Exacerbated Renal and Hematologic Toxicities to Ifosfamide and Doxorubicin-Based Chemotherapy in a Patient with Retroperitoneal Liposarcoma Harboring a Germline Mutation in the WRN Gene

Abstract

Werner's syndrome is caused by the inactivation of both WRN alleles and is characterized by premature aging and increased risk of neoplasms, especially those of mesenchymal origins, such as sarcomas. Given the characteristic genomic instability, patients with this syndrome are more susceptible to develop toxicities when exposed to cytotoxic agents, such as alkylators and anthracyclines. The impact of the monoallelic WRN mutation on treatment-associated toxicities is poorly understood. Here, we report a patient with locally advanced dedifferentiated liposarcoma of the retroperitoneum harboring a heterozygous germline inactivation mutation in the WRN gene, who was treated with a classic regimen of ifosfamide and doxorubicin and developed exacerbated and prolonged hematological and renal toxicities.

Keywords: Hematological and renal toxicities; Liposarcoma; WRN; Werner's syndrome.