Preservation of fertility in women undergoing reduced-intensity conditioning allogeneic transplantation with a fludarabine-based regime.
Preservation of fertility in women undergoing reduced-intensity conditioning allogeneic transplantation with a fludarabine-based regime.
复制标题
使用基于氟达拉滨的方案进行低强度条件同种异体移植的女性的生育能力的保留。
DOI：
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发表时间：
2012
期刊：
影响因子：
6.2
通讯作者：
Panagiotis D. Kottaridis
中科院分区：
文献类型：
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作者：
S. Papageorgiou;O. Ahmed;N. Narvekar;M. Davies;Panagiotis D. Kottaridis
不孕症是血液病恶性和非恶性疾病患者接受常规或大剂量化疗或造血干细胞移植（SCT）的主要晚期效应(1)。大多数已发表的关于接受造血干细胞移植的患者的数据都来自于研究，这些研究报告了主要清除骨髓方案的受者的条件调节的有害影响（2,3）。低强度调节SCT （RIC-SCT）最大限度地减少了全身照射作为移植前调节方案的一部分，因此降低了短期和长期的毒性。我们之前报道过基于氟达拉滨、美法兰和campaign - 1h联合使用RIC方案的移植物抗宿主病的低非复发死亡率和低发病率(4)。本研究旨在证明RIC对卵巢功能的影响。从我们的临床数据库中确定2001年至2009年接受RIC移植的育龄女性患者。我们回顾性地收集了在晚期效应诊所随访的女性患者的数据，并确定了那些(1)保持月经；（ii）黄体生成素（LH）、卵泡刺激素（FSH）和雌二醇水平正常；（iii）卵泡的放射学证据；(4)继续怀孕。通过测定基础血清FSH、LH、雌二醇和窦卵泡计数来评估卵巢功能。如果FSH和LH值小于10 IU/L，且窦卵泡计数大于8，则认为卵巢活性和生育潜力最佳。30例19 ~ 44岁的女性患者接受了RIC移植。其中，26例患者在移植前的化疗中已经出现了性腺损伤（FSH、LH升高和闭经），因此被排除在进一步的研究之外。30例患者中有2例在移植前保留了生育能力（FSH、LH和周期正常），甚至在移植后也保留了卵巢功能。此外，另外两名在移植前接受大量预处理的患者在移植后11个月和37个月怀孕，尽管移植后的激素水平与绝经期一致（表1）。患者年龄分别为19岁、25岁、33岁和35岁（表1）。诊断为霍奇金淋巴瘤2例，骨髓增生异常综合征2例。患者接受同胞异体移植（n=1）或匹配的非相关供体移植（n=3）， RIC由氟达拉滨/美法兰/ campaign - 1h （n=3）和氟达拉滨/曲硫芬/ campaign - 1h （n=1）组成。在这四名患者中，有两名尽管记录了高促性腺激素，但还是怀孕了。其余2例患者移植后均有月经，卵巢功能相对保留，LH、FSH、雌二醇均可证明。超声成像
Infertility is a major late effect in patients receiving either conventional or high-dose chemotherapy or hematopoietic stem-cell transplantation (SCT) for hematological malignancies and nonmalignant disorders (1). Most of the published data in relation to patients undergoing a hematopoietic SCT come from studies reporting the deleterious effect of the conditioning in recipients of primarily myeloablative regimens (2, 3). Reduced-intensity conditioning SCT (RIC-SCT) has minimized the use of total-body irradiation as part of the pretransplantation conditioning regime and has therefore reduced the short-term and long-term toxicity. We have previously reported low rate of nonrelapse mortality and low incidence of graftversus-host disease with a RIC protocol based on a fludarabine, melphalan, and campath-1H combination (4). The present study aimed to document the effect of RIC on ovarian function. Female patients of reproductive age who underwent an RIC transplantation from 2001 to 2009 were identified from our clinical database. We retrospectively collected data on female patients who were being followed up in the late effects clinic and identified those who had (i) maintained menstruation; (ii) normal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels; (iii) radiologic evidence of ovarian follicles; and (iv) went on to conceive. Ovarian function was assessed by measuring basal serum FSH, LH, estradiol, and antral follicle count. Ovarian activity and fertility potential was considered optimal if FSH and LH values were less than 10 IU/L and antral follicle count were greater than 8. Thirty female patients aged 19 to 44 years who underwent an RIC transplantation were identified. Of these, 26 had already sustained gonadal damage (as it was demonstrated by increased FSH, LH, and amenorrhea) from antecedent chemotherapy before the transplantation and were excluded from further study. Two of 30 patients had preserved fertility (normal FSH, LH, and cycling) before the transplantation and retained ovarian function even after the transplantation. In addition, two more patients who were heavily pretreated before the transplantation became pregnant at 11 and 37 months after transplantation despite the fact that the hormonal profile after transplantation was consistent with menopause (Table 1). The ages of the patients were 19, 25, 33, and 35 years (Table 1). Diagnoses were Hodgkin lymphoma in two patients and myelodysplastic syndromes in two patients. The patients received either a sibling allograft (n=1) or matched unrelated-donor transplant (n=3) with RIC that consisted of fludarabine/ melphalan/campath-1H (n=3) and fludarabine/tresulfan/campath-1H (n=1). Of these four patients, two went on to become pregnant despite documented high gonadotrophins. The remaining two patients both had menstruation after transplantation and relative preservation of ovarian function as evidenced by LH, FSH, and estradiol. Ultrasound imaging