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Minimal Residual Disease Values Discriminate Between Low and High Relapse Risk in Children With B-Cell Precursor Acute Lymphoblastic Leukemia and an Intrachromosomal Amplification of Chromosome 21: The Austrian and German Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster (ALL-BFM) Trials

Andishe Attarbaschi, Georg Mann, Renate Panzer-Grümayer, Silja Röttgers, Manuel Steiner, Margit König, Eva Csinady, Michael N. Dworzak, Markus Seidel, Dasa Janousek, Anja Möricke, Carsten Reichelt, Jochen Harbott, Martin Schrappe, Helmut Gadner, Oskar A. Haas

From the Department of Pediatric Hematology and Oncology, St Anna Children's Hospital; the Children's Cancer Research Institute, Vienna, Austria; the Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen; and the Department of Pediatric Hematology and Oncology, Children's University Hospital, University Hospital Schleswig-Holstein, Campus Kiel, Germany

Corresponding author: Oskar A. Haas, MD, St Anna Children's Hospital, Kinderpitalgasse 6,Vienna, Austria, 1090; e-mail: oskar.haas{at}stanna.at

Purpose We aimed to identify relapse predictors in children with a B-cell precursor acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21), a novel genetic entity associated with poor outcome.

Patients and Methods We screened 1,625 patients who were enrolled onto the Austrian and German ALL–Berlin-Frankfurt-Münster (ALL-BFM) trials 86, 90, 95, and 2000 with ETV6/RUNX1-specific fluorescent in situ hybridization probes, and we identified 29 patient cases (2%) who had an iAMP21. Minimal residual disease (MRD) was quantified with clone-specific immunoglobulin and T-cell receptor gene rearrangements.

Results Twenty-five patients were good responders to prednisone, and all achieved remission after induction therapy. Eleven patients experienced relapse, which included eight who experienced relapse after cessation of front-line therapy. Six-year event-free and overall survival rates were 37% ± 14% and 66% ± 11%, respectively. Results of MRD analysis were available in 24 (83%) of 29 patients: nine (37.5%) belonged to the low-risk, 14 (58.5%) to the intermediate-risk, and one (4%) to the high-risk group. MRD results were available in 8 of 11 patients who experienced a relapse. Seven occurred among the 14 intermediate-risk patients, and one occurred in the high-risk patient.

Conclusion The overall and early relapse rates in the BFM study were lower than that in a previous United Kingdom Medical Research Council/Childhood Leukemia Working Party study (38% v 61% and 27% v 47%, respectively), which might result from more intensive induction and early reintensification therapy in the ALL-BFM protocols. MRD values were the only reliable parameter to discriminate between a low and high risk of relapse (P = .02).

Supported by the Deutsche Krebshilfe; the Österreichische Kinderkrebshilfe; the Research Program, "Genome Research for Health" of the Austrian Ministry of Education, Science, and Culture (Grants No. GZ 200.071/3-VI/2a/2002, and GZ 200.136/1-VI/1/2005); and the Fonds zur Förderung der wissenschaftlichen Forschung (FWF Grants No. P15150 and P17551B14).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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