Long telomeres at baseline and male sex are main determinants of telomere loss following chemotherapy exposure in lymphoma patients

Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first-line CHT. TL was measured by southern blot at each CHT cycle and after 1 year from CHT completion. Median age was 59 yrs (range 22-77). Median number of CHT cycles was 6 (range 3-6). The majority of patients (79%, n = 27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1 year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p < 0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre-treatment evaluation. Stratifying the analysis by gender and age only young women (<51 years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.