Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The <scp>NOPHO ALL</scp>2008 experience

Abstract

Summary The population‐based Nordic/Baltic acute lymphoblastic leukaemia ( ALL ) Nordic Society for Paediatric Haematology and Oncology ( NOPHO ) ALL 2008 protocol combined minimal residual disease ( MRD )‐driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL . Patients with MRD ≥5% at end of induction or ≥10 −3 at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation ( HCT ) in first remission. After at least three high risk blocks a total of 71 children received HCT , of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre‐ HCT MRD results, 22 were MRD ‐positive, one with MRD ≥10 −3 . After a median follow‐up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [ CI ]: 10·5–47·7) for MRD ‐positive versus 5·1% (95% CI : 1·3–19·2), P = 0·02) for MRD ‐negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI : 1·6–51·0, P = 0·012). Non‐relapse mortality did not differ between the two groups, resulting in disease‐free survival of 85·6% (95% CI : 75·4–97·2) and 67·4% (95% CI : 50·2–90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre‐ HCT MRD ‐positive patients.