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Annals of Hematology

, Volume 97, Issue 1, pp 95–100 | Cite as

Pleural effusion and molecular response in dasatinib-treated chronic myeloid leukemia patients in a real-life Italian multicenter series

  • Alessandra IurloEmail author
  • Sara Galimberti
  • Elisabetta Abruzzese
  • Mario Annunziata
  • Massimiliano Bonifacio
  • Roberto Latagliata
  • Patrizia Pregno
  • Dario Ferrero
  • Federica Sorà
  • Ester Maria Orlandi
  • Carmen Fava
  • Daniele Cattaneo
  • Cristina Bucelli
  • Gianni Binotto
  • Ester Pungolino
  • Mario Tiribelli
  • Antonella Gozzini
  • Gabriele Gugliotta
  • Fausto Castagnetti
  • Fabio Stagno
  • Giovanna Rege-Cambrin
  • Bruno Martino
  • Luigiana Luciano
  • Massimo Breccia
  • Simona Sica
  • Monica Bocchia
  • Fabrizio Pane
  • Giuseppe Saglio
  • Gianantonio Rosti
  • Giorgina Specchia
  • Agostino Cortelezzi
  • Michele Baccarani
Original Article

Abstract

Pleural effusion (PE) represents the leading cause of dasatinib (DAS) discontinuation. However, the pathogenic mechanism of this adverse event (AE) is unknown and its management unclear. We investigated if a DAS dose reduction after the first PE would prevent the recurrence of this AE. We retrospectively collected data on all the cases of PE in CML-chronic phase (CP) DAS-treated patients from November 2005 to February 2017 in 21 Italian hematological centers. We identified 196 cases of PE in a series of 853 CML-CP DAS-treated patients (incidence 23.0%). DAS starting dose was 100 mg/day in 70.4% of patients, less than 100 mg/day in 14.3%, and more than 100 mg/day in the remaining cases. Median time from DAS start to PE was 16.6 months. At first PE development, 28.6% of patients were in MMR, and 37.8% in deep molecular response (DMR). DAS was temporary interrupted in 71.9% of cases, with a dose reduction in 59.2%. Recurrence was observed in 59.4% of the cases. Treatment was definitively discontinued due to PE in 29.1% of the cases. Interestingly, among patients whose DAS dosage was reduced, 59.5% experienced PE recurrence. DAS dose reduction after the first episode of PE did not prevent recurrence of this AE. Therefore, once a MMR or a DMR is achieved, different strategies of DAS dose management can be proposed prior to the development of PE, such as daily dose reduction or, as an alternative option, an on/off treatment with a weekend drug holiday.

Keywords

Chronic myeloid leukemia Dasatinib Pleural effusion Molecular response Dose reduction 

Notes

Compliance with ethical standards

Conflict of interest

A. Iurlo: consultant for and honoraria from Novartis, Bristol-Myers Squibb, Incyte, and Pfizer; E. Abruzzese: consultant for Novartis and Bristol-Myers Squibb; R. Latagliata: honoraria from Novartis, Bristol-Myers Squibb, Celgene; D. Ferrero: financial support from Novartis and Bristol-Myers Squibb; C. Fava: honoraria from Novartis and Bristol-Myers Squibb; M. Tiribelli: consultant for and honoraria from Novartis, Bristol-Myers Squibb, and Incyte; A. Gozzini: honoraria from Novartis and Bristol-Myers Squibb; G. Gugliotta: consultant for and honoraria from Novartis and Bristol-Myers Squibb; F. Castagnetti: consultant for and honoraria from Novartis, Bristol-Myers Squibb, Pfizer, and Incyte; G. Rege-Cambrin: honoraria from Novartis and Bristol-Myers Squibb; M. Breccia: consultant for Bristol-Myers Squibb, Novartis, Pfizer, and Incyte; F. Pane: research support from Novartis, consultant for Novartis, Bristol-Myers Squibb, and Incyte, honoraria from Novartis and Bristol-Myers Squibb; G. Saglio: consultant for and honoraria from Bristol-Myers Squibb, Novartis, Incyte, and Celgene; G. Rosti: consultant for and honoraria from Novartis, Bristol-Myers Squibb, Incyte, Pfizer, and Roche; M. Baccarani: consultant for and honoraria from Novartis, Bristol-Myers Squibb, Pfizer, and Incyte; the remaining authors had no relevant conflicts of interest to disclose.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Alessandra Iurlo
    • 1
    Email author
  • Sara Galimberti
    • 2
  • Elisabetta Abruzzese
    • 3
  • Mario Annunziata
    • 4
  • Massimiliano Bonifacio
    • 5
  • Roberto Latagliata
    • 6
  • Patrizia Pregno
    • 7
  • Dario Ferrero
    • 8
  • Federica Sorà
    • 9
  • Ester Maria Orlandi
    • 10
  • Carmen Fava
    • 11
  • Daniele Cattaneo
    • 1
  • Cristina Bucelli
    • 1
  • Gianni Binotto
    • 12
  • Ester Pungolino
    • 13
  • Mario Tiribelli
    • 14
  • Antonella Gozzini
    • 15
  • Gabriele Gugliotta
    • 16
  • Fausto Castagnetti
    • 16
  • Fabio Stagno
    • 17
  • Giovanna Rege-Cambrin
    • 18
  • Bruno Martino
    • 19
  • Luigiana Luciano
    • 20
  • Massimo Breccia
    • 6
  • Simona Sica
    • 9
  • Monica Bocchia
    • 21
  • Fabrizio Pane
    • 20
  • Giuseppe Saglio
    • 11
  • Gianantonio Rosti
    • 16
  • Giorgina Specchia
    • 22
  • Agostino Cortelezzi
    • 1
  • Michele Baccarani
    • 16
  1. 1.Hematology Division, IRCCS Ca’ Granda - Maggiore Policlinico Hospital FoundationUniversity of MilanMilanItaly
  2. 2.Department of Clinical and Experimental Medicine, Section of HematologyUniversity of PisaPisaItaly
  3. 3.Hematology Unit, Sant’Eugenio HospitalTor Vergata UniversityRomeItaly
  4. 4.Hematology UnitCardarelli HospitalNaplesItaly
  5. 5.Department of Medicine, Section of HematologyUniversity of VeronaVeronaItaly
  6. 6.Department of Cellular Biotechnologies and HematologyUniversity “La Sapienza” of RomeRomeItaly
  7. 7.Hematology UnitAzienda Ospedaliero Universitaria Città della Salute e della ScienzaTurinItaly
  8. 8.Hematology UnitUniversity of TurinTurinItaly
  9. 9.Institute of HematologyUniversità Cattolica del Sacro CuoreRomeItaly
  10. 10.Hematology UnitFondazione IRCCS Policlinico San MatteoPaviaItaly
  11. 11.Hematology Division, Ospedale MaurizianoUniversity of TurinTurinItaly
  12. 12.Hematology UnitUniversity of PadovaPaduaItaly
  13. 13.Division of HematologyASST Grande Ospedale Metropolitano NiguardaMilanItaly
  14. 14.Division of Hematology and BMTAzienda Sanitaria Universitaria Integrata di UdineUdineItaly
  15. 15.Haematology, AOU CareggiUniversity of FirenzeFlorenceItaly
  16. 16.Institute of Hematology “L. and A. Seràgnoli,” Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University HospitalUniversity of BolognaBolognaItaly
  17. 17.Hematology UnitFerrarotto HospitalCataniaItaly
  18. 18.Division of Hematology and Internal Medicine, “San Luigi Gonzaga” University Hospital, OrbassanoUniversity of TurinTurinItaly
  19. 19.Hematology UnitGrande Ospedale Metropolitano “Bianchi Melacrino Morelli”Reggio CalabriaItaly
  20. 20.Hematology Unit“Federico II” University of NaplesNaplesItaly
  21. 21.Hematology UnitAzienda Ospedaliera Universitaria Senese and University of SienaSienaItaly
  22. 22.Hematology and Transplants UnitUniversity of BariBariItaly

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