Guo Meihua, Lv Jian, Chen Xiaotong, Wu Mengliang, Zhao Qilei, Hai Xin
Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Oncol. 2022 May 12;12:887026. doi: 10.3389/fonc.2022.887026. eCollection 2022.
Acute promyelocytic leukemia (APL) is extremely fatal if treatment is delayed. Management of APL in pregnancy is a challenging situation. Arsenic trioxide (ATO) is successfully applied to treat APL. ATO can be transformed into different arsenic species [arsenite (As), monomethylated arsenic (MMA, consists of MMA and MMA), dimethylated arsenic (DMA, consists of DMA and DMA), and arsenate (As)], which produce different toxic effects. Investigating the maternal and fetal exposure to arsenic species is critical in terms of assessing maternal and fetal outcomes, choice of optimal treatment, and making decisions for attempting to preserve the obstetrical and fetal wellbeing. In this study, maternal blood and amniotic fluid (AF) from APL patients treated with ATO in pregnancy and blood samples of non-pregnant patients were collected. Concentrations of inorganic arsenic (iAs, iAs = As+As), MMA, and DMA were analyzed by high-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS). The difference in arsenic species of plasma between pregnant patients and non-pregnant patients, distribution of arsenic compounds in AF and maternal plasma, and arsenic penetration into AF were explored. The outcomes of pregnant women treated with ATO and their fetus were analyzed. No significant differences in arsenic concentration, percentage, and methylation index [PMI: primary methylation index (MMA/iAs); SMI: secondary methylation index (DMA/MMA)] between pregnant women and non-pregnant women ( > 0.05) were observed. The mean ratios of AF to maternal plasma were as follows: iAs, 2.09; DMA, 1.04; MMA, 0.49; and tAs, 0.98. Abortion rate is higher with the diagnosis at an earlier gestational age, with 0%, 67%, and 100% of pregnancies ending in abortion during the third, second, and first trimester, respectively. The age of the pregnant women, the dose of ATO, and the duration of fetal exposure had no influence on fetal outcomes. All APL women achieved complete remission (CR). Collectively, ATO and its metabolites can easily cross the placenta. Levels and distribution of arsenic species in maternal plasma and AF gave evidence that arsenic species had a different ability to penetrate the placenta into AF (iAs > DMA > MMA) and indicated a relatively high fetal exposure to ATO and its metabolites . Gestational age at diagnosis was more likely to be closely related to fetal outcomes, but had no effects on mother outcomes.
急性早幼粒细胞白血病（APL）若治疗延迟则极其致命。孕期APL的管理是一个具有挑战性的情况。三氧化二砷（ATO）已成功应用于治疗APL。ATO可转化为不同的砷物种[亚砷酸盐（As）、一甲基砷（MMA，由MMA和MMA组成）、二甲基砷（DMA，由DMA和DMA组成）以及砷酸盐（As）]，它们会产生不同的毒性作用。就评估母婴结局、选择最佳治疗方案以及做出旨在维护母婴健康的决策而言，调查母婴对砷物种的暴露情况至关重要。在本研究中，收集了孕期接受ATO治疗的APL患者的母血和羊水（AF）以及非孕期患者的血样。采用高效液相色谱 - 氢化物发生 - 原子荧光光谱法（HPLC - HG - AFS）分析无机砷（iAs，iAs = As + As）、MMA和DMA的浓度。探讨了孕期患者与非孕期患者血浆中砷物种的差异、AF和母血中砷化合物的分布以及砷向AF的渗透情况。分析了接受ATO治疗的孕妇及其胎儿的结局。未观察到孕妇与非孕妇之间砷浓度、百分比及甲基化指数[PMI：一级甲基化指数（MMA/iAs）；SMI：二级甲基化指数（DMA/MMA）]有显著差异（>0.05）。AF与母血的平均比值如下：iAs为2.09；DMA为1.04；MMA为0.49；总砷（tAs）为0.98。诊断时孕周越小流产率越高，在孕晚期、孕中期和孕早期妊娠终止于流产的比例分别为0%、67%和100%。孕妇年龄、ATO剂量及胎儿暴露持续时间对胎儿结局无影响。所有APL女性均实现完全缓解（CR）。总体而言，ATO及其代谢产物可轻易穿过胎盘。母血和AF中砷物种的水平及分布表明，砷物种穿透胎盘进入AF的能力不同（iAs > DMA > MMA），且表明胎儿对ATO及其代谢产物的暴露相对较高。诊断时的孕周更可能与胎儿结局密切相关，但对母亲结局无影响。
