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Acute lymphoblastic leukemia

Flow cytometric detection of leukemic blasts in cerebrospinal fluid predicts risk of relapse in childhood acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology study

Leukemia volume 34, pages 336–346 (2020)Cite this article

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A Correction to this article was published on 08 April 2020

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Abstract

Central nervous system (CNS) involvement by cytospin is associated with increased risk of relapse in childhood acute lymphoblastic leukemia. We investigated if flow cytometric analysis of cerebrospinal fluid (CSF) at diagnosis improves the prediction of relapse. This prospective cohort study included patients (1.0–17.9 years) treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. CSF flow cytometry samples were obtained at 17 centers, preserved with Transfix®, and analyzed at a central laboratory. One-hundred and seventy-one (25.4%) of 673 patients were positive by flow cytometry (CNSflow+). The 4-year cumulative incidence of relapse was higher for patients with cytospin positivity (CNScyto+) (17.1% vs. 7.5%), CNSflow+ (16.5% vs. 5.6%), and cytospin and/or flow positivity (CNScomb+) (16.7% vs. 5.1%). In Cox regression analysis stratified by immunophenotype and minimal residual disease day 29 and adjusted by sex, predictors of relapse were age (hazard ratio [HR] 1.1, 95% CI 1.1–1.2, P < 0.001), white blood cell count at diagnosis (HR 1.4, 95% CI 1.1–1.6, P < 0.001), and CNScomb+ (HR 2.2, 95% CI 1.0–4.7, P = 0.042). Flow cytometric analysis of CSF improves detection of CNS leukemia, distinguishes patients with high and low risk of relapse, and may improve future risk stratification and CNS-directed therapy.

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Acknowledgements

We thank all Nordic and Baltic pediatric oncology centers for providing clinical data and CSF samples for flow cytometric analysis. We are grateful to the staff at the Laboratory of Pediatric Oncology and the Department of Immunology, Rigshospitalet, for their help with sample analysis and data registration. The study was funded by the Danish Childhood Cancer Foundation, Nordic Cancer Union, Rigshospitalet, Swedish Childhood Cancer Foundation, Danish Cancer Research Foundation, Cancer Research Foundation of Elna and Jørgen Fagerholt Pedersen, Axel Muusfeldt’s Foundation, Anders Hasselbalch’s Fight Leukemia Foundation, Otto Christensen’s Foundation, Memorial Foundation of Merchant M. Brogaard and Wife, Research Foundation of Hasselbalch and Lykkegaard Andersen, Memorial Foundation of Eva and Henry Frænkel, Dagmar Marshall’s Foundation, King Christian the Tenth Foundation, Memorial Trust Foundation of Thora and Viggo Grove.

Author information

Author notes

  1. These authors contributed equally: Maria Thastrup, Hanne Vibeke Marquart

Authors and Affiliations

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

    Maria Thastrup, Mette Levinsen, Kathrine Grell, Thomas Leth Frandsen & Kjeld Schmiegelow

  2. Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Hanne Vibeke Marquart

  3. Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    Kathrine Grell

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

    Jonas Abrahamsson

  5. Children and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark

    Birgitte Klug Albertsen

  6. Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

    Arja Harila-Saari

  7. Department of Pediatric and Adolescent Medicine, Turku University Hospital and Turku University, Turku, Finland

    Päivi Maria Lähteenmäki

  8. Department of Pediatrics, Oulu University Hospital and PEDEGO Research Unit, University of Oulu, Oulu, Finland

    Riitta Niinimäki

  9. Department of Pediatrics, Skåne University Hospital, Lund, Sweden

    Cornelis Jan Pronk

  10. Department of Pediatrics, Oslo University Hospital, Oslo, Norway

    Aina Ulvmoen

  11. Center for Pediatric Oncology and Hematology, Children’s hospital, Affiliate of Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, Lithuania

    Goda Vaitkevičienė

  12. Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki University Hospital, Helsinki, Finland

    Mervi Taskinen

  13. Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Kjeld Schmiegelow

  14. Department of Pediatric Hematology and Oncology, H.C. Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark

    Peder Wehner

  15. Department of Women’s and Children’s Health, Pediatrics, University of Uppsala, Uppsala, Sweden

    Britt-Marie Frost

  16. Department of Medical Biosciences, Genetics, Umeå University Hospital, Umeå, Sweden

    Ulrika Norén-Nyström

  17. Department of Pediatrics, Linköping University Hospital, Linköping, Sweden

    Mikael Behrendtz

  18. Department of Paediatrics, St. Olavs University Hospital Trondheim, Trondheim, Norway

    Bendik Lund

  19. Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland

    Jouni Pesola

  20. Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland

    Jouni Pesola

  21. Department of Pediatrics, Bergen Hospital, Bergen, Norway

    Dorota Malgorzata Wojcik

Authors
  1. Maria Thastrup
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Consortia

on behalf of the Nordic Society of Pediatric Hematology and Oncology (NOPHO)

  • Peder Wehner
  • , Britt-Marie Frost
  • , Ulrika Norén-Nyström
  • , Mikael Behrendtz
  • , Bendik Lund
  • , Jouni Pesola
  •  & Dorota Malgorzata Wojcik

Contributions

KS, HVM and ML designed the study. All authors contributed to sample collection. MThastrup and ML coordinated the study. MThastrup, HVM, and KG analyzed the data. MThastrup, HVM, KG and KS interpreted the data and wrote the first draft of the manuscript. All authors critically reviewed the manuscript and approved the final draft for submission.

Corresponding author

Correspondence to Kjeld Schmiegelow.

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Thastrup, M., Marquart, H.V., Levinsen, M. et al. Flow cytometric detection of leukemic blasts in cerebrospinal fluid predicts risk of relapse in childhood acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology study. Leukemia 34, 336–346 (2020). https://doi.org/10.1038/s41375-019-0570-1

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