Improved Outcome for ALL by Prolonging Therapy for Deletion and Decreasing Therapy for Other Risk Groups.

Purpose: The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three minimal residual disease-defined risk groups: standard risk, medium risk (MR), and high risk. -deleted (del) ALL in the largest MR group still showed poor outcome, in line with protocols worldwide, accounting for a high number of overall relapses. ALL10 showed high toxicity in Down syndrome (DS) and excellent outcome in ALL. Poor prednisone responders (PPRs) were treated as high risk in ALL10. In ALL11, we prolonged therapy for del from 2 to 3 years. We reduced therapy for DS by omitting anthracyclines completely, for in intensification, and for PPR by treatment as MR.

Methods: Eight hundred nineteen patients with ALL (age, 1-18 years) were enrolled on ALL11 and stratified as in ALL10. Results were compared with those in ALL10.

Results: The five-year overall survival (OS), event-free survival (EFS), cumulative risk of relapse (CIR), and death in complete remission on ALL11 were 94.2% (SE, 0.9%), 89.0% (1.2), 8.2% (1.1), and 2.3% (0.6), respectively. Prolonged maintenance for del MR improved 5-year CIR by 2.2-fold (10.8% 23.4%; = .035) and EFS (87.1% 72.3%; = .019). Landmark analysis at 2 years from diagnosis showed a 2.9-fold reduction of CIR (25.6%-8.8%; = .008) and EFS improvement (74.4%-91.2%; = .007). Reduced therapy did not abrogate 5-year outcome for (EFS, 98.3%; OS, 99.4%), DS (EFS, 87.0%; OS, 87.0%), and PPR (EFS, 81.1%; OS, 94.9%).

Conclusion: Children with del ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with , DS, and PPR ALL. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.