急性白血病患者卵巢冷冻保存和移植的安全性: 一个病例系列研究。
Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: A case series.
发表日期:2023 Sep 02
作者:
Murat Sönmezer, Yavuz Emre Şükür, Koray Görkem Saçinti, Sinan Özkavukçu, Duygu Kankaya, Cem Somer Atabekoğlu, Güldane Cengiz Seval, Kutluk H Oktay
来源:
Am J Obstet Gynecol
摘要:
随着成功率的提高,卵巢组织冷冻保存近年来已成为生育保护的标准技术。然而,通过卵巢组织移植引入恶性细胞仍是急性白血病患者的主要关注。为了调查在急性白血病幸存者中进行自体卵巢组织移植的安全性,对4名患有急性髓系白血病和2名患有急性淋巴细胞性白血病的女性进行了临床、组织病理学和分子学数据分析。在通过缓慢冻结法冷冻保存卵巢皮层的66-100%后,所有女性均接受了高剂量免疫抑制化疗作为异基因造血干细胞移植的预处理方案。在卵巢组织移植前:1)评估了卵泡数量、血清AMH和FSH水平以确诊原发性卵巢功能不全;2)所有受者均通过了造血专科医生的审核;3)适当时对代表性皮层条进行组织学(H&E)、免疫组织化学(CD3、CD20、CD34、CD68、CD117、CD163、PAX-5、Tdt、溶菌酶、MPO)和分子标记(BCR/ABL p190和AML1/ETO)检测筛查白血病浸润。卵巢组织冷冻保存时的中位年龄为20岁(15-32岁)。在进行造血干细胞移植之前,所有患者均接受了包括ARA-C+Daunorubicin或BFM-95在内的诱导/巩固化疗并处于缓解状态。平均血清AMH在卵巢组织冷冻保存前为1.9±1.7ng/ml。在所有病例中,卵巢组织筛查没有发现白血病细胞。根据卵巢组织冷冻保存后的中位时间(41-120个月),经腹腔镜手术或带或不带机器人辅助进行了卵巢移植。在平均3个月(2.5-4个月)后,所有患者的卵巢功能恢复了,其中每个女性有2个活产。卵巢组织移植后的中位移植存活时间为35.5个月(18-57个月)。在中位随访期为51个月(20-74个月)之后,所有患者仍然没有复发。有一个病例,在剖腹产时移植物被切除,并且免疫组化白血病标记为阴性。我们的长期随访结果显示,在接受异基因造血干细胞移植前,白血病患者进行卵巢组织移植后没有复发的证据。这一安全性可解释为这些患者在进行卵巢组织冷冻保存之前,通过非性腺毒性的诱导化疗被诱导进入缓解状态。我们建议,在接受异基因造血干细胞移植前,不应将卵巢组织冷冻保存排除作为患有白血病的年轻女性的生育保护选择。版权所有©2023。Elsevier Inc.出版。
With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias.To investigate the safety of performing autologous ovarian tissue transplantation in acute leukemia survivors.Clinical, histopathological and molecular data of four women with acute myeloid leukemia and two with acute lymphoblastic leukemia, who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66-100% of an ovarian cortex with a slow freezing method, all women received high dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Prior to the ovarian tissue transplantation: 1) Antral follicle counts, serum AMH and FSH levels were assessed to confirm primary ovarian insufficiency; 2) all recipients were cleared by their hematologist-oncologists; 3) representative cortical strips were screened for leukemia infiltration by histologic (H&E), immunohistochemical (CD3, CD 20, CD34, CD 68, CD 117, CD 163, PAX-5, Tdt, lysozyme, MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate.The median age was 20 years (15-32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction/consolidation chemotherapy that included ARA-C+ Daunorubicin" or "BFM-95" and were in remission. Mean serum AMH was 1.9±1.7ng/ml before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (range; 41-120 months) following ovarian tissue cryopreservation. Ovarian function resumed in all patients after a mean of 3 months (range 2.5-4 months), and two women of each had one live birth. The median graft longevity was 35.5 months post-ovarian tissue transplantation (18-57 months). After a median follow-up of 51 months (20-74 months), all patients remained relapse-free. In one patient, the graft was removed during cesarean section and was negative for immunochemical leukemia markers.Our long-term follow-up demonstrated no evidence of disease relapse after ovarian tissue transplantation in patients with acute leukemia who received allogenic hematopoietic stem cell transplantation. This safety profile may be explained by the fact that these patients are induced into remission by non-gonadotoxic induction chemotherapy before undergoing ovarian tissue cryopreservation. We propose that ovarian tissue cryopreservation should not be excluded as a fertility preservation option for young women with leukemia who are due to receive preconditioning chemotherapy prior to allogeneic hematopoietic stem cell transplantation.Copyright © 2023. Published by Elsevier Inc.