Updated Clinical Outcomes of Hematopoietic Stem Cell Transplantation Using Myeloablative Total Body Irradiation with Ovarian Shielding to Preserve Fertility
Updated Clinical Outcomes of Hematopoietic Stem Cell Transplantation Using Myeloablative Total Body Irradiation with Ovarian Shielding to Preserve Fertility
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DOI：
10.1016/j.bbmt.2019.07.039
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发表时间：
2019-12-01
影响因子：
4.3
通讯作者：
Kanda, Yoshinobu
中科院分区：
文献类型：
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作者：
Ashizawa, Masahiro;Akahoshi, Yu;Kanda, Yoshinobu
清髓性调节方案与严重的性腺毒性有关。为了保护卵巢功能，我们一直在研究清髓剂量全身照射(TBI)对卵巢的屏蔽作用。在这份报告中，我们更新了临床结果。有标准危险血液病的女性患者，年龄在40岁或以下，希望生孩子(n=19)。预适应方案为卵巢屏蔽行全身照射12Gy加环磷酰胺(120 mg/kg)或阿糖胞苷(24g/m(2))。卵巢屏蔽使卵巢的实际照射剂量从12Gy减至2-3Gy.接受造血干细胞移植(HSCT)的中位年龄为24岁(19-33岁)。移植后中位随访期为1449天(~3694天)，5年总生存率为67%，1、5年复发率分别为17%、31%。到目前为止，14名缓解中的急性髓系或淋巴细胞性白血病患者中只有2人复发。6个月和1年月经恢复率分别为42%和78%。所有月经恢复的患者均在1年内恢复月经。血清抗苗勒氏激素(AMH)水平在月经恢复后呈逐渐升高趋势。三名广泛性慢性移植物抗宿主病患者月经和血清AMH恢复延迟。3例患者5次妊娠，1例正常分娩，1例择期剖宫产，1例当前妊娠，2例自然流产。结果表明，卵巢屏蔽的清髓性TBI方案可保留HSCT后的生育力，而对标准风险患者复发率无明显增加。由于血清AMH随着时间的推移逐渐恢复，HSCT后早期AMH水平作为卵巢储备的标志物价值不大。(C)2019年美国移植和细胞治疗学会。由爱思唯尔公司出版。
Myeloablative conditioning regimens are associated with severe gonadal toxicity. To preserve ovarian function, we have been investigating ovarian shielding during total body irradiation (TBI) with a myeloablative dose. In this report, we update the clinical outcomes. Female patients with standard-risk hematologic diseases, aged 40 years or younger, who desired to have children, were included (n = 19). The conditioning regimen consisted of TBI at 12 Gy with ovarian shielding and cyclophosphamide (120 mg/kg) or cytarabine (24 g/m(2)). Ovarian shielding reduced the actual irradiation dose applied to the ovaries from 12 Gy to 2 to 3 Gy. The median age at hematopoietic stem cell transplantation (HSCT) was 24 years (range, 19 to 33 years). With a median follow-up period of 1449 days (range, 64 to 3694) after HSCT, 5-year overall survival and 1- and 5-year relapse rates were 67%, 17%, and 31%, respectively. Only 2 of 14 patients with acute myeloid or lymphoid leukemia in remission have relapsed thus far. The 6-month and 1-year cumulative rates of menstrual recovery were 42% and 78%, respectively. In all patients with menstrual recovery, menstruation recovered within 1 year. The serum anti-Mullerian hormone (AMH) level tended to gradually increase after menstrual recovery. Three patients with extensive chronic graft-versus-host disease experienced delayed recovery of menstruation and serum AMH. Five pregnancies in 3 patients resulted in normal delivery in 1, selective cesarean operation in 1, current pregnancy in 1, and natural abortion in 2. These results suggest that a myeloablative TBI regimen with ovarian shielding could preserve fertility after HSCT without an apparent increase in relapse in standard-risk patients. Because serum AMH recovered gradually over time, the AMH level during the early phase after HSCT may have little value as a marker of ovarian reserve. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.