Hematological toxic side effects associated with epithelial ovarian cancer chemotherapy and PARPi therapy: clinical manifestations, diagnosis and management

Endothytretic ovarian cancer (EOC) is the fifth most common cancer among women and the most fatal of gynaecological malignancies, usually in its late stages.
platinum chemotherapy after surgery is still the standard treatment of gold.
However, most patients will relapse, and in recent years poly-ADP-UC polymerase inhibitors (PARPi) have been developed as new and effective anti-cancer therapies, especially for carriers of mutations in the breast cancer gene (BRCA1/ BRCA2).
clinical trials have shown that PARPi's efficacy in EOC has significantly improved progression-free survival in relapse.
shown survival benefits in patients with BRCA mutations (SOLO2 trial) and BRCA wild patients (OV16/NOVA, ARIEL3 trial).
, SOLO1 trials have shown that Olapali maintenance therapy reduces the risk of disease progression or death by 70 percent in patients newly diagnosed with EOC with BRCA mutations.
these studies ushered in a new era of EOC management by approving parpi maintenance therapy, and there are currently several clinical trials evaluating the efficacy of multiple PARPis.
PARPi performs its anti-cancer activity through so-called "synthetic lethality" mechanisms, and normal cells proficient in iso-recombinant repair (HRR) can survive parp suppression.
, normal cells, especially rapidly dividing cells, such as hematocytes, may also be affected by DNA repair.
there have been reports of frequent adverse events of blood toxicity after PARPi treatment.
a recent meta-analysis by
showed a decrease in grade 3 or 4 neutral granulocytes in patients receiving PARPi, with the rates of plate reduction and anemia of 32.9 per cent, 15.9 per cent and 9.1 per cent, respectively.
these side effects usually occur within the first few months of treatment and are controlled by temporary treatment interruptions or dose reductions.
but less is understood about late hematological toxicity.
if hematological toxicity is not eliminated after the interruption of the drug, regular blood test monitoring and other tests are recommended.
to assess the long-term hematological complications of PARPi, a retrospective analysis was conducted on 130 patients treated with PARPi at the European Oncology Institute (IEO) in Milan.
and describes the early diagnosis and management of blood system diseases (tr-HDs) associated with treatment.
this paper analyzes 130 EOC patients who received PARPi treatment at the European Oncology Institute (IEO) in Milan between 2010 and 2018.
start PARPi, extraterrocytic blood is collected for cellular blood counting (CBC) at each new cycle and monthly interval.
bone marrow (BM) assessment, including morphological, immunosymodymic, cytogenetics and FISH analysis, was performed in patients exhibiting persistent and/or significant hematological abnormalities, using Ion Reporter software for analysis.
use descriptive statistics to report data related to patient demographics, clinical pathological characteristics, and treatment.
study showed that all patients who developed tr-HDs received first-line chemotherapy in platinum and yew alkanes and platinum-based chemotherapy before PARPi.
9 patients (6.9%) developed tr-HD after a median PARPi treatment of 22.8 months.
, tr-HDs occurred in 7 patients in the Olapali group, tr-HDs in 2 patients in the Lucapali group, and tr-HDs in the Nirapali group.
9 patients were diagnosed with uncertainty cloning cell reduction (CCUS), 5 with MDS (4 with MDS with too many parent cells (EB): 3 EB2 and 1 EB1; 1 case of MDS Cannot be classified), 2 other patients were diagnosed with acute granulocytic leukemia (AML) (1 case of AML-FAB M6 and 1 case of AML associated with bone marrow growth abnormalities (MRC), and 1 patient was diagnosed with acute lymphoblastic leukemia (ALL), FAB L3.
after tr-HD diagnosis, all patients except CCUS patients stopped PARPi.
2 MDS-EB2 patients died prematurely and could not be treated.
two patients (CCUS and MDS-U) were not actively treated and are currently undergoing rigorous hematological monitoring.
Five other patients received chemotherapy, three of whom received allogeneic hemagnetic transplants: three were in complete remission of blood diseases and gynaecological malignancies at 13, 19 and 25 months, and the remaining two patients died as a result of the progression of blood diseases.
Table1 130 EOC chemotherapy patients with clinical characteristics during treatment with PARPi and PARPi Table2 treatment-related blood patients characteristics and treatment of Table 3 hematopoietic stem cell transplant patients characteristics of the study showed that EOC patients receiving chemotherapy and subsequent long-term PARPi treatment have a potential risk of late blood toxicity, compared with other studies, the incidence of tr-HDs in this study is higher.
recommend careful hematological monitoring to final determine the actual risk of tr-HD in PARPi patients in large samples and long-term follow-up.
manage patient tr-HD under PARPi, timely diagnosis and proper treatment can alleviate serious hematological complications.
references: Todisco, E; Gigli, F; Mantiero, M; Tarella, C; et al,Clinical presentation, diagnosis andmanagement of Therapy-Related Hematological Disorders in Women with EpithelialOvarian Cancer treated with Chemotherapy and Poly-ADP-Ribose PolymeraseInhibitors (PARP-i): a single Center experience. Int J Cancer. 2021 Jan 01; 148 (1): 170-177. Zhang Lili Zhang Shi former Source: Zhang Shi's former public number Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Metz Medical, and are not authorized to reproduce, and any media, website or individual shall indicate "Source: Mes Medicine" when authorizing their reprint.
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