Objective

Female patients treated with alkylating agents in childhood are at risk for ovarian impairment. We aimed at describing the pattern of residual ovarian function in a cohort of survivors of hematological malignancies and/or hematopoietic stem cell transplantation (HSCT) and assessing the relationship between cyclophosphamide equivalent dose (CED) and anti-Müllerian hormone (AMH).

Design and methods

Gonadal health was clinically and biochemically assessed in 124 post-menarchal survivors who underwent treatment for pediatric hematological malignancies and/or HSCT between 1992 and 2019.

Results

Overt 'premature ovarian insufficiency' (POI) was detected in 72.1 and 3.7% of transplanted and non-transplanted patients, respectively; milder 'diminished ovarian reserve' (DOR) in 16.3 and 22.2%. In non-transplanted patients, increasing CED values were associated with lower AMH-SDS (P = 0.04), with the threshold of 7200 g/m² being the best discriminator between DOR/POI and normal ovarian function (AUC: 0.75 on ROC analysis) and with an observed decrease of 0.14 AMH-SDS for each CED increase of 1 g/m². In addition, age at diagnosis ≥10 years played a detrimental role on ovarian reserve (P = 0.003). In the HSCT group, irradiation was associated with a statistically significant reduction in AMH-SDS (P = 0.04).

Conclusions

In non-transplanted patients, CED ≥ 7200 mg/m² was associated with a DOR, while younger age at diagnosis played a protective role on ovarian reserve. As a result of the data collected, we propose a systematic algorithm to assess iatrogenic gonadal impairment in young female patients exposed to chemo-radiotherapy in childhood for hematological disorders.

中文翻译：

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血清抗苗勒管激素作为儿童癌症治疗和/或造血干细胞移植后卵巢储备的标志物：性腺评估系统方法的建议

客观的

在儿童期接受烷化剂治疗的女性患者有卵巢损伤的风险。我们旨在描述血液系统恶性肿瘤和/或造血干细胞移植 (HSCT) 幸存者队列中残余卵巢功能的模式，并评估环磷酰胺等效剂量 (CED) 和抗苗勒管激素 (AMH) 之间的关系。

设计和方法

对 1992 年至 2019 年间接受小儿血液系统恶性肿瘤和/或 HSCT 治疗的 124 名月经后幸存者的性腺健康进行了临床和生化评估。

结果

在移植和非移植患者中分别检测到 72.1% 和 3.7% 的明显“卵巢早衰”（POI）；较温和的“卵巢储备减少”（DOR）分别为 16.3% 和 22.2%。在非移植患者中，增加的 CED 值与较低的 AMH-SDS 相关（P  = 0.04），阈值 7200 g/m ²是 DOR/POI 与正常卵巢功能之间的最佳区分（ROC 分析中的 AUC：0.75） ) 并且观察到 CED 每增加 1 g/m ²就会减少 0.14 AMH-SDS 。此外，诊断年龄≥10 岁对卵巢储备有不利影响（P  = 0.003）。在 HSCT 组中，照射与 AMH-SDS 的统计学显着降低相关（P = 0.04)。

结论

在非移植患者中，CED ≥ 7200 mg/m ²与 DOR 相关，而诊断时年龄较小则对卵巢储备有保护作用。作为收集到的数据的结果，我们提出了一种系统的算法来评估在儿童时期因血液疾病而接受化学放射治疗的年轻女性患者的医源性性腺损伤。