Maral Senem, Bakanay Sule Mine, Kucuksahin Orhan, Dilek Imdat
Department of Hematology, Dıskapı Yıldırım Beyazıt Research and Training Hospital, Ankara, Turkey.
Department of Hematology, Ataturk Research and Training Hospital, Ankara, Turkey.
J Oncol Pharm Pract. 2020 Apr;26(3):738-741. doi: 10.1177/1078155219863469. Epub 2019 Jul 30.
Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib.
A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE).
Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse.
Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.
达沙替尼是一种强效酪氨酸激酶抑制剂，用于治疗慢性髓性白血病。胸腔积液是患者在达沙替尼治疗期间常见的副作用。肺动脉高压是达沙替尼罕见且危及生命的不良事件。达沙替尼与自身免疫性疾病之间的关系尚不清楚，但有报道称存在达沙替尼引发自身免疫的可能机制。
一名53岁男性被诊断为慢性髓性白血病，并开始使用甲磺酸伊马替尼进行治疗。由于患者在治疗的第一年无反应，伊马替尼被更换为达沙替尼。在达沙替尼治疗的第四年，慢性髓性白血病达到血液学和细胞遗传学缓解时，患者出现双侧大量渗出性胸腔积液。超声心动图显示符合心包积液，右心室扩大，左侧心功能正常。诊断为肺动脉高压，收缩期肺动脉压升高。当他出现发热和关节痛时，进一步检查显示抗核抗体（滴度1/160）和抗RNP/Sm呈阳性，这对系统性红斑狼疮（SLE）的诊断具有高特异性。
停用达沙替尼并开始使用尼洛替尼。尽管使用利尿剂和甲泼尼龙，胸腔积液仍持续存在，因此开始使用霉酚酸酯作为一种减少类固醇用量的免疫抑制剂。狼疮样症状消失，停用达沙替尼后抗体检测不到。心包积液改善，胸腔积液未复发。
对于有自身免疫性疾病病史或症状的患者，在开始使用达沙替尼之前可能建议进行自身抗体筛查。所有在达沙替尼治疗期间出现胸腔积液的患者都应进行狼疮抗体检查。
