ABSTRACT
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.
Subject(s)
Antineoplastic Agents/adverse effects , Hypertension, Pulmonary/chemically induced , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Thiazoles/adverse effects , Adolescent , Adult , Adverse Drug Reaction Reporting Systems , Aged , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Benzamides , Bone Morphogenetic Protein Receptors, Type II/genetics , Calcium Channel Blockers/therapeutic use , Dasatinib , Drug Utilization/statistics & numerical data , Endothelin Receptor Antagonists , Female , Follow-Up Studies , Hemodynamics/drug effects , Humans , Hydroxyurea/therapeutic use , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/epidemiology , Imatinib Mesylate , Male , Middle Aged , Piperazines/adverse effects , Piperazines/therapeutic use , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Registries , Thiazoles/pharmacology , Thiazoles/therapeutic use , Treatment OutcomeSubject(s)
Amyloidosis/etiology , Amyloidosis/pathology , Skin Diseases/etiology , Skin Diseases/pathology , HumansABSTRACT
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