Onco-Hematology Division, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan, Italy.
Int J Cancer. 2021 Jan 1;148(1):170-177. doi: 10.1002/ijc.33269. Epub 2020 Sep 16.
We investigated the occurrence and management of therapy-related hematological disorders (tr-HDs) in women with epithelial ovarian cancer (EOC) exposed to poly-ADP-ribose polymerase inhibitors (PARPi), after previous chemotherapy. We analyzed 130 consecutive EOC patients treated with PARPi at the European Institute of Oncology, Milan. In line with the literature, overall survival of the entire population was 37% at 5.5 years (89% were advanced stages). Cell blood counts were collected prior to start PARPi, at each new cycle and at monthly intervals. Patients displaying persistent and/or marked hematological abnormalities underwent bone marrow evaluation, with cytogenetic and molecular analysis. Nine patients (6,9%) developed tr-HDs, after a median 22.8 months of PARPi exposure. Two patients died early and could not be treated. Two patients have no indication for active treatment and are presently under close hematological monitoring. Five patients underwent chemotherapy followed, in three cases, by allogeneic hematopoietic transplantation: three patients are in complete remission of their hematological and gynecological malignancies at 13, 19, and 25 months; the remaining two patients died due to progression of their hematological disease. We show the potential risk of hematological disorders in EOC patients treated with chemotherapy and prolonged PARPi therapy. In our series, tr-HDs incidence was higher compared to recent reports in large series. Our observations suggest careful monitoring in order to conclusively define, on large series and prolonged follow-up, the actual risk of tr-HDs in patients under PARPi. Notably, prompt diagnosis of hematological abnormalities and appropriate management allow achievement of remission from severe hematological complications, at least in most patients.
我们研究了既往接受过化疗的上皮性卵巢癌（EOC）女性患者在接受多聚 ADP-核糖聚合酶抑制剂（PARPi）治疗后发生的治疗相关血液学疾病（tr-HD）及其处理方法。我们分析了在米兰欧洲肿瘤研究所接受 PARPi 治疗的 130 例连续的 EOC 患者。与文献一致，所有患者的 5.5 年总生存率为 37%（89%为晚期）。在开始使用 PARPi 之前、每个新周期以及每月采集细胞血液计数。对于持续存在和/或明显血液学异常的患者，进行骨髓评估，并进行细胞遗传学和分子分析。在 PARPi 暴露中位数为 22.8 个月后，9 例（6.9%）患者发生 tr-HD。2 例患者早期死亡，无法进行治疗。2 例患者无活性治疗指征，目前正在密切进行血液学监测。5 例患者随后接受了化疗，其中 3 例在化疗后进行了异基因造血移植：3 例患者的血液学和妇科恶性肿瘤完全缓解，缓解时间分别为 13、19 和 25 个月；其余 2 例患者因血液系统疾病进展而死亡。我们表明，在接受化疗和延长 PARPi 治疗的 EOC 患者中存在血液系统疾病的潜在风险。与最近在大型系列中报告的结果相比，我们的系列中 tr-HD 的发生率更高。我们的观察结果表明，需要进行仔细监测，以便在大系列和长期随访中确定 PARPi 治疗患者发生 tr-HD 的实际风险。值得注意的是，及时诊断血液学异常并进行适当处理，至少可以使大多数患者避免严重血液学并发症。
