Abstract 14355: Early Screening of Dasatinib-Induced Pulmonary Arterial Hypertension Using Computed Tomography Imaging, the Prognostic Significance of Pulmonary Arterial Diameter/Ascending Aortic Diameter Ratio and Spleen Size.

Introduction: Dasatinib, a BCR-ABL tyrosine kinase inhibitor (BA-TKI) is a potent agent for the treatment of chronic myelogenous leukemia (CML). However, it induces rare complication of pulmonary arterial hypertension (PAH), whereas Imatinib has a protective effect on PAH. A pathologic mechanism underlying Dasatinib-induced PAH (DiPAH) has been studied in rodents. Its toxic effects on pulmonary vasculature exhibit only in PAH models, not in control, suggesting a two-hit theory. The incidence and the cause of DiPAH in human are poorly understood, thereby this study aimed to identify the prevalence and the susceptibility of DiPAH in clinical settings and to find marker-based screening strategies for DiPAH. Methods: We retrospectively investigated 61 consecutive patients who received Dasatinib in our hospital. We determined the onset of DiPAH with (1) New electrocardiographic changes indicating right ventricular hypertrophy (2) Systolic pulmonary artery pressure (PAP) measured by echocardiography >40 mmHg (3) Pulmonary arterial diameter (PD)/Ascending aortic diameter (AD) ratio measured by computed tomography in axial image >1 or >1.1 fold increase in PD/AD ratio if baseline PD/AD ratio is >1 (4) Mean PAP measured by right heart catheterization >25 mmHg. Results: Thirteen patients developed DiPAH 657±150 days from the initiation of Dasatinib treatment. Baseline patients characteristics and echocardiographic parameters did not differ between DiPAH group (PH) and non-DiPAH group (NPH). Baseline PD/AD ratio was higher in PH (NPH 0.83±0.02 vs. PH 0.98±0.04, P=0.0038). The prominent increase in PD/AD ratio was observed in PH (pre 0.98±0.04 vs. post 1.11±0.03, P=0.009), but the slight increase was also found in NPH (pre 0.83±0.02 vs. post 0.85±0.02, P=0.04). Delta PD/AD ratio was higher in PH (P=0.0015). Interestingly, EUTOS score, a prognostic indicator of CML, was lower in PH (NPH 55.8±4.7 vs. PH 33.6±9.9, P=0.037). Spleen size (SS) below the costal margin was significantly larger in NPH (NPH 13.1±3.2 cm vs. PH 0±0 cm, P<0.001). On ROC analysis to predict DiPAH, inclusive model using PD/AD ratio, PD, EUTOS score and SS rendered highest power with an AUC of 0.93 (P=0.04). Conclusions: Higher PD/AD ratio at the baseline significantly correlated with the development of DiPAH, supporting the possibility of two-hit theory for the underlying mechanism of DiPAH. Spleen might play protective roles in the development of DiPAH. [ABSTRACT FROM AUTHOR]