Clinical presentation, diagnosis and management of therapy-related hematological disorders in women with epithelial ovarian cancer treated with chemotherapy and poly-ADP-ribose polymerase inhibitors: A single-center experience

Int J Cancer. 2021 Jan 1;148(1):170-177. doi: 10.1002/ijc.33269. Epub 2020 Sep 16.

Abstract

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.

Keywords: PARP-inhibitors; clinical management; epithelial ovarian cancer; hematological monitoring; therapy-related hematological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Blood Cell Count
  • Bone Marrow / pathology
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / mortality
  • Female
  • Hematologic Diseases / chemically induced
  • Hematologic Diseases / diagnosis*
  • Hematologic Diseases / epidemiology
  • Hematologic Diseases / therapy
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Incidence
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects*
  • Retrospective Studies
  • Transplantation, Homologous

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors