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Ann Hematol. 2018 Jan;97(1):95-100. doi: 10.1007/s00277-017-3144-1. Epub 2017 Oct 2.

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

Author information

1
Hematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, University of Milan, Milan, Italy. aiurlo@policlinico.mi.it.
2
Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.
3
Hematology Unit, Sant'Eugenio Hospital, Tor Vergata University, Rome, Italy.
4
Hematology Unit, Cardarelli Hospital, Naples, Italy.
5
Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
6
Department of Cellular Biotechnologies and Hematology, University "La Sapienza" of Rome, Rome, Italy.
7
Hematology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
8
Hematology Unit, University of Turin, Turin, Italy.
9
Institute of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy.
10
Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
11
Hematology Division, Ospedale Mauriziano, University of Turin, Turin, Italy.
12
Hematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, University of Milan, Milan, Italy.
13
Hematology Unit, University of Padova, Padua, Italy.
14
Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
15
Division of Hematology and BMT, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.
16
Haematology, AOU Careggi, University of Firenze, Florence, Italy.
17
Institute of Hematology "L. and A. Seràgnoli," Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Bologna, Italy.
18
Hematology Unit, Ferrarotto Hospital, Catania, Italy.
19
Division of Hematology and Internal Medicine, "San Luigi Gonzaga" University Hospital, Orbassano, University of Turin, Turin, Italy.
20
Hematology Unit, Grande Ospedale Metropolitano "Bianchi Melacrino Morelli", Reggio Calabria, Italy.
21
Hematology Unit, "Federico II" University of Naples, Naples, Italy.
22
Hematology Unit, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena, Italy.
23
Hematology and Transplants Unit, University of Bari, Bari, Italy.

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; Dose reduction; Molecular response; Pleural effusion

PMID:
28971265
DOI:
10.1007/s00277-017-3144-1
[Indexed for MEDLINE]

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