (Study 13A), resulted in a very low rate of isolated central-nervous-system relapse rate (<2%), despite the reduced use of cranial irradiation. Factors consistently associated with treatment outcome were age, leukocyte count, immunophenotype, DNA index, and minimal residual disease level after remission induction treatment. Because of concerns about therapy-related secondary myeloid leukemia and brain tumors, in our current trials we reserve the use of etoposide for patients with refractory or relapsed leukemia undergoing hematopoietic stem cell transplantation, and cranial irradiation for those with CNS relapse. The next main challenge is to further increase cure rates while improving quality of life for all patients.

Background: Weak associations between total and LDL cholesterol and ischaemic stroke compared with coronary heart disease (CHD) are at odds with the similar effectiveness of statin drugs in preventing ischaemic stroke and CHD, suggesting that other lipid sub-fractions that are affected by statins might be better predictors of ischaemic stroke. Apolipoprotein B levels are reduced by statins and are a stronger predictor of CHD than total and LDL cholesterol in patients both on and off statins. However, there are very few published data on apolipoproteins and stroke risk and no studies in patients with previous transient ischaemic attack (TIA). Methods: We performed a prospective cohort study of the associations of baseline total cholesterol, LDL, HDL, apolipoproteins A1 and B (apo A1; apo B) and risk of ischaemic stroke in 261 patients with previous TIA. Cox proportional hazards models were used to determine crude and multivariate-adjusted hazard ratios (HR) above versus below median values at 10-years follow-up. Results: The apo B/apo A1 ratio was the strongest independent predictor of ischaemic stroke (HR = 2.94, 95% CI 1.43–5.88, p = 0.003) followed by apo B (HR = 2.26, 95% CI 1.16–4.38, p = 0.02). The associations between total cholesterol, LDL, HDL, LDL/HDL ratio and apo A1 and ischaemic stroke risk did not reach statistical significance. Conclusions: Apo B and the apo B/apo A1 ratio are predictive of ischaemic stroke in patients with previous TIA. Further studies are required to determine whether the prognostic value of apolipoprotein levels is maintained in patients on statins.