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Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse

Abstract

Using flow cytometric techniques capable of detecting 0.01% leukemic cells, we prospectively studied minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) after first relapse. At the end of remission reinduction, 41 patients had a bone marrow sample adequate for MRD studies; 35 of these were in morphologic remission. Of the 35 patients, 19 (54%) had MRD 0.01%, a finding that was associated with subsequent leukemia relapse. The 2-year cumulative incidence of second leukemia relapse was 70.2±12.3% for the 19 MRD-positive patients and 27.9±12.4% for the 16 MRD-negative patients (P=0.008). Among patients with a first relapse off therapy, 2-year second relapse rates were 49.1±17.8% in the 12 MRD-positive and 0% in the 11 MRD-negative patients (P=0.014); among those who received only chemotherapy after first relapse, the 2-year second relapse rates were 81.5±14.4% (n=12) and 25.0±13.1% (n=13), respectively (P=0.004). Time of first relapse and MRD were the only two significant predictors of outcome in a multivariate analysis. We conclude that MRD assays should be used to guide the selection of postremission therapy in patients with ALL in first relapse.

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Acknowledgements

We thank Peixin Liu and Mo Mehrpooya for technical assistance and Yinmei Zhou for assistance with the statistical analysis. This work was supported by Grants CA60419 and CA21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities (ALSAC). C-H Pui is supported by the American Cancer Society FM Kirby Clinical Research Professorship.

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Coustan-Smith, E., Gajjar, A., Hijiya, N. et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse. Leukemia 18, 499–504 (2004). https://doi.org/10.1038/sj.leu.2403283

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