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Leukemia. 2019 Sep 18. doi: 10.1038/s41375-019-0570-1. [Epub ahead of print]

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.

Author information

1
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
2
Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
3
Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
4
Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden.
5
Children and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark.
6
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
7
Department of Pediatric and Adolescent Medicine, Turku University Hospital and Turku University, Turku, Finland.
8
Department of Pediatrics, Oulu University Hospital and PEDEGO Research Unit, University of Oulu, Oulu, Finland.
9
Department of Pediatrics, Skåne University Hospital, Lund, Sweden.
10
Department of Pediatrics, Oslo University Hospital, Oslo, Norway.
11
Center for Pediatric Oncology and Hematology, Children's hospital, Affiliate of Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, Lithuania.
12
Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki University Hospital, Helsinki, Finland.
13
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. kjeld.schmiegelow@regionh.dk.
14
Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. kjeld.schmiegelow@regionh.dk.

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.

PMID:
31534171
DOI:
10.1038/s41375-019-0570-1

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