Toya Takumi, Nagatomo Yuji, Kagami Kazuki, Yukino Midori, Yasuda Risako, Namba Takayuki, Ido Yasuo, Kobayashi Shinichi, Masaki Nobuyuki, Yada Hirotaka, Kimura Fumihiko, Adachi Takeshi
Division of Cardiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan.
Division of Hematology, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan.
Int J Cardiovasc Imaging. 2019 Aug;35(8):1435-1442. doi: 10.1007/s10554-019-01548-2. Epub 2019 Feb 4.
Periodic echo-based screening to detect early stages of a rare complication of dasatinib, pulmonary arterial hypertension (PAH), is inefficient and weakens the potential benefit of dasatinib as a potent drug for chronic myelogenous leukemia (CML). This study aimed to identify the predisposing factors of DASA-PAH to stratify high-risk patients for dasatinib-induced PAH (DASA-PAH).
Sixty consecutive adult patients who received dasatinib were enrolled in this case-control study. We defined DASA-PAH when at least one of the following four criteria was met: (1) recent electrocardiographic changes indicating right ventricular pressure overload, (2) estimated systolic pulmonary arterial pressure > 40 mmHg measured by Doppler echocardiography; (3) computed tomography (CT)-measured pulmonary artery to aorta diameter (PaD/AoD) ratio > 1; and (4) mean pulmonary arterial pressure > 25 mmHg and pulmonary artery wedge pressure < 15 mmHg measured by right heart catheterization.
We identified 13 patients with DASA-PAH among 59 patients analyzed. Baseline PaD/AoD ratios of patients who developed DASA-PAH (PH group) were significantly larger than those who did not (NPH group). A dramatic rise in PaD/AoD ratio after dasatinib treatment was observed. Interestingly, the EUTOS score and spleen size were significantly smaller in the PH than in the NPH group.
High baseline PaD/AoD ratio and low EUTOS score were associated with DASA-PAH development. The spleen might play a protective role against DASA-PAH.
基于周期性回声的筛查用于检测达沙替尼罕见并发症——肺动脉高压(PAH)的早期阶段,效率低下,且削弱了达沙替尼作为慢性粒细胞白血病(CML)有效药物的潜在益处。本研究旨在确定达沙替尼所致PAH(DASA-PAH)的易感因素,以对达沙替尼诱导的PAH(DASA-PAH)的高危患者进行分层。
本病例对照研究纳入了60例连续接受达沙替尼治疗的成年患者。当满足以下四项标准中的至少一项时,我们定义为DASA-PAH:(1)近期心电图改变提示右心室压力负荷过重;(2)经多普勒超声心动图测量估计收缩期肺动脉压>40 mmHg;(3)计算机断层扫描(CT)测量的肺动脉与主动脉直径比(PaD/AoD)>1;(4)经右心导管检查测量平均肺动脉压>25 mmHg且肺动脉楔压<15 mmHg。
在分析的59例患者中,我们确定了13例DASA-PAH患者。发生DASA-PAH的患者(PAH组)的基线PaD/AoD比值显著高于未发生的患者(非PAH组)。观察到达沙替尼治疗后PaD/AoD比值急剧上升。有趣的是,PAH组的EUTOS评分和脾脏大小明显小于非PAH组。
高基线PaD/AoD比值和低EUTOS评分与DASA-PAH的发生有关。脾脏可能对DASA-PAH起保护作用。