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Minimal Residual Disease

The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia

Leukemia volume 20, pages 1783–1789 (2006)Cite this article

Abstract

We assessed by multiparametric flow cytometry the levels of minimal residual disease (MRD) in 100 adult patients with acute myelogenous leukemia (AML) achieving complete remission after intensive chemotherapy. The aim of the study was to determine the optimal threshold, in terms of residual leukemic cells, and the time point of choice, that is, post-induction (post-Ind) or post-consolidation (post-Cons), able to better predict outcome. By applying the maximally selected log-rank statistics, the threshold discriminating MRD− from MRD+ cases was set at 3.5 × 10−4 residual leukemic cells, a level that allowed the identification of distinct subgroups of patients, both at post-Ind and post-Cons time points. Post-Cons MRD− patients had a superior outcome in terms of relapse rate, overall survival (OS) and relapse-free survival (RFS) (P<0.001, for all comparisons), regardless of the MRD status after induction. In particular, patients entering MRD negativity only after consolidation showed the same outcome as those achieving early negativity after induction. Multivariate analysis, including karyotype, age, MDR1 phenotype, post-Ind and post-Cons MRD levels, indicated that the post-Cons MRD status independently affected relapse rate, OS and RFS (P<0.001, for all comparisons). In conclusion: (1) the threshold of 3.5 × 10−4 is valid in discriminating risk categories in adult AML and (2) post-Cons MRD assessment is critical to predict disease outcome.

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Acknowledgements

The study was supported in part by Ministero della Salute (Ricerca Finalizzata IRCCS and ‘Alleanza contro il Cancro’), Rome, Italy. We thank Antonella Zucchetto, Clinical and Experimental Hematology Research Unit, CRO Aviano for her support in statistical analyses.

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Authors and Affiliations

  1. Department of ‘Biopatologia e Diagnostica per Immagini’, Policlinico Tor Vergata and Ospedale S Eugenio, Rome, Italy

    F Buccisano, L Maurillo, G Del Poeta, M I Del Principe, M C Cox, P Panetta, M Irno Consalvo, C Mazzone, B Neri, L Ottaviani, D Fraboni, A Tamburini, F Lo-Coco, S Amadori & A Venditti

  2. Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, IRCCS., Aviano (PN), Italy

    V Gattei

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Correspondence to A Venditti.

Additional information

Presented in part at the 46th ASH meeting, 4–7 December 2004, San Diego, CA, USA.

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Buccisano, F., Maurillo, L., Gattei, V. et al. The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia. Leukemia 20, 1783–1789 (2006). https://doi.org/10.1038/sj.leu.2404313

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