■睾丸激素分泌受损是儿科造血干细胞移植(HSCT)后的常见后遗症,但是临床和生化结果的长期纵向趋势线仍然很少。
■单中心,回顾性分析。男性患者在1992年至2021年之间移植<18岁,在HSCT后存活≥2年,并显示,入学后,纳入与青春期发病和进展一致的临床和生化体征.每6-12个月记录一次临床和生化数据。
■在130名患者中,56%是青春期前,而44%的人在HSCT的青春期/青春期后。总的来说,44%的人表现出自发进展到青春期和正常的性腺轮廓,而其余经历过青春期逮捕(1%),FSH单独增加(19%),代偿(23%)或明显(13%)的促性腺激素性性腺功能减退症。在HSCT时仍处于青春期前的患者中,青春期后睾丸体积(TV)在统计学上较小(p0.049),而成人睾酮水平没有差异。LH和睾酮水平在20到30年间呈现镜面趋势,因为性类固醇的逐渐减少与黄体生成素的代偿性增加有关。据报道,85%的患者有不同程度的性腺功能障碍,51%,32%和0%的患者接受全身照射(TBI),busulfan-,基于环磷酰胺和曲硫丹的方案,分别。TBI和白消安队列与无性腺事件病程的最低概率相关(p<0.0001),而在使用曲硫丹后,它实现了100%的目标。在白消安之后检测到的性腺毒性在统计学上大于曲硫丹(p0.024)。仅化疗方案与统计学上较大的TV相关(p<0.001),与TBI相比,睾酮水平较高(p0.008)和促性腺激素水平较低(p<0.001)。因此,与白消安相比,后者的性腺衰竭风险增加2倍(OR2.34,CI1.08-8.40),而青春期前HSCT与风险降低相关(OR0.15,CI0.08-0.30).
■a)青春期前接受HSCT的患者睾丸内分泌功能障碍的风险降低,尽管成人电视较小;b)患者在青春期完全达到后,睾酮水平呈下降趋势,尽管LH有代偿性增加;c)与白消安相比,曲硫丹与性腺功能减退症的发生率在统计学上较低相关,随着电视大型化的趋势,较高的睾酮水平和较低的促性腺激素。
Impaired testosterone secretion is a frequent sequela following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.
Monocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 years after HSCT and showing, upon enrollment, clinical and biochemical signs consistent with pubertal onset and progression were included. Clinical and biochemical data collected every 6-12 months were recorded.
Of 130 patients enrolled, 56% were prepubertal, while 44% were peri-/postpubertal upon HSCT. Overall, 44% showed spontaneous progression into puberty and normal gonadal profile, while the remaining experienced pubertal arrest (1%), isolated increase of FSH (19%), compensated (23%) or overt (13%) hypergonadotropic hypogonadism. Post-pubertal testicular volume (TV) was statistically smaller among patients still pre-pubertal upon HSCT (p 0.049), whereas no differences were recorded in adult testosterone levels. LH and testosterone levels showed a specular trend between 20 and 30 years, as a progressive decrease in sexual steroids was associated with a compensatory increase of the luteinizing hormone. A variable degree of gonadal dysfunction was reported in 85%, 51%, 32% and 0% of patients following total body irradiation- (TBI), busulfan-, cyclophosphamide- and
treosulfan-based regimens, respectively. TBI and busulfan cohorts were associated with the lowest probability of gonadal event-free course (p<0.0001), while it achieved 100% following
treosulfan. A statistically greater gonadotoxicity was detected after busulfan than
treosulfan (p 0.024). Chemo-only regimens were associated with statistically larger TV (p <0.001), higher testosterone (p 0.008) and lower gonadotropin levels (p <0.001) than TBI. Accordingly, the latter was associated with a 2-fold increase in the risk of gonadal failure compared to busulfan (OR 2.34, CI 1.08-8.40), whereas being pre-pubertal upon HSCT was associated with a reduced risk (OR 0.15, CI 0.08-0.30).
a) patients pre-pubertal upon HSCT showed a reduced risk of testicular endocrine dysfunction, despite smaller adult TV; b) patients showed downwards trend in testosterone levels after full pubertal attainment, despite a compensatory increase in LH; c)
treosulfan was associated to a statistically lower occurrence of hypogonadism than busulfan, with a trend towards larger TV, higher testosterone levels and lower gonadotropins.