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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

Thastrup, Maria ; Marquart, Hanne Vibeke ; Levinsen, Mette ; Grell, Kathrine ; Abrahamsson, Jonas ; Albertsen, Birgitte Klug ; Frandsen, Thomas Leth ; Harila-Saari, Arja ; Lähteenmäki, Päivi Maria and Niinimäki, Riitta , et al. (2019) In Leukemia
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... (More)

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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@article{47eb7937-73de-404c-99d0-728846048e45,
  abstract     = {<p>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 (CNS<sub>flow+</sub>). The 4-year cumulative incidence of relapse was higher for patients with cytospin positivity (CNS<sub>cyto+</sub>) (17.1% vs. 7.5%), CNS<sub>flow+</sub> (16.5% vs. 5.6%), and cytospin and/or flow positivity (CNS<sub>comb+</sub>) (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 &lt; 0.001), white blood cell count at diagnosis (HR 1.4, 95% CI 1.1–1.6, P &lt; 0.001), and CNS<sub>comb+</sub> (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.</p>},
  author       = {Thastrup, Maria and Marquart, Hanne Vibeke and Levinsen, Mette and Grell, Kathrine and Abrahamsson, Jonas and Albertsen, Birgitte Klug and Frandsen, Thomas Leth and Harila-Saari, Arja and Lähteenmäki, Päivi Maria and Niinimäki, Riitta and Pronk, Cornelis Jan and Ulvmoen, Aina and Vaitkevičienė, Goda and Taskinen, Mervi and Schmiegelow, Kjeld and Wehner, Peder and Frost, Britt Marie and Norén-Nyström, Ulrika and Behrendtz, Mikael and Lund, Bendik and Pesola, Jouni and Wojcik, Dorota Malgorzata},
  issn         = {0887-6924},
  language     = {eng},
  month        = {09},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {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},
  url          = {http://dx.doi.org/10.1038/s41375-019-0570-1},
  doi          = {10.1038/s41375-019-0570-1},
  year         = {2019},
}