Pubertal outcomes of children transplanted with allogeneic stem cells after myeloablative total body irradiation or busulfan: Influence of age and sex is confirmed, while a role of chronic graft-versus-host disease in delayed puberty onset is revealed.

Abstract

Myeloablative conditioning before allogeneic HSCT during childhood exposes to serious long-term complications, especially gonadal dysfunction. Pubertal issues are less described than other post-HSCT sequelae in childhood. Pubertal development and biological gonadal parameters were assessed in a retrospective monocentric cohort of prepubertal patients who underwent HSCT after myeloablative conditioning with TBI or busulfan between 1981 and 2017. Seventy-four patients (28 girls and 46 boys) were included. No spontaneous pubertal development was found in 50% of girls and 10% of boys (P<.001), and delayed puberty or no spontaneous pubertal development was found in 57% of girls and 24% of boys (P=.009). HRT was used in 82% of girls and 24% of boys (P<.001). In univariate analysis, TBI conditioning (P=.05), female sex (P<.001), acute GVHD (P=.05), extensive chronic GVHD (P=.021), steroid treatment >6months (P=.016), and malignant diseases (P=.016) were associated with no spontaneous pubertal development, whereas TBI conditioning (P=.003) and extensive chronic GVHD (P=.005) were associated with delayed puberty. In multivariate analysis, factors independently associated with no spontaneous puberty onset were female sex (P=.001) and age >10years (P=.033). Factors independently associated with delayed puberty were extensive chronic GVHD (P=.041) and age >10years (P=.031). This study highlighted the toxicity of MAC in prepubescent children: TBI did worse, but this was especially true for the most susceptible patients (girls, leukemic patients, and patients older than 10years). It suggests a possible role of GVHD in delayed puberty.