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

被引:10
作者
Todisco, Elisabetta [1 ]
Gigli, Federica [1 ]
Mantiero, Mara [2 ]
Sammassimo, Simona [1 ]
Pastano, Rocco [1 ]
Ronchini, Chiara [3 ]
Parma, Gabriella [4 ]
Lapresa, Maria Teresa [4 ]
Iori, Anna Paola [5 ]
Bertolini, Francesco [6 ]
Corsini, Chiara [6 ]
Gregato, Giuliana [6 ]
Poletti, Claudia [6 ]
Colombo, Nicoletta [7 ,8 ]
Tarella, Corrado [1 ,9 ]
机构
[1] European Inst Oncol IRCCS, Oncohematol Div, IEO, Milan, Italy
[2] Fdn IRCCS Natl Canc Inst, Gynecol Oncol Unit, Milan, Italy
[3] European Inst Oncol IRCCS, Lab Clin Genom, IEO, Milan, Italy
[4] European Inst Oncol IRCCS, Dept Gynecol, IEO, Milan, Italy
[5] Sapienza Univ, Dept Cellular Biotechnol & Hematol, Rome, Italy
[6] European Inst Oncol IRCCS, Lab Hematol Oncol, IEO, Milan, Italy
[7] European Inst Oncol, Gynecol Canc Program, Milan, Italy
[8] Univ Milano Bicocca, Milan, Italy
[9] Univ Milan, Dept Hlth Sci, Milan, Italy
关键词
clinical management; epithelial ovarian cancer; hematological monitoring; PARP-inhibitors; therapy-related hematological disorders; MAINTENANCE THERAPY; MYELOID NEOPLASMS; DOUBLE-BLIND; MUTATION;
D O I
10.1002/ijc.33269
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:170 / 177
页数:8
相关论文
共 22 条
[1]   Up-Regulation of Two Distinct p53-DNA Binding Functions by Covalent Poly(ADP-ribosyl)ation: Transactivating and Single Strand Break Sensing [J].
Alvarez-Gonzalez, Rafael ;
Mendoza-Alvarez, Hilda ;
Frey, Manfred ;
Zentgraf, Hanswalter .
CANCER INVESTIGATION, 2013, 31 (09) :563-570
[2]   The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia [J].
Arber, Daniel A. ;
Orazi, Attilio ;
Hasserjian, Robert ;
Thiele, Jurgen ;
Borowitz, Michael J. ;
Le Beau, Michelle M. ;
Bloomfield, Clara D. ;
Cazzola, Mario ;
Vardiman, James W. .
BLOOD, 2016, 127 (20) :2391-2405
[3]   Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial [J].
Coleman, Robert L. ;
Oza, Amit M. ;
Lorusso, Domenico ;
Aghajanian, Carol ;
Oaknin, Ana ;
Dean, Andrew ;
Colombo, Nicoletta ;
Weberpals, Johanne, I ;
Clamp, Andrew ;
Scambia, Giovanni ;
Leary, Alexandra ;
Holloway, Robert W. ;
Amenedo Gancedo, Margarita ;
Fong, Peter C. ;
Goh, Jeffrey C. ;
O'Malley, David M. ;
Armstrong, Deborah K. ;
Garcia-Donas, Jesus ;
Swisher, Elizabeth M. ;
Floquet, Anne ;
Konecny, Gottfried E. ;
McNeish, lain A. ;
Scott, Clare L. ;
Cameron, Terri ;
Maloney, Lara ;
Isaacson, Jeff ;
Goble, Sandra ;
Grace, Caroline ;
Harding, Thomas C. ;
Raponi, Mitch ;
Sun, James ;
Lin, Kevin K. ;
Giordano, Heidi ;
Ledermann, Jonathan A. .
LANCET, 2017, 390 (10106) :1949-1961
[4]   A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - An NRG Oncology/Gynecologic Oncology Group study [J].
Coleman, Robert L. ;
Sill, Michael W. ;
Bell-McGuinn, Katherine ;
Aghajanian, Carol ;
Gray, Heidi J. ;
Tewari, Krishnansu S. ;
Rubin, Steven C. ;
Rutherford, Thomas J. ;
Chan, John K. ;
Chen, Alice ;
Swisher, Elizabeth M. .
GYNECOLOGIC ONCOLOGY, 2015, 137 (03) :386-391
[5]   ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease [J].
Colombo, N. ;
Sessa, C. ;
du Bois, A. ;
Ledermann, J. ;
McCluggage, W. G. ;
McNeish, I. ;
Morice, P. ;
Pignata, S. ;
Ray-Coquard, I. ;
Vergote, I. ;
Baert, T. ;
Belaroussi, I. ;
Dashora, A. ;
Olbrecht, S. ;
Planchamp, F. ;
Querleu, D. ;
Banerjee, S. ;
Blecharz, P. ;
Bruchim, I. ;
Cibula, D. ;
Concin, N. ;
Davidson, B. ;
Devouassoux-Shisheboran, M. ;
Ferrero, A. ;
Glasspool, R. ;
Gonzalez-Martin, A. ;
Heinzelmann-Schwarz, V. ;
Joly, F. ;
Kim, J. W. ;
Kridelka, F. ;
Lorusso, D. ;
Mahner, S. ;
Mikami, M. ;
Mirza, M. R. ;
Nicum, S. ;
O'Donnell, D. M. ;
Pautier, P. ;
Rodolakis, A. ;
Sehouli, J. ;
Selcukbiricik, F. ;
Singh, N. ;
Tan, D. S. P. ;
Timmerman, D. ;
Tognon, G. ;
van der Velden, J. ;
Witteveen, P. O. ;
Zeimet, A. G. .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2019, 29 (04) :728-760
[6]   Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers [J].
de Bono, Johann ;
Ramanathan, Ramesh K. ;
Mina, Lida ;
Chugh, Rashmi ;
Glaspy, John ;
Rafii, Saeed ;
Kaye, Stan ;
Sachdev, Jasgit ;
Heymach, John ;
Smith, David C. ;
Henshaw, Joshua W. ;
Herriott, Ashleigh ;
Patterson, Miranda ;
Curtin, Nicola J. ;
Byers, Lauren Averett ;
Wainberg, Zev A. .
CANCER DISCOVERY, 2017, 7 (06) :620-629
[7]   Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].
Doehner, Hartmut ;
Estey, Elihu ;
Grimwade, David ;
Amadori, Sergio ;
Appelbaum, Frederick R. ;
Buechner, Thomas ;
Dombret, Herve ;
Ebert, Benjamin L. ;
Fenaux, Pierre ;
Larson, Richard A. ;
Levine, Ross L. ;
Lo-Coco, Francesco ;
Naoe, Tomoki ;
Niederwieser, Dietger ;
Ossenkoppele, Gert J. ;
Sanz, Miguel ;
Sierra, Jorge ;
Tallman, Martin S. ;
Tien, Hwei-Fang ;
Wei, Andrew H. ;
Lowenberg, Bob ;
Bloomfield, Clara D. .
BLOOD, 2017, 129 (04) :424-447
[8]   Role of Surgical Outcome as Prognostic Factor in Advanced Epithelial Ovarian Cancer: A Combined Exploratory Analysis of 3 Prospectively Randomized Phase 3 Multicenter Trials By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO) [J].
du Bois, Andreas ;
Reuss, Alexander ;
Pujade-Lauraine, Eric ;
Harter, Philipp ;
Ray-Coquard, Isabelle ;
Pfisterer, Jacobus .
CANCER, 2009, 115 (06) :1234-1244
[9]   Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J].
Farmer, H ;
McCabe, N ;
Lord, CJ ;
Tutt, ANJ ;
Johnson, DA ;
Richardson, TB ;
Santarosa, M ;
Dillon, KJ ;
Hickson, I ;
Knights, C ;
Martin, NMB ;
Jackson, SP ;
Smith, GCM ;
Ashworth, A .
NATURE, 2005, 434 (7035) :917-921
[10]   Revised International Prognostic Scoring System for Myelodysplastic Syndromes [J].
Greenberg, Peter L. ;
Tuechler, Heinz ;
Schanz, Julie ;
Sanz, Guillermo ;
Garcia-Manero, Guillermo ;
Sole, Francesc ;
Bennett, John M. ;
Bowen, David ;
Fenaux, Pierre ;
Dreyfus, Francois ;
Kantarjian, Hagop ;
Kuendgen, Andrea ;
Levis, Alessandro ;
Malcovati, Luca ;
Cazzola, Mario ;
Cermak, Jaroslav ;
Fonatsch, Christa ;
Le Beau, Michelle M. ;
Slovak, Marilyn L. ;
Krieger, Otto ;
Luebbert, Michael ;
Maciejewski, Jaroslaw ;
Magalhaes, Silvia M. M. ;
Miyazaki, Yasushi ;
Pfeilstoecker, Michael ;
Sekeres, Mikkael ;
Sperr, Wolfgang R. ;
Stauder, Reinhard ;
Tauro, Sudhir ;
Valent, Peter ;
Vallespi, Teresa ;
van de Loosdrecht, Arjan A. ;
Germing, Ulrich ;
Haase, Detlef .
BLOOD, 2012, 120 (12) :2454-2465