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Acute Leukemias

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

Leukemia volume 24, pages 715–720 (2010)Cite this article

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Abstract

Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (⩾10 years) and 176 non-adolescents (<10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) <50 × 109/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS12y:0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (rS=0.36, P=0.02), which became nonsignificant for those who relapsed (rS=0.05, P=0.9). The best-fit multivariate Cox regression model to predict risk of relapse included mWBC and thiopurine methyltransferase activity, which methylates mercaptopurine and reduces the intracellular availability of cytotoxic 6-thioguanine nucleotides (coefficient: 0.11, P=0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient=0.65, P=0.003) than for non-adolescents (coefficient=0.42, P=0.04). Adolescents had higher mean neutrophil counts (P=0.002) than non-adolescents, but received nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy. Red blood cell MTX levels were significantly related to the dose of MTX among adolescents who stayed in remission (rS=0.38, P=0.02), which was not the case for those who developed a relapse (rS=0.15, P=0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.

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Acknowledgements

This study has received financial support from The Danish Childhood Cancer Foundation, The Carl and Ellen Hertz Foundation, The Children's Cancer Foundation of Sweden (grant no.: 53/91, 62/94, 72/96, 98/59), The Danish Cancer Society (grant no.: 91-048, 92-017, 93-017, 95-100-28), The JPC Foundation, The Lundbeck Foundation (grant no.: 38/99), The Minister Erna Hamilton Foundation, The Nordic Cancer Union (grant no.: 56-9257, 56-100-03-9102). Kjeld Schmiegelow holds the Danish Childhood Cancer Foundation Professorship in Pediatric Oncology.

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Authors and Affiliations

  1. Department of Pediatric Oncology, The University Hospital Rigshospitalet, Copenhagen, Denmark

    K Schmiegelow & B Lausen

  2. Faculty of Medicine, Institute of Gynecology, Obstetrics and Pediatrics, University of Copenhagen, Copenhagen, Denmark

    K Schmiegelow

  3. Department of Pediatric Oncology, Astrid Lindgrens Barnsjukhus, Stockholm, Sweden

    M Heyman & G Gustafsson

  4. Department of Pediatric Oncology, The National University Hospital Rikshospitalet, Oslo, Norway

    F Wesenberg

  5. Department of Pediatric Oncology, The National Hospital, Reykjavik, Iceland

    J Kristinsson

  6. Department of Pediatric Oncology, The University Hospital, Tampere, Finland

    K Vettenranta

  7. Department of Pediatric Oncology, Århus University Hospital, Skejby, Denmark

    H Schroeder

  8. Department of Pediatric Oncology, Umeå University Hospital, Ume, å, Sweden

    E Forestier

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

    S Rosthoej

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Schmiegelow, K., Heyman, M., Gustafsson, G. et al. The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse. Leukemia 24, 715–720 (2010). https://doi.org/10.1038/leu.2009.303

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