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Radium-223 dichloride is an α-emitting radiopharmaceutical that localizes to bone matrix and is approved for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. The cumulative impact of Ra-223 and other therapeutic agents for metastatic CRPC on myelosuppression in bone marrow is unknown. The phase 3 randomized, double-blind, placebo-controlled ALSYMPCA trial of Ra-223 in patients with CRPC and symptomatic bone metastases demonstrated a significant improvement in overall survival. Of the 571 patients subsequently followed for 3 years, few in either the Ra-223 or placebo arm experienced hematologic adverse events. Little evidence shows secondary malignancies associated with Ra-223 treatment; only 2 cases of secondary leukemia after Ra-223 treatment were found in the literature. The goals of this review were to summarize safety and efficacy results from clinical trials and institutional safety data pertaining to hematologic adverse events occurring with Ra-223, and to discuss practical management issues.Radium-223 is a radiopharmaceutical localizing to bone and is approved for treatment of bone metastases in prostate cancer. Safety and efficacy data regarding hematologic events from radium-223 therapy are discussed.