在接受聚（ADP-核糖）聚合酶（PARP）抑制剂（PARPis）治疗的晚期高级别卵巢癌（aHGOC）患者中，种系 BRCA 致病性变异（gBRCA-PV）的存在可能会增加骨髓突变的风险导致细胞毒治疗后骨髓增生异常肿瘤（MDS-pCT）或急性髓系白血病（AML-pCT），因为它也由造血祖细胞以杂合性表达。我们的目的是根据 gBRCA-PV 状态调查 PARPi 后 MDS/AML-pCT 的发生情况。我们进行了一项回顾性单中心研究，以评估 aHGOC 和已知 gBRCA-PV 状态接受治疗的患者的 MDS/AML-pCT。从 2017 年 2 月到 2022 年 12 月，在任何治疗方案中，维持 PARPi 至少 8 周。终点是在 PARPi 治疗期间和治疗后经历过 MDSs-pCT 和 AMLs-pCT 的患者在 gBRCA-PV 携带者和非携带者中的比例总共包括 166 名患者：95 名 (57%) 患有 gBRCA-PV，72% 因复发性疾病接受 PARPi。 gBRCA-PV 携带者和非携带者之间的 PARPi 前后化疗线数、中位总生存期和中位随访时间相当。中位随访时间为 40.0（95% 置信区间：35.7-44.3）个月后，10 名患者（6%）被诊断为 MDS-pCT，4 名患者（2%）被诊断为 AML-pCT。在 gBRCA-PV 携带者中观察到较高比例的 MDSs/AMLs-pCT（10% 对比 2%；P = 0.16），特别是 MDSs-pCT（9% 对比 1%；P = 0.04）。对于接受 PARPi 的 aHGOC 患者，gBRCA-PV 的发生与 PARPi 治疗后较高的 MDS-pCT 风险以及可能的骨髓肿瘤风险相关，尤其是在疾病复发的情况下。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Among patients with advanced high-grade ovarian carcinoma (aHGOC) treated with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), the presence of a germline BRCA pathogenic variant (gBRCA-PV) may increase the risk of bone marrow mutagenesis resulting in postcytotoxic therapy myelodysplastic neoplasms (MDS-pCT) or acute myeloid leukemia (AML-pCT), as it is expressed in heterozygosity also by hematopoietic progenitors. We aimed to investigate the occurrence of post-PARPi MDSs/AMLs-pCTs according to gBRCA-PV status.We conducted a retrospective single-center study to evaluate MDS/AML-pCT in patients with aHGOC and a known gBRCA-PV status receiving at least 8 weeks of maintenance PARPi, in any line of therapy, from February 2017 to December 2022. The endpoint was the proportion of patients who experienced MDSs-pCT and AMLs-pCT during and after treatment with PARPi, in gBRCA-PV carriers and non-carriers.A total of 166 patients were included: 95 (57%) had a gBRCA-PV and 72% received PARPi for recurrent disease. The number of lines of chemotherapies before and after PARPi, median overall survival, and median follow-up were comparable between gBRCA-PV carriers and non-carriers. After a median follow-up of 40.0 (95% confidence interval: 35.7-44.3) months, 10 (6%) patients were diagnosed with an MDS-pCT and 4 (2%) with an AML-pCT. A higher proportion of MDSs/AMLs-pCT (10% versus 2%; P = 0.16) and, in particular, of MDSs-pCT (9% versus 1%; P = 0.04) was observed among gBRCA-PV carriers.The presence of a gBRCA-PV is associated with a higher risk of MDS-pCT and possibly of myeloid neoplasms after PARPi in patients with aHGOC who received PARPi, especially in the setting of recurrent disease.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.