High Endogenous DNA Damage Levels Predict Hematological Toxicity in Testicular Germ Cell Tumor Patients Treated With First-Line Chemotherapy

Abstract

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. In this study, we tested the hypothesis that patients with high endogenous DNA damage levels in PBMCs have an increased risk of developing hematological toxicity. One hundred twenty 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 cutoff level of 5.25, a value previously reported to stratify patients on the basis of their prognosis. We monitored hematological toxicity during the first cycle of chemotherapy. The mean and standard error of the mean were calculated for all variables. Patients with high DNA damage levels (>5.25) had more significant hematological toxicity with significantly lower nadir white blood cell count (P= .001), absolute neutrophil count (P= .013) and absolute lymphocyte count (ALC; P< .001). ALCs on day 0 (P= .005) and day 22 (P= .046) were also significantly lower in patients with high DNA damage levels. This study shows that higher endogenous DNA damage levels correlate with increased risk of hematological toxicity in TGCT patients. Hence, the DNA damage levels can be used to select patients for closer monitoring because of a higher risk of acute chemotherapy-related complications.