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Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation

Leukemia volume 14, pages 2267–2275 (2000)Cite this article

Abstract

In this population-based material from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2860 children below 15 years of age were diagnosed with acute lymphoblastic leukemia (ALL) from July 1981 to June 1998. The annual incidence was 3.9/100 000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification with multidrug chemotherapy, including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. The overall event-free survival (EFS) at 5 years has increased from 56.5 ± 1.7% in the early 1980s to 77.6 ± 1.4% during the 1990s. The main improvements were seen in children with non-high risk leukemia. In high-risk patients, progress has been moderate, especially in children with high WBC (⩾100 × 109/l) at diagnosis. During the last time period (January 1992–June 1998), only 10% of the patients have received cranial irradiation in first remission, while 90% of the patients have received pulses of high dose methotrexate (5–8 g/m2) isolated or combined with high-dose cytosine arabinoside (total dose 12 g/m2) plus multiple intrathecal injections of methotrexate as CNS-targeted treatment, not translating into increased cumulative incidence of CNS relapse.

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Acknowledgements

Financial support was received from the Swedish Child Cancer Foundation and the Cancer Foundations in Denmark, Norway and Finland.

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Authors and Affiliations

  1. Childhood Cancer Research Unit, Karolinska Institute, Stockholm, Sweden

    G Gustafsson

  2. Department of Pediatrics, The Juliane Marie Center, Rigshospitalet Copenhagen, Denmark

    K Schmiegelow

  3. Department of Pediatrics, University Hospital, Umeå, Sweden

    E Forestier

  4. Department of Pediatrics, University Hospital, Skejby Hospital Aarhus, Denmark

    N Clausen

  5. Department of Pediatrics, National Hospital, Oslo, Norway

    A Glomstein

  6. Department of Pediatrics, University Hospital, Reykjavik, Iceland

    G Jonmundsson

  7. Department of Pediatrics, University Hospital, Queen Sylvia's Children Hospital, Gothenburg, Sweden

    L Mellander

  8. Department of Pediatrics, University Hospital, Tampere, Finland

    A Mäkipernaa

  9. Department of Pediatrics, University Hospital, Trondheim, Norway

    R Nygaard

  10. Department of Pediatrics, University Hospital, Kuopio, Finland

    UM Saarinen-Pihkala

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  1. G Gustafsson
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  2. K Schmiegelow
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  4. N Clausen
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  5. A Glomstein
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  6. G Jonmundsson
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  7. L Mellander
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  8. A Mäkipernaa
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  9. R Nygaard
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  10. UM Saarinen-Pihkala
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on behalf of the Nordic Society of Pediatric Haematology and Oncology (NOPHO)

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Gustafsson, G., Schmiegelow, K., Forestier, E. et al. Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation. Leukemia 14, 2267–2275 (2000). https://doi.org/10.1038/sj.leu.2401961

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