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

Abstract

Objective: The aim of the study was to evaluate long-term ovarian function after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Subjects and methods: 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 9G4.3 years (range 1-19). At the time of the study a meanGS.D. of 13G5.5 years (range 6-27) had elapsed since the HSCT and the mean age of the participants was 22G6.3 years (range 9-41). Results: 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 23G6.3 years (range 15-41). Ten women became pregnant. Conclusions: Patients conditioned with TBI or Bu-based regimes are at high risk of ovarian failure. Intensive antileukemia therapy before HSCT including CRT especially among relapsed patients may further decrease the possibility of spontaneous menarche.

Age at Birth of First Child and Fecundity of Women Survivors of Childhood Acute Lymphoblastic Leukemia (1987−2007): A Study of the Childhood Cancer Registry of the Rhône-Alpes Region in France (ARCERRA)

“…Results were comparable in the cohorts of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and Vatanen and associates [8][9][10]. Recently, Borgmann-Staudt reported no births after TBI conditioning and only a single birth after chemotherapy conditioning among 85 women who had undergone allograft for leukemia or nonmalignant hemopathy as children and were 19 years or older at the time of follow-up [11].…”

ATG vs thiotepa with busulfan and cyclophosphamide in matched-related bone marrow transplantation for thalassemia

“…Very long-term follow-up studies have shown that BuCy may be associated with normalization of HRQoL, no second malignancies in the absence of chronic graft-versus-host disease (cGVHD), and preservation of fertility in a significant number of patients transplanted prior to age 15 years. 10 The combination of 2 myeloablative alkylating agents such as Tt and busulfan or treosulfan may result in a very high infertility rate, 20,21 which is increasingly unacceptable in the new thalassemia era of effective chelation, where a substantial proportion of individuals with ST may bear children. 22 This study compares retrospectively 2 standard preparative regimens based on BuCy in addition to either Tt or ATG for matchedrelated low-risk BMTs for ST.…”

Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study

“…Yet explicit risk or protective factors for fertility recovery could not be defined and seem to vary between individuals. Vatanen et al have shown that females undergoing HSCT and CY conditioning regimen only, were more likely to experience spontaneous puberty and menarche and required HRT less often (Vatanen et al 2014).…”

“…Recovery of fertility after HSCT therapy induced gonadal dysfunction has been reported in both sexes (Mertens et al 1998;Vatanen et al 2014;Rovo et al 2006). In males, the number of patients with spermatogenesis may rise with time (Rovo et al 2006).…”