Rheumatology Advance Access published online on April 4, 2008
Rheumatology, doi:10.1093/rheumatology/ken060
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Increased risk of myeloid leukaemia in patients with ankylosing spondylitis following treatment with radium-224
1GSF—National Research Center for Environment and Health, Institute of Radiobiology, 2Federal Office for Radiation Protection, Department of Radiation Protection and Health, Neuherberg, 3Department of Rheumatology and 4Department of Orthopaedics, University Hospital Münster, Münster, Germany.
Correspondence to:
R. R. Wick, GSF—National Research Center for Environment and Health, Institute of Radiobiology, Ingolstädter Landstr. 1, PO Box 1129, D-85758 Neuherberg. E-mail: wick{at}gsf.de
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Abstract |
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Objective. To investigate long-term health effects in AS patients treated with 224Ra.
Methods. A prospective epidemiological study has been carried out on 1471 AS patients treated with repeated intravenous injections of 224Ra between 1948 and 1975. These patients have been followed together with a control group of 1324 AS patients not treated with radioactive drugs and/or X-rays. Numbers of malignancies expected in a normal population were computed from German and Danish cancer registry data.
Results. After a mean follow-up time of 26 yrs in the exposed group or 25 yrs in the control group, causes of death have been ascertained for 1006 exposed patients and 1072 controls. In particular, 19 cases of leukaemia were observed in the exposure group (vs 6.8 cases expected, P < 0.001) compared to 12 cases of leukaemia in the control group (vs 7.5 cases expected). Further subclassification of the leukaemia cases demonstrated a high increase of myeloid leukaemia in the exposure group (11 cases observed vs 2.9 cases expected, P < 0.001), especially a high excess of acute myeloid leukaemias (7 cases observed vs 1.8 cases expected, P = 0.003), whereas in the controls the observed cases are within the expected range (4 myeloid leukaemias vs 3.1 cases expected).
Conclusions. The enhanced leukaemia incidence in the exposed group is in line with results from experiments in mice injected with varying amounts of the bone-seeking 
-emitter 224Ra. In these studies, in animals exposed to lower doses of 224Ra, i.e. at doses lower than those found to induce osteosarcomas, an increased risk of leukaemia was observed.
KEY WORDS: Ankylosing spondylitis, Radium-224, Radiopharmaceutical, Late effects, Radiation risk, Malignant disease, Myeloid leukaemia, Follow-up study, Humans, Adult
Submitted 28 September 2007;
revised version accepted 25 January 2008.
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