Recent approaches in acute lymphoblastic leukemia in adults.

In the last decades outcome of adult acute lymphoblastic leukemia (ALL) has improved considerably. In large multicenter studies remission rates range from 75% to 89%, and long-term leukemia-free survival (LFS) from 28% to 39%. Major progress has also been made regarding better characterization of subtypes of ALL. Complete diagnostic procedures are essential to identify these subtypes which have significant differences in clinical and laboratory features and prognosis. LFS of > 50% can be expected in favorable subtypes such as T-ALL or mature B-ALL, while LFS of < 20% is expected in Ph/BCR-ABL positive ALL. Prognostic factors can be used for risk stratification and selection of treatment strategies can be adapted to the subtype and relapse risk. This includes measurement of minimal residual disease (MRD) to evaluate individualized treatment strategies adapted to the molecular response. Several new approaches for improvement in chemotherapy and stem cell transplantation (SCT) are under investigation. They include the use of intensified anthracyclines, asparaginase, cyclophosphamide or high-dose cytarabine during induction and intensive rotational chemotherapy during consolidation. Also SCT - mainly from sibling donors - is now part of standard treatment of de novo ALL, although it remains open whether indications should be based on prognostic factors or whether SCT should be offered to all patients with sibling donor. However, substantial progress can only be achieved by new, experimental strategies. These include new approaches for SCT, such as nonmyeloablative SCT, measurement of MRD, causal treatment with molecular targeting, e.g. with kinase inhibitors, and antibody therapy.