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Acute Leukemias

Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia

Leukemia volume 27, pages 866–870 (2013)Cite this article

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Abstract

Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL92 or the NOPHO ALL2000 protocols between 1992 and 2007. The 5-year event-free survival probability (pEFS5 yr) for the 66 DS patients was inferior to the 2602 non-DS patients (0.50±0.07 vs 0.77±0.01 (P<0.001)). The 48 DS patients in first remission at the beginning of maintenance therapy had pEFS10 yr below that of the 522 non-DS control patients (pEFS10 yr: 0.58 (95% confidence interval (CI) 0.43–0.77) vs 0.83 (95% CI 0.80–0.86), respectively (P<0.0001)). The DS patients received lower median doses of MTX (median: 11.8 vs 15.4 (P<0.0001)) and 6MP (median: 43.6 vs 59.4 (P<0.0001)). In Cox regression analysis, male gender, presence of DS and high median maintenance therapy white blood cell levels (mWBC) were associated with increased risk for relapse. DS-ALL patients with mWBC above or below 3.5 × 109/l (protocol target) had pEFS10 yr of 0.31 and 0.72 (P=0.02), and the mWBC hazard ratio for DS-ALL patients was 2.0 (P<0.0005). We conclude that insufficient treatment intensity during maintenance therapy of DS-ALL patients may contribute to their poor prognosis.

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Acknowledgements

This study has received financial support from: The Danish Cancer Society (Grant nos: 91-048, 92-017, 93-017, 95-100-28, R19-A984), The Otto Christensen Foundation, The Swedish Childhood Cancer Foundation (Grant nos. 53/91, 62/94, 72/96, 98/59), The Lundbeck Foundation (Grant no. 38/99) and The Danish Childhood Cancer Foundation.

Author contributions

CB designed the study, collected data, analyzed data and drafted the paper; ML drafted the paper; SR analyzed data; BZ collected data; MT collected data; SH collected data; HB collected data; MH collected data; and KS designed the study, collected data, analyzed data and drafted the paper. All authors approved the final manuscript.

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Authors and Affiliations

  1. Pediatrics and Adolescent Medicine, The Juliane Marie Centre, The University Hospital Rigshospitalet, Copenhagen, Denmark

    C Bohnstedt, M Levinsen & K Schmiegelow

  2. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

    S Rosthøj

  3. Department of Pediatrics, University Hospital, Oslo, Norway

    B Zeller

  4. Children’s Hospital, Helsinki University Hospital, Helsinki, Finland

    M Taskinen

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

    S Hafsteinsdottir

  6. Department of Women’s and Children’s Health, Childhood Cancer Research Unit, Karolinska Institute, Stockholm, Sweden

    H Björgvinsdóttir & M Heyman

  7. The Institute of Gynecology, Obstetrics and Pediatrics, The Faculty of Health Sciences, The University of Copenhagen, Copenhagen, Denmark

    K Schmiegelow

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Correspondence to K Schmiegelow.

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Bohnstedt, C., Levinsen, M., Rosthøj, S. et al. Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia. Leukemia 27, 866–870 (2013). https://doi.org/10.1038/leu.2012.325

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