thorium-x and Leukemia--Radiation-Induced

Up to the end of World War II, there was no effective therapy against bone tuberculosis, and even today there is no treatment for ankylosing spondylitis. However, in the 1940s up to about 1956, radiotherapy with "Peteosthor" - a drug containing Thorium X ((224)Ra) as an effective compound - was introduced in Germany as a presumed cure and it maintained a central place in the treatment of these diseases. In 1948, I was entrusted to assess the new treatment. Animal studies and the clinical evaluation of the patients made me soon realise a number of severe adverse health effects which induced me to pronounce and subsequently repeat warnings against the intravenous administration of high doses of (224)Ra, especially because it was then administered predominantly to children and juveniles. As a consequence, this type of treatment was finally abandoned in 1956. But there remained a need to observe and document the resulting late health effects. Already in 1967, our initial follow-up study provided data for about 800 patients with exact information on the (224)Ra dose levels administered, administration schemes, and the resulting detrimental effects. A large number of bone sarcomas was the most severe consequence, but even today there is a broad spectrum of other grave health effects. A summary of the major scientific insights which have been achieved in the course of the still on-going epidemiological studies is part of this report.

Topics: Aged; Female; Follow-Up Studies; Germany; Humans; Leukemia, Radiation-Induced; Male; Middle Aged; Neoplasms, Radiation-Induced; Radiation Injuries; Radiopharmaceuticals; Radiotherapy Dosage; Radium; Spondylitis, Ankylosing; Thorium; Time Factors; Tuberculosis, Osteoarticular

To investigate long-term health effects in AS patients treated with (224)Ra.. A prospective epidemiological study has been carried out on 1471 AS patients treated with repeated intravenous injections of (224)Ra 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.. 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).. 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 alpha-emitter (224)Ra. In these studies, in animals exposed to lower doses of (224)Ra, i.e. at doses lower than those found to induce osteosarcomas, an increased risk of leukaemia was observed.

Topics: Adult; Aged; Aged, 80 and over; Denmark; Epidemiologic Methods; Female; Germany; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Middle Aged; Radium; Spondylitis, Ankylosing; Thorium

Topics: Bone Neoplasms; Female; Follow-Up Studies; Germany, West; Humans; Leukemia, Radiation-Induced; Male; Neoplasms, Radiation-Induced; Radiation Dosage; Radium; Risk; Spondylitis, Ankylosing; Thorium; Time Factors

Topics: Animals; Dose-Response Relationship, Radiation; Femur; Hematopoietic Stem Cells; Leukemia, Radiation-Induced; Male; Mice; Mice, Inbred CBA; Radium; Thorium

Topics: Adult; Humans; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Radiation Injuries; Radium; Spondylitis, Ankylosing; Thorium