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Acute lymphoblastic leukemia

Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia

Leukemia volume 33, pages 1324–1336 (2019)Cite this article

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A Correction to this article was published on 10 December 2019

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Abstract

Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10−3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4–9.0, p = 0.008) for day 29 FCM-MRD ≥ 10−3 and 5.6 (95% CI 2.0–16, p = 0.001) for PCR-MRD ≥ 10−3 compared with MRD < 10−3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10−4–<10−3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10−4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10−4 had a cumulative incidence of relapse of 2.3% (95% CI 0–6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.

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  • 10 December 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

The authors would like to thank all NOPHO FCM-MRD and PCR-MRD laboratories in the Nordic and Baltic countries for their excellent and high-quality laboratory work and data analysis. Furthermore, the authors would like to thank all the clinicians in the Departments of Pediatric and Adult Hematology in the Nordic and Baltic countries for their thorough and dedicated care and treatment of the patients in the NOPHO ALL2008 protocol.

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Authors and Affiliations

  1. Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    S. Modvig, H. O. Madsen & H. V. Marquart

  2. Helsinki University Ctrl. Hospital, Helsinki, Finland

    S. M. Siitonen

  3. Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark

    S. Rosthøj

  4. Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, ON, Canada

    A. Tierens

  5. Department of Pathology, University Hospital of Oslo, Oslo, Norway

    A. Tierens

  6. Department of Clinical Chemistry and Laboratory Division, University of Turku and Turku University Hospital, Turku, Finland

    V. Juvonen

  7. Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway

    L.T.N. Osnes

  8. Department of Pathology, Laboratory of Molecular Pathology, Oslo University Hospital, Oslo, Norway

    H. Vålerhaugen

  9. Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden

    M. Hultdin

  10. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

    I. Thörn & M. Marincevic

  11. Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania

    R. Matuzeviciene

  12. Centre of Laboratory Medicine, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania

    R. Matuzeviciene

  13. Hematology, Oncology and Transfusion Medicine Centre, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania

    M. Stoskus

  14. Department of Clinical Chemistry, Sahlgrenska University Hospital, and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    L. Fogelstrand

  15. Department of Clinical Immunology, North Estonia Medical Centre, Tallinn, Estonia

    A. Lilleorg

  16. Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    N. Toft

  17. Childrenʼs Hospital, Landspitali University Hospital, Reykjavik, Iceland

    O. G. Jónsson

  18. Tallinn Childrenʼs Hospital, Tallinn, Estonia

    K. Pruunsild

  19. Childrenʼs Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania

    G. Vaitkeviciene

  20. Department of Pediatrics, Helsinki University Childrenʼs Hospital and University of Helsinki, Helsinki, Finland

    K. Vettenranta

  21. Department of Pediatrics, St. Olavs University Hospital and Department of Clinical and Molecular Medicine, NTNU, Trondheim, Norway

    B. Lund

  22. Institution of Clinical Sciences, Department of Pediatrics, Sahlgrenska University Hospital, Gothenburg, Sweden

    J. Abrahamsson

  23. Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    K. Schmiegelow

  24. The Institute of Clinical medicine, The Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark

    K. Schmiegelow

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  1. S. Modvig
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Correspondence to H. V. Marquart.

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Modvig, S., Madsen, H.O., Siitonen, S.M. et al. Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia. Leukemia 33, 1324–1336 (2019). https://doi.org/10.1038/s41375-018-0307-6

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