Testicular and sperm DNA damage after treatment with fludarabine for chronic lymphocytic leukaemia

This study investigated whether chemotherapy using fludarabine (FLU) caused testicular damage and if cytotoxicity could be detected as sperm DNA damag e in the single cell Comet assay, A patient with chronic lymphocytic leukae mia requesting preservation of fertility was treated with seven monthly cyc les of fludarabine (45.8 mg total dose per cycle). Testicular assessments, serum follicle stimulating hormone (FSH), luteinizing hormone (LS-I), and t estosterone measurements, semen analysis and sperm Comet assays were carrie d out at presentation (pre-FLU therapy), after 1 and 7 months of FLU treatm ent, and finally at 11 months after completion of chemotherapy. We found th at testicular damage occurred within a month, as indicated by reduced testi cular volume, oligozoospermia, elevated FSH and LB, and lower testosterone concentrations. Spermatozoa with a large range of DNA damage were detected in the samples from both the control and treated men. DNA damage in the spe rmatozoa was marked by 7 months of FLU treatment. The high levels of sperm DNA damage seen during and possibly persisting after treatment suggests tha t caution should be exercised if the ejaculates from these men are used for in-vitro fertility treatment. Further experiments are needed to assess the biological significance of these DNA changes; it may, however, be prudent at present to be cautious when counselling these patients.