Bone sarcoma cumulative tumor rates in patients injected with 224Ra

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History and current uses of ²²⁴Ra in ankylosing spondylitis and other diseases.

During and briefly after World War II, 224Ra was used in a German hospital in combination with platinum and eosin (Peteosthor) for the treatment of tuberculosis and ankylosing spondylitis. The patients, primarily children and juveniles, received repeated intravenous injections of up to 2 MBq 224Ra per injection twice a week for months, sometimes even for years. Injected amounts totalled up to 140 MBq. Following this therapy, an enormous increase in the incidence of bone tumors (56 cases among 900 patients), as well as other lesions was observed. The surviving patients are still under follow-up. Treatment of ankylosing spondylitis with drastically reduced doses of 224Ra, however, was continued up to the recent present and over 1500 patients were so treated in West-German hospitals. This second cohort, exclusively adults, received much lower amounts applied in most cases as one series of 10 weekly injections of about 1 MBq of 224Ra each. This would result in a cumulative alpha-dose of about 0.56 Gy to the marrow-free skeleton of a 70 kg man. These patients have been followed for several years, together with a control group of ankylosing spondylitis patients not treated with radioactive drugs or x-rays. By August 1991, three cases of malignant bone tumors have been observed among the exposed (0.7 - 2.4 cases expected) vs. one case among the controls. Diseases of hematopoietic tissue included leukemias (9 in the exposure group vs. 6 in the control group) and bone marrow failure (12 cases vs. 9). The increase of total leukemias among the exposed, compared to a standard population, is highly significant (9 cases observed vs. 2.8 expected, p < 0.003). Chronic myeloid leukemia, specifically, was elevated in the exposed group (3 cases observed vs. 0.8 expected, p = 0.047) but not in the control group