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Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia

Leukemia volume 17, pages 138–148 (2003)Cite this article

Abstract

Using flow cytometry (FC) and live gate (LG) analysis we have followed levels of minimal residual disease (MRD) in the bone marrow (BM) of 70 consecutive patients with childhood acute lymphoblastic leukemia (59 B precursor ALL and 11 T-ALL) treated according to the Nordic (NOPHO-92) protocols. Thorough studies of B and T cell antigen expression patterns in normal BM performed during BIOMED 1 Concerted Action on MRD, made it possible to tailor individual protocols of marker combinations for follow-up in 97% of patients. In 12% of LG analyses, the numbers of cells exceeded 106 and in 82% exceeded 105, giving the sensitivity level of MRD detection 10−5 and 10−4, respectively. The median follow-up time was 53 months. Patients with MRD levels ≥0.01% at follow-up time-points during and after first induction, and at the end of treatment had significantly lower disease-free survival by comparison to patients with MRD values <0.01%. Seven of nine patient with recurrence in the BM showed under treatment persisting MRD levels ≥0.01% of BM cells. This was also observed in another two patients with infant leukemia who relapsed. In conclusion, the investigation of levels and the dynamics of MRD by sensitive and quantitative FC can provide a basis for further clinical studies for at least upgrading of therapy.

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Acknowledgements

This study was supported by grants from Swedish Cancer Society (Cancerfonden), Swedish Childhood Cancer Society (Barncancerfonden) and Stockholm County Council. The excellent technical assistance of Ms Inger Bodin, Yrsa Bringensparr, Marianne Lagnefelt, Britt Lundh, Shala Tarahumi, and Margareta Waern is gratefully acknowledged. We thank Mr Lewis Edgel for the help with editing the manuscript and the graphics. We thank Caltag Laboratories (San Francisco, CA, USA) and Dakopatts (Glostrup, Denmark) for kind donation of monoclonal antibodies for this study and Becton Dickinson (Stockholm, Sweden) for computer support.

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  1. Department of Pathology, Karolinska Hospital and Institutet, Stockholm, Sweden

    E Björklund, J Mazur & A Porwit-MacDonald

  2. Department of Epidemiology, National Research Institute of Mother and Child, Warsaw, Poland

    J Mazur

  3. Childhood Cancer Research Unit, Dept of Women and Child Health, Karolinska Hospital and Institutet, Stockholm, Sweden

    S Söderhäll

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Björklund, E., Mazur, J., Söderhäll, S. et al. Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia. Leukemia 17, 138–148 (2003). https://doi.org/10.1038/sj.leu.2402736

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