High endogenous DNA damage levels predict haematological toxicity in testicular germ cell tumor patients treated with first-line chemotherapy

Abstract Background Testicular germ cell tumors (TGCTs) are an excellent example of chemosensitive disease. However, cisplatin-based chemotherapy has significant side effects, including myelosuppression. Previously, we found endogenous DNA damage level in peripheral blood mononuclear cells (PBMCs) to be an independent prognostic marker. Herein, we have tested the hypothesis that patients with high endogenous DNA damage levels in PBMCs have an increased risk of developing haematological toxicity. Methods 120 chemotherapy-naive TGCT patients treated in the National Cancer Institute and the St. Elisabeth Cancer Institute in Bratislava, Slovakia, from 2012 to 2018 were enrolled. All patients received platinum-based chemotherapy with granulocyte-colony stimulating factor support. On the day of starting treatment, we measured the DNA damage levels in PBMCs using the Comet assay. We used the cut-off level of 5.25, a value previously found to stratify patients based on their prognosis. We monitored haematological toxicity during the 1st cycle of chemotherapy. The mean and SEM were calculated for all variables. Results Patients with high DNA damage levels (>5.25) had more significant haematological toxicity with significantly lower nadir white blood cell count ( p =0.001), absolute neutrophil count ( p =0.013) and absolute lymphocyte count (ALC, p p =0.005) and day 22 ( p =0.046) were also significantly lower in patients with high DNA damage levels. Conclusions This study shows that higher endogenous DNA damage levels correlate with increased risk of haematological toxicity in TGCT patients. Hence, the DNA damage levels can be used to select patients for closer monitoring due to higher risk of acute chemotherapy-related complications.