1. ¹Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
2. ²Institute of Human Genetics, Ruprecht-Karls University, Heidelberg, Germany
3. ³Pediatric Clinic, University of Milano-Bicocca, Ospedale Nuovo San Gerardo, and Childhood Leukemia Research Center M. Tettamanti, Monza, Italy
4. ⁴Children's Cancer Research Institute, Vienna, Austria
5. ⁵St Anna Children's Hospital, Vienna, Austria
6. ⁶Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
7. ⁷Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany
8. ⁸Department of Pediatrics, University of Padova, Padova, Italy
9. ⁹Department of Pediatric Hematology/Oncology and Oncology Laboratories, University Children's Hospital, Zurich, Switzerland
10. ¹⁰Children's Cancer Institute Australia for Medical Research, University of New South Wales, Randwick, New South Wales, Australia

Correspondence: Dr M Schrappe, Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Schwanenweg 20, Kiel 24105, Germany. E-mail: m.schrappe@pediatrics.uni-kiel.de

¹¹These authors contributed equally to this work.

Received 3 August 2007; Revised 20 December 2007; Accepted 3 January 2008; Published online 31 January 2008.

Abstract

Detection of minimal residual disease (MRD) is the most sensitive method to evaluate treatment response and one of the strongest predictors of outcome in childhood acute lymphoblastic leukemia (ALL). The 10-year update on the I-BFM-SG MRD study 91 demonstrates stable results (event-free survival), that is, standard risk group (MRD-SR) 93%, intermediate risk group (MRD-IR) 74%, and high risk group (MRD-HR) 16%. In multicenter trial AIEOP-BFM ALL 2000, patients were stratified by MRD detection using quantitative PCR after induction (TP1) and consolidation treatment (TP2). From 1 July 2000 to 31 October 2004, PCR target identification was performed in 3341 patients: 2365 (71%) patients had two or more sensitive targets (10^-4), 671 (20%) patients revealed only one sensitive target, 217 (6%) patients had targets with lower sensitivity, and 88 (3%) patients had no targets. MRD-based risk group assignment was feasible in 2594 (78%) patients: 40% were classified as MRD-SR (two sensitive targets, MRD negativity at both time points), 8% as MRD-HR (MRD 10^-3 at TP2), and 52% as MRD-IR. The remaining 823 patients were stratified according to clinical risk features: HR (n=108) and IR (n=715). In conclusion, MRD-PCR-based stratification using stringent criteria is feasible in almost 80% of patients in an international multicenter trial.