Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

Authors

  • Mette Levinsen MD,

    1. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Mervi Taskinen MD, PhD,

    1. Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland
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  • Jonas Abrahamsson MD, PhD,

    1. Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden
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  • Erik Forestier MD, PhD,

    1. Department of Medical Biosciences, Clinical Genetics, Umeå University, Umeå, Sweden
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  • Thomas L. Frandsen MD, PhD,

    1. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Arja Harila-Saari MD, PhD,

    1. Department of Pediatrics, University Hospital, Oulu, Finland
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  • Mats Heyman MD, PhD,

    1. Department of Pediatrics, Astrid Lindgrens Hospital, Stockholm, Sweden
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  • Olafur G. Jonsson MD,

    1. Department of Pediatrics, University Hospital, Reykjavík, Iceland
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  • Päivi M. Lähteenmäki MD, PhD,

    1. Department of Paediatrics, Turku University Hospital, Turku, Finland
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  • Birgitte Lausen MD, PhD,

    1. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Goda Vaitkevičienė MD, PhD,

    1. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark
    2. Center for Oncology and Hematology, Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania
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  • Ann Åsberg MD, PhD,

    1. Department of Pediatrics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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  • Kjeld Schmiegelow MD, PhD,

    Corresponding author
    1. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark
    2. The Institute of Clinical Medicine, The Faculty of Medicine, University of Copenhagen, Denmark
    • Correspondence to: Kjeld Schmiegelow, Department of Paediatrics and Adolescent Medicine, JMC-5704, The Juliane Marie Center, The University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark.

      E-mail: kjeld.schmiegelow@regionh.dk

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  • on behalf of the Nordic Society of Paediatric Haematology and Oncology (NOPHO)


  • Conflict of interest: Nothing to declare.

Abstract

Background

Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge.

Procedure

To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 (<5 leukocytes/µl CSF with blasts), CNS3 (≥5 leukocytes/µl with blasts or signs of CNS involvement), TLP+ (traumatic lumbar puncture with blasts), and TLP− (TLP with no blasts).

Results

Patients with CNS involvement had higher leukocyte count compared with patients with CNS1 (P < 0.002). Patients with CNS3 more often had T-ALL (P < 0.001) and t(9;22)(q34;q11)[BCR-ABL1] (P < 0.004) compared with patients with CNS1. Among patients with CNS involvement headache (17%) and vomiting (14%) were most common symptoms. Symptoms or clinical findings were present among 27 of 54 patients with CNS3 versus only 7 of 39 patients with CNS2 and 15 of 75 patients with TLP+ (P < 0.001). The majority of patients with CNS involvement received additional induction therapy. The post induction bone marrow residual disease level did not differ between patients with CNS involvement and patients with CNS1 (P > 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2).

Conclusion

CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. Pediatr Blood Cancer 2014; 61:1416–1421. © 2014 Wiley Periodicals, Inc.

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