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Br J Haematol. 2019 Mar;184(6):982-993. doi: 10.1111/bjh.15761. Epub 2019 Jan 24.

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

Author information

1
Department of Paediatric and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
2
Lund University Hospital, Lund, Sweden.
3
The Tissue Typing Laboratory, Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
4
Astrid Lindgren Children's Hospital and Clintec, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
5
Department of Paediatric Haematology and Oncology, Oslo University Hospital, Oslo, Norway.
6
Institution for Clinical Sciences, Department of Paediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden.
7
Uppsala University Children's Hospital, Uppsala, Sweden.
8
Centre for Paediatric Oncology and Haematology, Children's Hospital, Vilnius University Hospital, Vilnius, Lithuania.
9
Tallin Children's Hospital, Tallin, Estonia.
10
Department of Paediatrics, St. Olavs University Hospital Trondheim, Trondheim, Norway.
11
Department of Clinical and Molecular Medicine, NTNU, Trondheim, Norway.
12
Landspitali University Hospital, Reykjavik, Iceland.
13
Childhood Cancer Research Unit, Karolinska Institute, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
14
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
15
Department of Paediatrics, University of Helsinki, Helsinki, Finland.

Abstract

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.

KEYWORDS:

acute lymphoblastic leukaemia; children; haematopoietic stem cell transplantation; minimal residual disease

PMID:
30680711
DOI:
10.1111/bjh.15761

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