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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

A Correction to this article was published on 08 April 2020

This article has been updated

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.

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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.

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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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