P1069: gonadal function and fertility preservation in pediatric patients with hodgkin lymphoma treated according to the euronet-phl-c2 protocol: the fertility add-on study

Topic: 17. Hodgkin lymphoma - Clinical Background: Five-year survival rates of childhood Hodgkin lymphoma (HL) exceed 90%. However, treatment can impair gonadal function and result fertility problems. In effort to reduce late effects, treatment protocols were adapted and gonadotoxic procarbazine was successfully omitted. The current EuroNET-PHL-C2 trial aims to reduce use of radiotherapy by intensifying chemotherapy. Effectivity of HL treatment with OEPA-COPDAC (OEPA: vincristine, etoposide, prednisolone and doxorubicin; COPDAC: cyclophosphamide, vincristine, prednisone and dacarbazine) is compared to intensified OEPA-DECOPDAC chemotherapy (COPDAC with higher cumulative dose of cyclophosphamide and additional doxorubicin and etoposide) in a randomized setting. A fertility study was incorporated in the EuroNET-PHL-C2 study to evaluate gonadotoxicity. Aims: To assess the gonadotoxic effect of the EURONET-PHL-C2 treatment regimen for Hodgkin lymphoma, by evaluating reproductive hormones, semen quality and menstrual cycle. Moreover, we evaluated the use of fertility preservation options in the studied population. Methods: Boys and girls aged <18 years, treated according to the EuroNet-PHL-C2 protocol for classical HL, were recruited across 18 sites (the Netherlands, Belgium, Germany, Austria, Czech Republic) between Jan ‘17 and Sep ‘21. All parents and patients (≥12 years old) provided written informed consent. Semen quality, serum follicle stimulating hormone (FSH) and inhibin B (boys); and serum anti-Müllerian hormone (AMH) and menstrual cycle (girls) were evaluated over time (at diagnosis, during- and directly after treatment and 2 years post-diagnosis). In addition, use of fertility preservation methods was evaluated. Results: Data of 98 boys and 100 girls were available at time of analysis, of whom 162 completed 2 years of follow-up. Median age (range) at diagnosis was 14 years (3-18) in boys and 15 years (7-18) in girls. 74 boys (76%) and 92 girls (92%) (87% postmenarchal) were postpubertal. A total of 31 patients (14 boys, 17 girls) were diagnosed at an early stage of HL (TL1), 84 boys (86%) and 83 girls (83%) in more advanced stages (49% TL2, 51% TL3, 61% COPDAC and 39% DECOPDAC). 5 girls (5%) and 6 boys (6%) received pelvic radiotherapy. At diagnosis, 48 boys (49%) delivered semen for cryopreservation and 4 (4%) underwent testicular biopsy to preserve testicular tissue. 18 (38%) semen samples were oligospermic and 4 (8%) azoospermic. Abnormal sperm count was more prevalent in boys with B symptoms (71%). To date, 29 boys delivered semen at 2 years post-diagnosis of whom 13 (45%) had abnormal sperm parameters. Of the 46 postmenarchal girls who did not receive hormonal contraceptives during treatment, 33 (72%) experienced treatment-induced amenorrhea, at least 4 (12%) had persisting amenorrhea at 2 years post-diagnosis. 4 girls (22%) who stopped taking hormonal contraceptives after treatment had no (return of) spontaneous cycle. 2 girls (2%) underwent ovariopexy. 4 girls cryopreserved oocytes before treatment and 12 cryopreserved ovarian tissue (OTC). 15 (15%) received GnRH analogues as a co-treatment. Data on FSH, inhibin B and AMH up to 2 years post-diagnosis are available by Apr 2023. Results will be compared between treatment groups, number of received chemotherapy-cycles and pubertal stage at time of diagnosis. Summary/Conclusion: 45% of boys had impaired semen quality at 2 years post HL diagnosis. Treatment-induced amenorrhea (72%) persisted in >10% of girls. Serum FSH, inhibin B and AMH are available by Apr ‘23. Results are highly valuable to determine effect of the EuroNet-PHL-C2regimen for childhood HL on fertility. Keywords: Hodgkin’s lymphoma, Cryopreservation, Fertility, Pediatric