PMID: identifiant
de la référence Pubmed : |
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 (22451584) |
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| titre : |
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Pulmonary arterial hypertension in patients treated by dasatinib. |
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| auteur(s) : |
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David Montani1, Emmanuel Bergot2, Sven Günther1, Laurent Savale1, 3, Anne Bergeron4, Arnaud Bourdin5, Helene Bouvaist6, Matthieu Canuet7, Christophe Pison8, Margareth Macro9, Patrice Poubeau10, Barbara Girerd1, 3, Delphine Natali1, 3, Christophe Guignabert1, 3, Frédéric Perros1, 3, Dermot S O'Callaghan1, 3, Xavier Jaïs1, 3, Pascale Tubert-Bitter11, Gérard Zalcman2, Olivier Sitbon1, 3, Gérald Simonneau1, 3, Marc Humbert ( ) 1, 3 |
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| laboratoire : |
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| résumé : |
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BACKGROUND: The French pulmonary hypertension (PH) registry allows the survey of epidemiological trends. Isolated cases of precapillary PH have been reported in patients who have chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. METHODS AND RESULTS: This study was designed to describe incident cases of dasatinib-associated PH reported in the French PH registry. From the approval of dasatinib (November 2006) to September 30, 2010, 9 incident cases treated by dasatinib at the time of PH diagnosis were identified. At diagnosis, patients had moderate to severe precapillary PH with functional and hemodynamic impairment. No other incident PH cases were exposed to other tyrosine kinase inhibitors at the time of PH diagnosis. Clinical, functional, or hemodynamic improvements were observed within 4 months of dasatinib discontinuation in all but 1 patient. Three patients required PH treatment with endothelin receptor antagonist (n=2) or calcium channel blocker (n=1). After a median follow-up of 9 months (min-max 3-36), the majority of patients did not demonstrate complete clinical and hemodynamic recovery, and no patients reached a normal value of mean pulmonary artery pressure (≤20 mm Hg). Two patients (22%) died at follow-up (1 of unexplained sudden death and 1 of cardiac failure in the context of septicemia, respectively, 8 and 12 months after dasatinib withdrawal). The lowest estimate of incident PH occurring in patients exposed to dasatinib in France was 0.45%. CONCLUSIONS: Dasatinib may induce severe precapillary PH fulfilling the criteria of pulmonary arterial hypertension, thus suggesting a direct and specific effect of dasatinib on pulmonary vessels. Improvement is usually observed after withdrawal of dasatinib. |
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| domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0009-7322 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1161/CIRCULATIONAHA.111.079921 |
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| journal : |
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| Circulation (Circulation) |
| Publisher |
American Heart Association |
| ISSN |
0009-7322 (eISSN : 1524-4539) |
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| Audience : |
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internationale |
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| date de publication : |
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01/05/2012 |
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date de publication
électronique : |
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26/03/2012 |
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| volume : |
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125 |
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| numéro : |
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17 |
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| page, identifiant, ... : |
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2128-37 |
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| mots-clés auteur : |
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adverse drug events – pulmonary hypertension – vascular complications – chronic myeloid leukemia dasatinib |
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