Risk/MRD adapted GMALL trials in adult ALL.

The German Multicenter Study Group for Adult ALL (GMALL) conducts since 1984 trials with risk adapted study design. The model of conventional prognostic factors comprises now WBC, age, immunophenotype, cytogenetics and molecular genetics. Risk stratification according to these factors allows a highly significant prediction of relapse risk in adult ALL. In the recent GMALL study minimal residual disease (MRD) was added to the risk model. Trials in childhood and adult ALL showed convincingly that MRD is a relevant and independent prognostic factor. It is of particular value in standard risk (SR) patients as defined by conventional factors. In the current GMALL study a risk stratification according to conventional factors is followed by a MRD based stratification in SR patients. Whereas high and very high risk patients receive a stem cell transplantation (SCT) in first CR after induction and first consolidation, SR patients receive cyclic consolidation therapy for one year with MRD monitoring. At the end of the first year a stratification according to course and level of MRD takes place. Treatment is stopped in patients with low risk whereas in high risk patients a SCT is planned. Patients who cannot be allocated to either group are treated as intermediate risk and receive one year of intensified maintenance therapy. Preliminary results show that MRD based risk stratification is feasible and that the treatment recommendations for MRD based risk groups are reasonable. In the future however an earlier identification of high risk patients (after 4 months) will be attempted.