strontium-radioisotopes and Leukemia--Radiation-Induced

Strontium-89 is a pure Beta-emitting radioactive analogue of calcium that has been shown to be beneficial in the palliation of pain due to osseous metastases from adenocarcinoma of the prostate. The most significant reported toxicity is dose-related, reversible, myelosuppression characterized primarily by thrombocytopenia.. A report of two patients in whom acute myelogenous leukemia (AML) developed after treatment with strontium-89 and a review of the literature are presented.. The two patients described in the current study developed AML 17 months and 26 months, respectively, after exposure to strontium-89 for the treatment of prostate carcinoma. To the authors' knowledge these patients represent the first two reported cases of AML after strontium-89 therapy for prostate carcinoma.. The results of the current study suggest the leukemogenic potential of strontium-89 treatment in humans. To the authors' knowledge, the current study represents the first report of AML after therapeutic exposure to strontium-89. As this agent is used more frequently (and earlier in the disease course) in patients with prostate carcinoma, an increased incidence of secondary AML complicating the clinical management of patients with prostate carcinoma may be observed. [See editorial on pages 497-9, this issue.]

Topics: Adenocarcinoma; Aged; Beta Particles; Bone Neoplasms; Dose-Response Relationship, Radiation; Fatal Outcome; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Neoplasms, Second Primary; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Strontium Radioisotopes; Thrombocytopenia

A 51-year-old woman diagnosed as having left breast cancer with axillary lymph node and liver metastases seven years earlier was seen in our office because of severe pancytopenia. She had received chemotherapy including several cycles of doxorubicin plus cyclophosphamide and docetaxel followed by hormone therapy containing leuprorelin and tamoxifen over four years. For management of bone pain due to metastasis, she had also undergone stereotaxic radiation therapy of the neck one and a half years earlier and unsealed internal radiation therapy with (89)Sr injection five months prior to the current presentation, Subsequently, myelosuppression progressively worsened and she finally required a blood transfusion. Although bone marrow examination showed severe hypoplasia, but neither blastic nor dysplastic, a test for PML-RARA fluorescence in situ hybridization was positive. After administration of all-trans retinoic acid, hematogenesis improved within three weeks. Neither disseminated intravascular coagulation nor retinoic acid syndrome was observed during the course of her illness. This is the first report describing acute promyelocytic leukemia after administration of (89)Sr, to our knowledge, and with an atypical onset and progression. As the number of cancer survivors increases due to improvements in medical intervention, clinicians must take more notice of special characteristics of therapy-related leukemia modified by previous treatments.

Topics: Breast Neoplasms; Combined Modality Therapy; Female; Humans; Iatrogenic Disease; Leukemia, Promyelocytic, Acute; Leukemia, Radiation-Induced; Middle Aged; Neoplasm Metastasis; Strontium Radioisotopes

Previous reports document a short latency of cancer onset in young children exposed to low doses of radioactivity. The standard mortality ratio (SMR) for cancer in children dying before age ten rose in the period 6-10 years after the Three Mile Island and Chernobyl accidents in populations most exposed to fallout. SMRs near most nuclear power plants were elevated 6-10 years after startup, particularly for leukemia. Cancer incidence in children under age ten living near New York and New Jersey nuclear plants increased 4-5 years after increases in average strontium-90 in baby teeth, and declined 4-5 years after Sr-90 averages dropped. The assumption that Sr-90 and childhood cancer are correlated is best supported for a supralinear dose-response, meaning the greatest per-dose risks are at the lowest doses. Findings document that the very young are especially susceptible to adverse effects of radiation exposure, even at relatively low doses.

Topics: Child; Child, Preschool; Environmental Exposure; Humans; Incidence; Infant; Infant, Newborn; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Nuclear Reactors; Pennsylvania; Power Plants; Proportional Hazards Models; Radiation Dosage; Radioactive Pollutants; Strontium Radioisotopes; Time Factors; Tooth, Deciduous; Ukraine; United States

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Humans; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Neoadjuvant Therapy; Neoplasms, Second Primary; Prostatic Neoplasms; Radiopharmaceuticals; Risk Factors; Strontium Radioisotopes

Topics: Acute Disease; Adolescent; Adult; Age Factors; Bone Neoplasms; Child; Child, Preschool; Cohort Studies; Environmental Exposure; Humans; Incidence; Infant; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Neoplasms; Nuclear Energy; Risk Factors; Scotland; Strontium Radioisotopes

Biochemical and morphological evidence indicates that a type-C retrovirus is present in the blood of swine (both leukemic and nonleukemic) exposed to strontium-90 radiation. Nonexposed swine that were leukemic also had virus present. The virus was shown to contain an RNase-sensitive DNA polymerase activity with cation, detergent and template requirements similar to those of known viral reverse transcriptases. The buoyant density of the virus was 1.14 to 1.16 g/ml, which can be converted, by treatment with ether, to a virion core having a density of 1.20 to 1.23 g/ml. Linear regression analysis indicated a correlation between virus-associated DNA polymerase activity and the number of blast cells in the peripheral blood.

Topics: Animals; Female; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Primary Myelofibrosis; Retroviridae; RNA-Directed DNA Polymerase; Strontium Radioisotopes; Swine; Swine, Miniature; Viral Proteins; Virus Activation

421 C57BL/6J female mice were subdivided into 11 groups. Five of these groups were given 300 rad total body irradiation from a 137Cs source at an age of 65 days. One day later, these irradiated mice were treated intraperitoneally with varying amounts of 90Sr (0, 0.032, 0.10, 0.32, and 1.0 mu Ci/g of body weight). Five groups of mice that had not been irradiated were treated on the same day with the same doses of 90Sr as given the five irradiated groups, and a sixth unirradiated group was treated with 2 mu Ci/g body weight. Each mouse treated with 90Sr and still alive was monitored between 249 and 303 days later in a total body well scintillation detector; mice with counts that differed by more than approximately 50% from the mean for their group were eliminated. A total of 402 mice were accepted for the experiment; these mice were followed to the end of their life span and then autopsied. Mice treated with the highest doses of 90Sr (1.0 and 2.0 mu Ci/g) experienced significantly elevated number of deaths from infections relative to the control group; these deaths occurred relatively early after 90Sr injection, and were particularly severe in the group of mice that had received 300 rad of external irradiation in addition to 1.0 mu Ci90Sr/g. There was no evidence of synergism between 90Sr injection and 300 rad external irradiation for production of bone tumors. Tumors of the type that occur spontaneously in C57BL/6J mice appeared to be more frequent in 90Sr-treated mice and in externally irradiated mice than in controls, but the numbers of excess tumors in these groups were not statistically significant (P less than 0.09).

Topics: Animals; Bone Neoplasms; Cesium Radioisotopes; Female; Infections; Injections, Intraperitoneal; Leukemia, Radiation-Induced; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasms, Radiation-Induced; Radiation Injuries, Experimental; Strontium Radioisotopes; Whole-Body Irradiation

Cloned cell lines were established from two swine with radiation-induced myeloproliferative disorders, including one cell culture from an animal with myelogenous leukemia and one from an animal with myeloid metaplasia. A third cloned cell line with similar morphology was established from pooled normal fetal swine cornea to compare the growth characteristics of cells from normal and irradiated swine. All three cell lines grew as foci of aggregated cells and were able to form macroscopic colonies in semisolid agar medium. The lack of normal mechanisms of contact inhibition and the observed aneuploidy indicated that these cells were morphologically transformed. Further, the cloned cells caused tumors in nude mice, clearly indicating that these cells were also malignantly transformed. A major difference between these cell lines was that type C viruses were observed only in the cells derived from swine with myeloproliferative disorders.

Topics: Animals; Cell Division; Cell Line; Cell Transformation, Neoplastic; Clone Cells; Cornea; Karyotyping; Leukemia, Myeloid; Leukemia, Radiation-Induced; Mice; Neoplasms, Experimental; Primary Myelofibrosis; Radiation Injuries, Experimental; Strontium Radioisotopes; Swine

Topics: Adult; Bone Neoplasms; Cesium Radioisotopes; Child; Humans; Indonesia; Iodine Radioisotopes; Leukemia, Radiation-Induced; Maximum Allowable Concentration; Neoplasms, Radiation-Induced; Radioactive Fallout; Strontium Radioisotopes

Single intraperitoneal doses of soluble 90Sr and monomeric 239Pu induced generalized lymphomatosis in laboratory mice. Leukaemogenesis due to soluble 226Ra was more uncertain. Clinical expression was variable, but as a generalization the disease was a lymphosarcoma with haematogenous (leukaemic) spread. Only rarely, unlike the commonly recorded forms of natural and X-ray-induced lymphosarcomas, was the thymus apparently the site of onset. The cell-type was lymphoblastic of undifferentiated null form (not T, not B). The average doses of alpha or beta radiation accumulated in the bone-marrow, the presumed site of induction, were at the time of diagnosis usually more than 2500 rad, but, if the cases occurring after radium or low activities of plutonium are accepted as induced, 300-1500 rad of alpha radiation. Mice converted to chimaeras only rarely exhibited any lymphoma, general or local. Abdominal lymphomas were not numerically increased by these radionucleides (perhaps due to shortening of life-span) though some may have been prematurely induced.

Topics: Animals; Chimera; Female; Leukemia, Experimental; Leukemia, Radiation-Induced; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Neoplasms, Experimental; Plutonium; Radium; Strontium Radioisotopes

Topics: Adenofibroma; Adenoma; Adrenal Gland Neoplasms; Animals; Cesium Isotopes; Female; Fibroma; Iodine Radioisotopes; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Mammary Neoplasms, Experimental; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Parathyroid Neoplasms; Radioisotopes; Rats; Strontium Radioisotopes; Thyroid Neoplasms

Topics: Adenoviridae; Animals; Cell Line; Cell Nucleus; Cell Transformation, Neoplastic; Culture Techniques; Cytopathogenic Effect, Viral; DNA Viruses; Inclusion Bodies, Viral; Kidney; Leukemia, Myeloid; Leukemia, Radiation-Induced; Microscopy, Electron; Retroviridae; Strontium Radioisotopes; Swine; Swine Diseases

Topics: Animals; Antibody Formation; Basophils; Bone Marrow; Hematopoietic Stem Cells; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma; Primary Myelofibrosis; Radiation Effects; Strontium Radioisotopes; Swine; Swine Diseases