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Acute lymphoblastic leukemia

Flowcytometric evaluation of cerebrospinal fluid in childhood ALL identifies CNS involvement better then conventional cytomorphology

Leukemia volume 35, pages 1773–1776 (2021)Cite this article

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Due to improved therapy, childhood Acute Lymphoblastic Leukemia (ALL) nowadays has a good prognosis with long-term event-free survival and overall survival rates over 80% and 90%, respectively [1,2,3]. Nevertheless, about 15% of patients will eventually relapse with central nervous system (CNS) involvement in ~25–30% [1, 4], despite prophylactic treatment of the CNS [5, 6]. The presence of low numbers of leukemic blasts in the CSF without elevated cell counts (so called CNS2) may be a significant risk factor for CNS relapse [7, 8].

Since CNS involvement at diagnosis leads to extra intrathecal medication during induction treatment, appropriate and reliable detection of the presence of ALL cells in CSF is a prerequisite.

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Fig. 1: Relapse-free survival for ALL patients according to CNS status.

References

  1. Pieters R, de Groot-Kruseman H, Van der Velden V, Fiocco M, van den Berg H, de Bont E, et al. Successful therapy reduction and intensification for childhood acute lymphoblastic leukemia based on minimal residual disease monitoring: study ALL10 From the Dutch Childhood Oncology Group. J Clin Oncol. 2016;34:2591–601.

    Article  Google Scholar 

  2. Vrooman LM, Stevenson KE, Supko JG, O’Brien J, Dahlberg SE, Asselin BL, et al. Postinduction dexamethasone and individualized dosing of Escherichia coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study-Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol. 2013;31:1202–10.

    Article  CAS  Google Scholar 

  3. Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014;32:174–84.

    Article  CAS  Google Scholar 

  4. van der Velden VH, de Launaij D, de Vries JF, de Haas V, Sonneveld E, Voerman JS, et al. New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia. Br J Haematol. 2016;172:769–81.

    Article  Google Scholar 

  5. Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med. 2009;360:2730–41.

    Article  CAS  Google Scholar 

  6. Veerman AJ, Kamps WA, van den Berg H, van den Berg E, Bokkerink JP, Bruin MC, et al. Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004). Lancet Oncol. 2009;10:957–66.

    Article  CAS  Google Scholar 

  7. Dutch Childhood Oncology Group, te Loo DM, Kamps WA, van der Does-van den Berg A, van Wering ER, de Graaf SS. Prognostic significance of blasts in the cerebrospinal fluid without pleiocytosis or a traumatic lumbar puncture in children with acute lymphoblastic leukemia: experience of the Dutch Childhood Oncology Group. J Clin Oncol. 2006;24:2332–6.

    Article  Google Scholar 

  8. Burger B, Zimmermann M, Mann G, Kuhl J, Loning L, Riehm H, et al. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol. 2003;21:184–8.

    Article  Google Scholar 

  9. Quijano S, Lopez A, Manuel Sancho J, Panizo C, Deben G, Castilla C, et al. Identification of leptomeningeal disease in aggressive B-cell non-Hodgkin’s lymphoma: improved sensitivity of flow cytometry. J Clin Oncol. 2009;27:1462–9.

    Article  CAS  Google Scholar 

  10. Thastrup M, Marquart HV, Levinsen M, Grell K, Abrahamsson J, Albertsen BK, 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. 2020;34:336–46.

    Article  CAS  Google Scholar 

  11. van Dongen JJ, Lhermitte L, Bottcher S, Almeida J, van der Velden VH, Flores-Montero J, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012;26:1908–75.

    Article  Google Scholar 

  12. Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood. 2017;129:347–57.

    Article  CAS  Google Scholar 

  13. Vora A, Andreano A, Pui CH, Hunger SP, Schrappe M, Moericke A, et al. Influence of cranial radiotherapy on outcome in children with acute lymphoblastic leukemia treated with contemporary therapy. J Clin Oncol. 2016;34:919–26.

    Article  CAS  Google Scholar 

  14. Kamps WA, Bokkerink JP, Hahlen K, Hermans J, Riehm H, Gadner H, et al. Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988-1991). Blood. 1999;94:1226–36.

    CAS  PubMed  Google Scholar 

  15. Kamps WA, Bokkerink JP, Hakvoort-Cammel FG, Veerman AJ, Weening RS, van Wering ER, et al. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996). Leukemia. 2002;16:1099–111.

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to Dr. Elisabeth van Wering for useful discussions in the starting phase of this project. We thank the technicians of the DCOG, pediatric oncology laboratory (Erasmus MC), and Laboratory Medical Immunology (Erasmus MC) for their support.

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Authors and Affiliations

  1. Dutch Childhood Oncology Group, Utrecht, The Netherlands

    Valérie de Haas, Rob Pieters, Alita J. van der Sluijs-Gelling, Hester A. de Groot-Kruseman & Edwin Sonneveld

  2. Prinses Máxima Centrum, Utrecht, The Netherlands

    Valérie de Haas, Rob Pieters, C. Michel Zwaan, Hester A. de Groot-Kruseman & Edwin Sonneveld

  3. Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    C. Michel Zwaan & Rolinda L. Stigter

  4. Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Vincent H. J. van der Velden

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  1. Valérie de Haas
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Contributions

AJS-G and RLS performed experiments; HAG-K, ES, and VH performed analyses; VH, RP, CMZ. and VHJV designed research and wrote the paper, with help from the other authors; and all authors have seen and reviewed the paper and approved the final version.

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Correspondence to Valérie de Haas.

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de Haas, V., Pieters, R., van der Sluijs-Gelling, A.J. et al. Flowcytometric evaluation of cerebrospinal fluid in childhood ALL identifies CNS involvement better then conventional cytomorphology. Leukemia 35, 1773–1776 (2021). https://doi.org/10.1038/s41375-020-01029-9

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