G542(P) Comparing fertility outcomes in paediatric patients treated with busulfan or treosulfan prior to haematopoietic stem cell transplant

Abstract

Background Haematopoietic stem cell transplant (HCT) can be used to treat malignant and non-malignant conditions. Prior to HCT, patients have conditioning with chemotherapy to ablate their bone marrow to make space for transplanted cells. Previous studies suggest that busulfan results in long-term gonadal toxicity. No previous studies have compared gonadal toxicity outcomes after treatment with busulfan with treosulfan, a newer agent with similar marrow toxicity to busulfan but with reduced non-marrow toxcitiy. Our aim was to determine whether there are differences in pubertal and fertility outcomes in patients treated with treosulfan compared with busulfan. Methods Inclusion criteria were patients who had received either busulfan or treosulfan or treosulfan with thiotepa, only one HCT and were aged 14 years and above in August 2018. Eligible patients were reviewed in clinic as part of their routine follow-up, thus research ethical approval was not required. FSH, LH, oestradiol, and pubertal history were noted. Ovarian reserve was estimated in female patients by measuring serum AMH. Male patients had serum testosterone measured and were also offered semen analysis. Results Thirty-five patients fitted the inclusion criteria, of which twenty-five wanted to be reviewed (71%); seventeen females and eight males. Mean age at HCT was 13 years, mean age at review was 19 years and mean years since HCT was 5 years. Female patients treated with busulfan or treosulfan with thiotepa (n=14) had minimal AMH and none of these patients were having regular periods. Females treated with treosulfan (n=3) had normal AMH and regular periods without needing hormone replacement. Only four male patients opted for a semen analysis and all had significantly reduced sperm counts. Discussion Our results suggest that females treated with treosulfan have minimal (if any) reduction in ovarian reserve compared to other conditioning regimens which casue significant compromise. Although this was a small study, and thus not suitable for statistical analysis, the clinical findings are marked. Future studies should further investigate optimal doses of treosulfan that could be used to achieve bone marrow engraftment and limit long-term effects on fertility.