BCR-ABL1酪氨酸激酶抑制剂达沙替尼在慢性粒细胞白血病(CML)治疗中有效。达沙替尼的主要已知不良反应包括胸腔积液和肺动脉高压(PAH);然而,潜在机制尚不清楚.该病例报告描述了由心脏病专家和血液学家之间的多学科合作决定的两步达沙替尼剂量减少,以管理导致无治疗缓解(TFR)的PAH。这表明了该领域的一项重要改进。在这里,从2014年5月起,1名43岁的CML女性患者接受了每日100mg达沙替尼作为一线治疗.在开始服用达沙替尼之前,她的心电图和经胸超声心动图(TTE)没有明显异常。她在2015年6月出现了腿部水肿,TTE显示出较高的跨囊压力梯度值。基于这些发现,我们诊断为达沙替尼导致的PAH和右侧心力衰竭.然而,由于已确认分子反应(MR4.5)(国际规模:BCR-ABL1IS≤0.0032%)持续,在与心脏病学家进行了彻底讨论后,血液学家决定将达沙替尼剂量减少至70mg.剂量减少后,PAH立即改善;然而,在2017年再次观察到,第二次剂量减少至50mg后有所改善.此外,开始心血管药物治疗.PAH在2018年再次恶化,持续的MR4.5。因此,我们决定停用达沙替尼,因为MR4.5已持续超过4年.达沙替尼停药后,PAH再次改善,MR4.0(BCR-ABL1IS≤0.01%)水平已持续数年。此后,没有观察到PAH的明显恶化。我们介绍了一例可逆性达沙替尼诱导的PAH。通过几次剂量减少,可以成功治疗复发性PAH。并实现了TFR。这部分是由于血液学家和心脏病学家之间的有效合作。如果需要,在停用达沙替尼之前,可以考虑减少剂量作为治疗策略.
The BCR-ABL1 tyrosine kinase inhibitor dasatinib is effective in chronic myeloid leukemia (CML) treatment. The major known adverse effects of dasatinib include pleural effusion and pulmonary arterial hypertension (PAH); however, the underlying mechanisms remain unclear. This
case report describes a two-step dasatinib dose reduction decided by multi-disciplinary collaboration between cardiologists and hematologists for the management of PAH that led to treatment-free remission (TFR), suggesting an important improvement in the field. Herein, a 43-year-old woman with CML was administered 100 mg of dasatinib daily as a first-line therapy from May 2014. There were no evident abnormalities on her electrocardiogram and transthoracic echocardiography (TTE) charts before she started taking dasatinib. She developed leg edema in June 2015, and the TTE showed a high transtricuspid pressure gradient value. Based on these findings, we diagnosed PAH and right-sided heart failure due to dasatinib. However, since it was confirmed that the molecular response (MR4.5) (International Scale: BCR-ABL1IS ≤ 0.0032%) was sustained, the hematologist decided to reduce the dasatinib dose to 70 mg after thorough deliberations with the cardiologists. After the dose reduction, the PAH improved immediately; however, it was observed again in 2017, which improved with a second dose reduction to 50 mg. Additionally, cardiovascular drug therapy was initiated. The PAH was exacerbated again in 2018 with sustained MR4.5. Hence, we decided to discontinue dasatinib as the MR4.5 had been sustained over 4 years. After the discontinuation of dasatinib, PAH improved again, and near MR4.0 (BCR-ABL1IS ≤ 0.01%) level has been sustained for several years now. Thereafter, no apparent deterioration in PAH was observed. We present a
case of reversible dasatinib-induced PAH. Successful management of recurrent PAH was possible with several dose reductions, and TFR was achieved. This was partly due to effective collaboration between the hematologists and cardiologists. If needed, dose reduction as a treatment strategy may be considered before discontinuing dasatinib.