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

Abstract

We performed an epidemiological study on 1,471 ankylosing spondylitis patients treated with repeated intravenous injections of the short lived alpha-emitter (224)Ra (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 (224)Ra.

Absorbed Doses and Risk Estimates of 211At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

“…The only long-term follow-up of an alpha-particle therapy involved 224 Ra against ankylosing spondylitis which revealed a higher frequency of leukaemia [32]. When combined with dose estimates [12], one can derive that the risk for some absorbed dose from alphas is about seven times higher than for low-LET M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 14 irradiation.…”

Antitumor Activity of Novel Bone-seeking, α-emitting 224Ra-solution in a Breast Cancer Skeletal Metastases Model

“…Previously, 224 Ra without EDTMP was used in treatment of ankylosing spondylitis (6)(7)(8). Long-term toxicity and carcinogenicity data in humans exist from this usage (6,(19)(20)(21)(22)(23)(24) indicating a quite acceptable safety profile compared with other cancer therapeutics, and could possibly be further improved upon by adding EDTMP for soft tissue protection and by using a more moderate dosing intensity. Our data demonstrate for the first time that a single treatment with 224 Ra-solution resulted in a significant prolongation of symptom-free survival, reduction of paraplegia induction and decreased number and areas of bone metastases.…”

“…Injected amounts were up to 140 MBq 224 Ra (7). Such high cumulative doses of 224 Ra led to increased incidences of myeloid leukemia and malignancies of bones, kidneys and thyroid, and 224 Ra was abandoned since 1990 (6,22). An elevated risk for malignant bone tumors, however, has not been proven after low-dose treatment with 10 MBq 224 Ra (6).…”

Effects of Low-Dose Radon Therapy Applied Under Hyperthermic Conditions (RnHT) on Inflammatory and Non- Inflammatory Degenerative Disease Conditions

“…In 2000 it was reapproved in Germany by the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte) as a pharmaceutical product for patients suffering from ankylosing spondylitis with stage II and III spinal ossification, provided that other therapy options had either failed or been contraindicated. However, recent findings clearly demonstrated an increased incidence of leukaemia and other malignant diseases in patients that were treated between 1948 and 1975 [6]. Despite the analgesic effects elicited by 224 Radiumchloride-injections, the risk for malignant diseases exceeds the benefit and therefore, the committee for quality assurance of the German Society for Rheumatology no longer recommends this kind of therapy.…”

“…Until now several studies have been conducted with a reduced dose regimen of 10 weekly injections with 1 MBq each resulting in an effective dose of 2.5 Sv [5] and a cumulative bone dose of 0.6 Gy [6]. The short-lived 224 Radium has a half-life of 3.6 days and preferentially accumulates in the bone and in recently formed tissue calcifications when introduced into the body.…”