strontium-radioisotopes and Thrombocytopenia

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

Topics: Antibodies, Monoclonal; Ascites; Bone Neoplasms; Chromium Compounds; Humans; Hyperthyroidism; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Organometallic Compounds; Organophosphorus Compounds; Pain; Patient Isolation; Phosphates; Pleural Effusion, Malignant; Polycythemia Vera; Radiation Protection; Radiopharmaceuticals; Sodium Iodide; Strontium Radioisotopes; Thrombocytopenia; Thyroid Neoplasms; Yttrium Radioisotopes

Strontium-89 (Sr-89) chloride is an effective palliative treatment of the bone metastases of prostate cancer. Chemotherapy has also been shown to have a palliative benefit in this disease. We aimed to determine the benefits and complications of Sr-89 therapy in patients with prostate cancer who had become refractory to chemotherapy. We conducted a retrospective review of 14 treatments administered to 13 patients with chemotherapy-resistant and hormone-resistant prostate cancer.. Of the 14 administered treatments, 8 (57%) resulted in improved pain control, with 2 patients able to stop analgesia. The median duration of response was 56 days. No prostate-specific antigen response was seen in the 8 patients tested. There was significant and prolonged bone marrow toxicity, with 6 patients requiring red blood cell transfusion. Prolonged thrombocytopenia was seen, with platelet counts remaining below baseline levels after treatment in all but one patient. Leukopenia was generally mild and not associated with infection.. Sr-89 is an effective treatment of patients with chemotherapy-refractory prostate cancer, but careful and prolonged monitoring of hematologic parameters after therapy is required.

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow Diseases; Cohort Studies; Drug Resistance, Neoplasm; Hormones; Humans; Male; Middle Aged; Pain; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Radiopharmaceuticals; Retrospective Studies; Strontium Radioisotopes; Survival Rate; Thrombocytopenia; Treatment Outcome

Strontium-89 is routinely used for pain control in advanced skeletal metastatic disease. A common side effect of Sr-89 therapy is a mild to moderate bone marrow suppression. To avoid complications from marrow suppression, a pretreatment platelet count of > 60,000/mm3 and a WBC count of > 2,400/mm3 are suggested. The authors present two patients who, despite satisfying these criteria, developed profound and prolonged bone marrow suppression after therapy. The severity of this response was most likely caused by pre-existing extensive bone marrow replacement with tumor. The contribution of local radiation therapy to bone marrow suppression is presumed to be minimal. The authors recommend that pretreatment criteria for determination of eligibility for Sr-89 therapy in selected patients be expanded to include steadily decreasing blood counts, and evaluation of extent of marrow involvement by biopsy or MR imaging.

Topics: Bone Marrow; Bone Marrow Neoplasms; Bone Neoplasms; Humans; Male; Middle Aged; Pain; Radiotherapy; Strontium Radioisotopes; Thrombocytopenia

The relative contributions of various organs to platelet production is controversial. In this study, serial histologic sections of bone marrow, spleen, liver, and lung from normal C57BL/6J mice and mice that had received three different agents which perturb normal murine thrombopoiesis (platelet antiserum, 5-fluorouracil, and radioactive strontium) were examined for the presence of megakaryocytes, utilizing morphologic and immunohistochemical techniques for their identification. In liver and lung tissue, megakaryocytes (including their naked nuclei or large cytoplasmic fragments) were rare in whole cross-sections (which included blood vessels) from normal and perturbed mice, even during periods of strong stimulation of thrombopoiesis. In contrast, megakaryocyte numbers were greatly increased in bone marrow and/or spleen tissue in these circumstances. We conclude that: 1) the bone marrow and spleen are the major thrombopoietic organs in the mouse, and 2) an insignificant fraction of thrombocytopoiesis occurs in the murine liver or lung, even during periods of greatly increased platelet production or following loss of the spleen and/or bone marrow.

Topics: Acute Disease; Animals; Blood Platelets; Bone Marrow Cells; Fluorouracil; Hematopoiesis; Lung; Megakaryocytes; Mice; Mice, Inbred C57BL; Strontium Radioisotopes; Thrombocytopenia; Tissue Distribution

A patient with metastatic prostate cancer was found to have low-grade disseminated intravascular coagulation (DIC). He had significant bone pain despite external-beam radiotherapy and was given 89Sr with subsequent thrombocytopenia and epistaxis. The patient died from generalized hemorrhage 36 days postinjection. Although it is not possible to establish a causal relationship between the 89Sr and DIC, practitioners should be alert to complications associated with the primary disorder which might occur at a time to raise concern about the intervention.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Disseminated Intravascular Coagulation; Epistaxis; Fatal Outcome; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes; Thrombocytopenia