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Leukaemia and myeloid malignancy among people exposed to low doses (<100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies

Lookup NU author(s): Dr David Campbell, Professor Mark PearceORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Background Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly inchildhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv)radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimatethe risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years).Methods In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014. Weevaluated leukaemia and myeloid malignancy outcomes in these cohorts with the relevant InternationalClassification of Diseases and International Classification of Diseases for Oncology definitions. The cohortsincluded had not been treated for malignant disease, had reported at least five cases of the relevant haematopoieticneoplasms, and estimated individual active bone marrow (ABM) doses. We restricted analysis to individuals whowere younger than 21 years at first irradiation who had mean cumulative ABM doses of less than 100 mSv.Dose-response models were fitted by use of Poisson regression. The data were received in fully anonymised formby the statistical analyst.Findings We identified nine eligible cohorts from Canada, France, Japan, Sweden, the UK, and the USA, including262 573 people who had been exposed to less than 100 mSv enrolled between June 4, 1915, and Dec 31, 2004. Meanfollow-up was 19·63 years (SD 17·75) and mean cumulative ABM dose was 19·6 mSv (SD 22·7). 154 myeloidmalignancies were identified (which included 79 acute myeloid leukaemias, eight myelodysplastic syndromes, and36 chronic myeloid leukaemias, in addition to other unspecified myeloid malignancies) and 40 acute lymphoblasticleukaemias, with 221 leukaemias (including otherwise unclassified leukaemias but excluding chronic lymphocyticleukaemia) identified overall. The fitted relative risks at 100 mSv were 3·09 (95% CI 1·41–5·92; ptrend=0·008) foracute myeloid leukaemia and myelodysplastic syndromes combined, 2·56 (1·09–5·06; ptrend=0·033) foracute myeloid leukaemia, and 5·66 (1·35–19·71; ptrend=0·023) for acute lymphoblastic leukaemia. There was noclear dose-response for chronic myeloid leukaemia, which had a relative risk at 100 mSv of 0·36 (0·00–2·36;ptrend=0·394). There were few indications of between-cohort heterogeneity or departure from linearity. For acutemyeloid leukaemia and myelodysplastic syndromes combined and for acute lymphoblastic leukaemia, the doseresponsesremained significant for doses of less than 50 mSv. Excess absolute risks at 100 mSv were in the rangeof 0·1–0·4 cases or deaths per 10 000 person-years.Interpretation The risks of acute myeloid leukaemia and acute lymphoblastic leukaemia were significantly increasedafter cumulative doses of ionising radiation of less than 100 mSv in childhood or adolescence, with an excess risk alsoapparent for cumulative radiation doses of less than 50 mSv for some endpoints. These findings support an increasedrisk of leukaemia associated with low-dose exposure to radiation and imply that the current system of radiologicalprotection is prudent and not overly protective.

Publication metadata

Author(s): Little MP, Wakeford R, Borrego D, French B, Zablotska L, Adams JM, Allodji R, deVathaire F, Lee C, Brenner AV, Miller JS, Campbell D, Pearce MS, Doody MM, Holmberg E, Lundell M, Sadetzki S, Linet MS, BerringtondeGonzalez A

Publication type: Article

Publication status: Published

Journal: The Lancet Haematology

Year: 2018

Volume: 5

Issue: 8

Pages: e346-e358

Print publication date: 01/08/2018

Online publication date: 17/07/2018

Acceptance date: 02/04/2018

Date deposited: 17/07/2018

ISSN (electronic): 2352-3026

Publisher: The Lancet Publishing Group


DOI: 10.1016/S2352-3026(18)30092-9


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Funder referenceFunder name
National Cancer Institute