1. ¹Department of Hematology and Oncology, Robert-Roessle-Clinic at HELIOS Klinikum Berlin, Charité-Campus Buch, Germany
2. ²Laboratory of Pediatric Onco-Hematology, Department of Pediatrics, University Hospital of Padova, Padova, Italy
3. ³Department of Pediatric Hematology and Oncology, Children's Cancer Research Institute and St Anna Children's Hospital Vienna, Vienna, Austria
4. ⁴Department of Pediatrics, Tettamanti Research Center, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
5. ⁵Department of Pediatrics, University of Florence, Florence, Italy
6. ⁶Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany

Correspondence: Dr R Ratei, Department of Hematology, Oncology and Tumor Immunology, University Medical School Berlin, Charité, Campus-Buch, HELIOS Klinikum Berlin, Robert-Roessle-Clinic, Schwanebecker Chaussee 50, Berlin 13125, Germany. E-mail: richard.ratei@helios-kliniken.de

⁷These authors contributed equally this work.

Received 5 June 2008; Revised 1 October 2008; Accepted 14 October 2008; Published online 20 November 2008.

Abstract

Treatment response is a strong outcome predictor for childhood acute lymphoblastic leukemia (ALL). Here, we evaluated the predictive impact of flow cytometric blast quantification assays (absolute blast count, BC, and blast reduction rate, BRR) in peripheral blood (pB) and/or bone marrow (BM) at early time points of induction therapy (days 0, 8 and 15) on the remission status in the AIEOP-BFM-ALL 2000 protocol. At the single parameter level (905 patients), the strongest predictive parameter for the remission status as a dichotomous minimal residual disease (MRD) parameter (positive/negative) has been provided by the BC at day 15 in BM (cutoff: 17 blasts/l; 50 vs 15%; odds ratio: 5.6; 95% confidence interval: 4.1–7.6, P<0.001), followed by the BRR at day 15 in BM and by the BC at day 8 in pB (odds ratios: 3.8 and 2.6, respectively). In the multiple regression analysis (440 patients), BC in pB (d0 and d8) and in BM (d15) as well as BRR at day 8 in pB provided significantly contributing variables with an overall correct prediction rate of 74.8%. These data show that the quantitative assessment of early response parameters, especially absolute BCs at day 15 in BM, has a predictive impact on the remission status after induction therapy.