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  • Title: 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-Munster (ALL-BFM) trials.
    Author: Attarbaschi A, Mann G, Panzer-Grümayer R, Röttgers S, Steiner M, König M, Csinady E, Dworzak MN, Seidel M, Janousek D, Möricke A, Reichelt C, Harbott J, Schrappe M, Gadner H, Haas OA.
    Journal: J Clin Oncol; 2008 Jun 20; 26(18):3046-50. PubMed ID: 18565891.
    Abstract:
    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).
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