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The Capital Region of Denmark - a part of Copenhagen University Hospital

Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience

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  1. Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Selection criteria for assembling a pediatric cancer predisposition syndrome gene panel

    Research output: Contribution to journalJournal articleResearchpeer-review

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The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10-3 at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10-3 . After a median follow-up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5-47·7) for MRD-positive versus 5·1% (95% CI: 1·3-19·2), P = 0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6-51·0, P = 0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4-97·2) and 67·4% (95% CI: 50·2-90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.

Original languageEnglish
JournalBritish Journal of Haematology
Issue number6
Pages (from-to)982-993
Publication statusPublished - Mar 2019

    Research areas

  • acute lymphoblastic leukaemia, children, haematopoietic stem cell transplantation, minimal residual disease

ID: 56427619