Acute Promyelocytic Leukemia After Radium-223 Exposure for Prostate Cancer in a Chemotherapy-Naive Patient

Ra-223-dichloride is a bone-seeking targeted alpha (alpha)-emitting approved for bone metastases in prostate cancer. Here, we report a case of therapy-related acute promyelocytic leukemia (t-APL) following administration of(223)Ra, showing some evidence of a causative relationship. A patient with metastatic prostate cancer received therapy with(223)Ra, with 6 injections of the radiopharmaceutical at a standard dose of 55 kBq/kg at 4-week intervals for a cumulative administered activity of 26.3 MBq. PET/CT with(18)F-methylcholine repeated 1 month after the conclusion of(223)Ra was negative. After 8 months, he developed pancytopenia and we made a diagnosis of therapy-related acute promyelocytic leukemia (t-APL). We then studied the genomic locations of the breakpoints in the PML and RARA genes, which were at nucleotide positions 1708-09 of PML intron 3, respectively, outside the previously reported Topo II-associated hotspot region. t-APL was cured with all-trans-retinoic acid (ATRA) and arsenic trioxide. The type of PML/RARA rearrangement we identified, in absence of other myelotoxic treatments, is suggestive of a possible direct causal relationship with exposure to(223)Ra and warrants further investigations.