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Incidence of leukaemia and other malignant diseases following injections of the short-lived α-emitter 224Ra into man

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Abstract

We performed an epidemiological study on 1,471 ankylosing spondylitis patients treated with repeated intravenous injections of the short lived α-emitter 224Ra (excluding radiation therapy with X-rays) between 1948 and 1975. These patients have been followed together with a control group of 1,324 ankylosing spondylitis patients treated neither with radioactive drugs nor with X-rays. The mean follow-up time was 26.3 years in the exposed and 24.6 years in the control group. To date, causes of death have been ascertained for 1,006 exposed patients and 1,072 controls. Special emphasis was placed on the reporting of malignant diseases. Expected numbers of cases were computed for the age, sex and calendar year distribution of both groups using cancer registry incidence rates. In the exposed group 18 cases of kidney cancer (vs. 9.1 cases expected, P < 0.01) and 4 malignant thyroid tumours (vs. 1.2 cases expected, P = 0.03) were observed. In the control group the observed cases for these tumours were not significantly elevated. The most striking observation, however, were the 21 cases of leukaemia in the exposed 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 sub-classification of the leukaemias demonstrated a high increase of myeloid leukaemia in the exposed group (12 cases observed vs. 2.9 cases expected, P < 0.001), and out of these, especially a high excess of acute myeloid leukaemias (7 cases observed vs. 1.8 expected, P = 0.003). In the controls the observed cases are within the expected range (4 myeloid leukaemias vs. 3.1 cases). This increase in total leukaemias as well as particularly in myeloid leukaemias is significant in direct comparison between the exposed and control groups too (P < 0.05). The enhanced leukaemia incidence in the exposed group is in line with the observation of increased leukaemia incidence in mice injected with 224Ra.

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References

  • Abel U (2003) Gutachten zum Stand des Nachweises der Wirksamkeit einer Radontherapie aufgrund klinischer Studien. In: Bühring M, Kemper FH (eds) Naturheilverfahren und unkonventionelle medizinische Richtungen. Springer, Berlin, pp 1–8

    Google Scholar 

  • Alberding A, Stierle H, Brandt J, Braun J (2006) Wirksamkeit und Verträglichkeit von Radiumchlorid in der Behandlung der ankylosierenden Spondylitis—Ergebnisse einer Anwendungsbeobachtung. Z Rheumatol 65:245–251

    Article  Google Scholar 

  • Askling J, Klareskog L, Blomqvist P, Fored M, Feltelius N (2006) Risk for malignant lymphoma in ankylosing spondylitis: a nationwide Swedish case-control study. Ann Rheum Dis 65:1184–1187

    Article  Google Scholar 

  • Bergter W, Gilbert M, Fitschen J (2003) Prinzip einer spezifischen Entzündungshemmung und Schmerzlinderung mit [224Ra]Radiumchlorid. Osteoporose Rheuma aktuell:6–19

    Google Scholar 

  • Braun J, Pincus T (2002) Mortality, course of disease and prognosis of patients with ankylosing spondylitis. Clin Exp Rheumatol 20:S16–S22

    Google Scholar 

  • Braun J, Lemmel EM, Manger B, Rau R, Sörensen H, Sieper J (2001) Therapie der ankylosierenden Spondylitis (AS) mit Radiumchlorid (224SpondylAT®). Z Rheumatol 60:74–83

    Article  Google Scholar 

  • Chmelevsky D, Kellerer AM, Land CE, Mays CW, Spiess H (1988) Time and dose dependency of bone-sarcomas in patients injected with Radium-224. Radiat Environ Biophys 27:103–114

    Article  Google Scholar 

  • Darby SC, Doll R, Gill SK, Smith PG (1987) Long term mortality after a single treatment course with X-rays in patients treated for ankylosing spondylitis. Br J Cancer 55:179–190

    Google Scholar 

  • Delikan O (1978) Quality control in the production process and purity of 224Ra for injection. In: Müller WA, Ebert HG (eds) Biological effects of 224Ra—benefit and risk of therapeutic application. Martinus Nijhoff Medical Division, The Hague/Boston, pp 44–49

    Google Scholar 

  • Franke A, Reiner L, Pratzel HG, Franke T, Resch KL (2000) Long-term efficacy of radon spa therapy in rheumatoid arthritis—a randomized, sham-controlled study and follow-up. Rheumatology (Oxford) 39:894–902

    Article  Google Scholar 

  • Gössner W, Wick RR, Spiess H (1995) Histopathological review of 224Ra-induced bone sarcomas. In: van Kaick G, Karaoglou A, Kellerer AM (eds) Health effects of internally deposited radionuclides: emphasis on radium and thorium. World Scientific, Singapore, pp 255–259

    Google Scholar 

  • Humphreys ER, Loutit JF, Major IR, Stones VA (1985) The induction by 224Ra of myeloid leukaemia and osteosarcoma in male CBA mice. Int J Radiat Biol 47:239–247

    Google Scholar 

  • Humphreys ER, Loutit JF, Stones VA (1987) The induction by 239Pu of myeloid leukaemia and osteosarcoma in female CBA mice. Int J Radiat Biol 51:331–339

    Article  Google Scholar 

  • Humphreys ER, Isaacs KR, Raine TA, Saunders J, Stones VA, Wood DL (1993) Myeloid leukaemia and osteosarcoma in CBA/H mice given 224Ra. Int J Radiat Biol 64:231–235

    Article  Google Scholar 

  • Jimenez-Balderas FJ, Mintz G (1993) Ankylosing spondylitis: clinical course in women and men. J Rheumatol 20:2069–2072

    Google Scholar 

  • Koch W, Reske W (1952) Die Ergebnisse der intravenösen Thorium X-Behandlung bei der Spondylarthritis ankylopoetica (M. Bechterew). Strahlenther 87:439–457

    Google Scholar 

  • Kutz G (1963) Zur Frage von Spätschäden nach der Behandlung mit Thorium-X. Z Orthop 97:474–482

    Google Scholar 

  • Leggett RW (1992) A generic age-specific biokinetic model for Calcium-like elements. Radiat Prot Dosimetry 41:183–198

    Google Scholar 

  • Moskalev YI, Streltsova VN, Buldakov LA (1969) Late effects of radionuclide damage. In: Mays CW, Jee WSS, Lloyd RD, Stover BJ, Dougherty JH, Taylor GN (eds) Delayed effects of bone-seeking radionuclides. University of Utah Press, Salt Lake City, pp 489–509

    Google Scholar 

  • Müller WA, Linzner U, Luz A (1988) Early induction of leukemia (malignant lymphoma) in mice by protracted low alpha doses. Health Phys 54:461–463

    Google Scholar 

  • Müller WA, Luz A, Murray AB, Linzner U (1989) The effect of dose protraction with a very low Radium-224 activity in mice. In: Taylor DM, Mays CW, Gerber GB, Thomas RG (eds) Risks from radium and thorotrast, BIR Report 21. British Institute of Radiology, London, pp 32–36

  • Nagy K, Berhés I, Kovács T, Kávási N, Somlai J, Bender T (2009) Does balneotherapy with low radon concentration in water influence the endocrine system? A controlled non-randomized pilot study. Radiat Environ Biophys. doi:10.1007/s00411-009-0222-3

  • Nekolla EA, Kellerer AM, Kuse-Isingschulte M, Eder E, Spiess H (1999) Malignancies in patients treated with high doses of Radium-224. Radiat Res 152:S3–S7

    Article  Google Scholar 

  • Nekolla EA, Kreisheimer M, Kellerer AM, Kuse-Isingschulte M, Gössner W, Spiess H (2000) Induction of malignant bone tumors in Radium-224 patients: risk estimates based on the improved dosimetry. Radiat Res 153:93–103; Erratum 153:848

    Google Scholar 

  • Reiners C (2000) Gutachterliche Stellungnahme zu [224Ra]Radiumchlorid: Pharmakokinetik/Strahlenexposition vom 14.02.2000. Klinik und Poliklinik der Nuklearmedizin, Universität Würzburg (cited from Braun et al. (2001), Ref. 27, p. 75)

  • Schales F (1966) Biophysikalische Untersuchungen über die Verteilung und Ausscheidung von Thorium X (Ra-224) und seinen Folgeprodukten nach intravenöser Zufuhr beim Menschen. Thesis, Johann-Wolfgang-Goethe-Universität, Frankfurt/Main

  • Schales F (1978) Brief history of 224Ra usage in radiotherapy and radiobiology. Health Phys 35:25–32

    Article  Google Scholar 

  • Schales F, Jones DEA (1970) The specification of thorium X activity—the e. s. u. to curie conversion. Brit J Radiol 43:471–478

    Article  Google Scholar 

  • Spiess H (2002) Peteosthor—a medical disaster due to Radium-224. Radiat Environ Biophys 41:163–172

    Google Scholar 

  • Spiess H, Mays CW (1970) Bone cancers induced by 224Ra (Th X) in children and adults. Health Phys 19:713–729; Addendum Health Phys 20:543–545 (1971)

    Google Scholar 

  • Stieglitz R, Thiele M, Stobbe H, Wegener G (1973) Schädigungen der Hämatopoese durch Thorium-X-Therapie. Folia Haematol (Leipzig) 100:95–103

    Google Scholar 

  • Straube F, Sagner K, Brandt J, Riede D, Tutar K, Mende T (2003) Martin-Luther-Universität Halle-Wittenberg: 40 Jahre Erfahrung mit [224Ra]Radiumchlorid bei ankylosierender Spondylitis. Osteoporose Rheuma aktuell 26–29

  • Svoboda V, Bubeníková D, Kotašková Z (1981) Myeloid leukemia 239Pu-treated mice. J Cancer Res Clin Oncol 100:255–262

    Article  Google Scholar 

  • Troch P (1949) Peteosthor: Neue Wege des Heilens. Vieweg, Braunschweig

    Google Scholar 

  • van Kaick G, Wesch H (2005) The national Thorotrast studies in comparison. In: Oeh U, Roth P, Paretzke HG (eds) Health effects of incorporated radionuclides—emphasis on radium, thorium, uranium and their daughter products—HEIR 2004. GSF, Neuherberg, GSF-Bericht 06/05, pp 17–20

  • van Kaick G, Dahlheimer R, Hornik S, Kaul A, Liebermann D, Lührs H, Spiethoff A, Wegener K, Wesch H (1999) The German Thorotrast study: recent results and assessment of risks. Radiat Res 152:S64–S71

    Article  Google Scholar 

  • van Tubergen A, Landewé R, van der Heijde D, Hidding A, Wolter N, Asscher M, Falkenbach A, Genth E, Thè HG, van der Linden S (2001) Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial. Arthritis Rheum 45:430–438

    Article  Google Scholar 

  • Wick RR, Gössner W (1983) Follow-up study of late effects in 224Ra treated ankylosing spondylitis patients. Health Phys 44(Suppl 1):187–195

    Google Scholar 

  • Wick RR, Gössner W (1993) History and current uses of 224Ra in ankylosing spondylitis and other diseases. Environm Intern 19:467–473

    Article  Google Scholar 

  • Wick RR, Nekolla EA (2005) Long term investigation of late effects in ankylosing spondylitis patients treated with Radium-224. In: Oeh U, Roth P, Paretzke HG (eds) Health effects of incorporated radionuclides—emphasis on radium, thorium, uranium and their daughter products—HEIR 2004. GSF, Neuherberg, GSF-Bericht 06/05, pp 75–81

  • Wick RR, Müller WA, Linzner U (1983) Distribution studies in mice of 224Ra in colloidal (“Peteosthor”) and ionic preparations as used in human therapy. Health Phys 44:580–583

    Google Scholar 

  • Wick RR, Chmelevsky D, Gössner W (1985) 224Ra: risk to bone and haematopoietic tissue in ankylosing spondylitis patients. Strahlenther [Sonderb] 80:38–44

    Google Scholar 

  • Wick RR, Nekolla EA, Gössner W, Kellerer AM (1999) Late effects in ankylosing spondylitis patients treated with 224Ra. Radiat Res 152:S8–S11

    Article  Google Scholar 

  • Wolf PM, Born H-J (1941) Über den Reinheitsgrad von Thorium X-Präparaten. Strahlenther 70:349–351

    Google Scholar 

  • Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JC Jr, Dijkmans B, Dougados M, Geher P, Inman RD, Khan MA, Kvien TK, Leirisalo-Repo M, Olivieri I, Pavelka K, Sieper J, Stucki G, Sturrock RD, van der Linden S, Wendling D, Bohm H, van Royen BJ, Braun J (2006) ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 65:442–452

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by the “Bundesministerium für Umwelt, Naturschutz und Reaktorsicherheit”, BMU (Project StSch 4401 of the “Bundesamt für Strahlenschutz”, BfS).

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Correspondence to E. A. Nekolla.

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Wick, R.R., Atkinson, M.J. & Nekolla, E.A. Incidence of leukaemia and other malignant diseases following injections of the short-lived α-emitter 224Ra into man. Radiat Environ Biophys 48, 287–294 (2009). https://doi.org/10.1007/s00411-009-0227-y

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