Minami Mariko, Arita Takeshi, Iwasaki Hiromi, Muta Tsuyoshi, Aoki Takatoshi, Aoki Kenichi, Yamasaki Satoshi, Matsushima Takamitsu, Kato Koji, Takenaka Katsuto, Tanimoto Kazuki, Kamimura Tomohiko, Ogawa Ryosuke, Akashi Koichi, Miyamoto Toshihiro
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Department of Haematology, National Kyushu Medical Centre, Fukuoka, Japan.
Br J Haematol. 2017 May;177(4):578-587. doi: 10.1111/bjh.14608. Epub 2017 Mar 24.
Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long-term TKI treatment.
肺动脉高压(PH)是接受酪氨酸激酶抑制剂(TKI)治疗的患者中一种罕见但危及生命的不良事件,如达沙替尼,但在接受伊马替尼或尼洛替尼治疗的患者中尚未得到充分评估。我们使用超声心动图对105例接受伊马替尼(n = 37)、尼洛替尼(n = 30)或达沙替尼(n = 38)治疗的慢性髓性白血病(CML)患者进行无创评估,以确定PH的发生率。反映肺动脉压的平均三尖瓣反流峰值梯度(TRPG)在伊马替尼组为22.7 mmHg,尼洛替尼组为23.1 mmHg,达沙替尼组为23.4 mmHg。这些值无显著差异,但高于新诊断的CML患者(19.0 mmHg)。在105例患者中有9例检测到TRPG>31 mmHg,标志着可能出现PH:1例(2.7%)接受伊马替尼治疗,3例(10.0%)接受尼洛替尼治疗,5例(13.2%)接受达沙替尼治疗。只有3例患者主诉呼吸困难,而其他6例无症状。此外,TRPG值与年龄或TKI治疗持续时间存在相关性趋势。这些结果表明,不仅达沙替尼,而且伊马替尼和尼洛替尼治疗都可能与亚临床PH相关。无创超声心动图有助于筛查,尤其是在长期接受TKI治疗的老年患者中。