Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence

Abstract

The aim of the study was to evaluate long-term ovarian function after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Predictive factors for ovarian function were evaluated among 92 adult or pubertal female survivors transplanted at Huddinge and Helsinki University Hospital during 1978-2000, at a mean age of 9±4.3 years (range 1-19). At the time of the study a mean±s.d. of 13±5.5 years (range 6-27) had elapsed since the HSCT and the mean age of the participants was 22±6.3 years (range 9-41). Spontaneous puberty based on breast development occurred in 40 and menarche in 30 of the 70 girls who were prepubertal at transplantation. Six out of 20 girls who received HSCT after initiation of pubertal development recovered their ovarian function. Younger age at HSCT, conditioning without total body irradiation (TBI), and a non-leukemia diagnosis predicted the spontaneous menarche. The incidence of menarche was higher after fractioned vs single fraction TBI (P<0.05), cyclophosphamide (Cy) vs busulfan (Bu)-based conditioning (P<0.05), and among leukemia patients transplanted at first remission vs later remissions (P<0.01) and with no cranial irradiation (cranial radiotherapy, CRT) vs given CRT (14-24 Gy) (P<0.01). The majority of recipients conditioned with only Cy vs TBI (P<0.001) or vs Bu-based regimens (P<0.01) showed preserved ovarian function and required no estrogen replacement at their latest follow-up visit at a mean age of 23±6.3 years (range 15-41). Ten women became pregnant. Patients conditioned with TBI or Bu-based regimes are at high risk of ovarian failure. Intensive anti-leukemia therapy before HSCT including CRT especially among relapsed patients may further decrease the possibility of spontaneous menarche.