Long-term outcomes of dasatinib-induced pulmonary arterial hypertension: a population-based study

被引:92
|
作者
Weatherald, Jason [1 ,2 ,3 ,4 ]
Chaumais, Marie-Camille [3 ,5 ,6 ]
Savale, Laurent [1 ,2 ,3 ]
Jais, Xavier [1 ,2 ,3 ]
Seferian, Andrei [1 ,2 ,3 ]
Canuet, Matthieu [7 ]
Bouvaist, Helene [8 ]
Magro, Pascal [9 ]
Bergeron, Anne [10 ,11 ]
Guignabert, Christophe [1 ,3 ]
Sitbon, Olivier [1 ,2 ,3 ]
Simonneau, Gerald [1 ,2 ,3 ]
Humbert, Marc [1 ,2 ,3 ]
Montani, David [1 ,2 ,3 ]
机构
[1] Univ Paris Saclay, Univ Paris Sud, Fac Med, Le Kremlin Bicetre, France
[2] Hop Bicetre, AP HP, Serv Pneumol, Le Kremlin Bicetre, France
[3] Hop Marie Lannelongue, INSERM UMR S 999, Le Plessis Robinson, France
[4] Univ Calgary, Dept Med, Div Respirol, Calgary, AB, Canada
[5] Univ Paris Saclay, Univ Paris Sud, Fac Pharm, Chatenay Malabry, France
[6] Hop Antoine Beclere, Serv Pharm, DHU TORINO, Clamart, France
[7] Hop Univ Strasbourg, Nouvel Hop Civil, Serv Pneumol, Strasbourg, France
[8] CHU Genoble Alpes, Serv Cardiol, Grenoble, France
[9] CHRU Tours, Serv Pneumol, Tours, France
[10] Hop St Louis, AP HP, Serv Pneumol, Paris, France
[11] Univ Paris Diderot, UMR CRESS 1153, Sorbonne Paris Cite, Biostat & Clin Epidemiol Res Team, Paris, France
关键词
CHRONIC MYELOID-LEUKEMIA; ABL INHIBITORS IMATINIB; TYROSINE KINASE; CHRONIC-PHASE; PLEURAL EFFUSION; NILOTINIB; THERAPY; DETERIORATION; RESISTANT; DIAGNOSIS;
D O I
10.1183/13993003.00217-2017
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
This study aimed to describe the long-term outcomes of pulmonary arterial hypertension (PAH) induced by dasatinib. 21 incident, right heart catheterisation-confirmed cases of dasatinib-induced PAH were identified from the French Pulmonary Hypertension Registry. Clinical and haemodynamic variables were compared from baseline to last follow-up (median (range) 24 (1-81) months). Median age was 52 years and 15 patients were female (71%). 19 patients received dasatinib for chronic myelogenous leukaemia for a median (range) duration of 42 (8-74) months before PAH diagnosis. No bone morphogenic protein receptor-2 (BMPR2) mutations were found in the 10 patients tested. Dasatinib was uniformly discontinued and 11 patients received PAH medications. Four patients died during follow-up. New York Heart Association functional class improved from 76% in class III/IV to 90% in class I/II (p<0.01). Median (range) 6-min walk distance improved from 306 (0-660) to 430 (165-635) m (p<0.01). Median (range) mean pulmonary arterial pressure improved from 45 (30-70) to 26 (17-50) mmHg (p<0.01) and pulmonary vascular resistance from 6.1 (3.2-27.3) to 2.6 (1.2-5.9) Wood units (p<0.01). Patients treated with PAH medications had worse baseline haemodynamics but similar long-term outcomes to untreated patients. PAH persisted in 37% of patients. Dasatinib-induced PAH frequently improves after discontinuation but persisted in over one-third of patients, therefore systematic follow-up is essential.
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页数:11
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