Sicuranza Anna, Ferrigno Ilaria, Abruzzese Elisabetta, Iurlo Alessandra, Galimberti Sara, Gozzini Antonella, Luciano Luigiana, Stagno Fabio, Russo Rossi Antonella, Sgherza Nicola, Cattaneo Daniele, Zuanelli Brambilla Corrado, Marzano Cristina, Fava Carmen, Mulas Olga, Cencini Emanuele, Santoni Adele, Sammartano Vincenzo, Gozzetti Alessandro, Puccetti Luca, Bocchia Monica
Hematology Unit, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy.
S. Eugenio Hospital, Tor Vergata University, Rome, Italy.
Front Oncol. 2022 Feb 1;12:835563. doi: 10.3389/fonc.2022.835563. eCollection 2022.
Tyrosine kinase inhibitors (TKI) may offer a normal life expectancy to Chronic Myeloid Leukemia (CML) patients. However, a higher than expected incidence of arterial occlusive events (AOEs) was observed during treatment with nilotinib. We previously showed an "inflammatory status" during nilotinib that may explain the increased incidence of AOEs. Thus, we conducted this prospective KIARO study involving 186 CML patients (89 imatinib, 59 nilotinib, 38 dasatinib). Interleukin 6 (IL6), interleukin 10 (IL10), Tumor Necrosis Factor-α (TNFα), oxLDL, and high-sensitivity C-reactive protein (hs-CRP) plasma levels were measured at diagnosis and during treatment, with the aim to investigate changes in the inflammatory status favoring AOEs of each patient. Clinical and biochemical pro-atherothrombotic profiles and the 10-year SCORE chart were also evaluated. We showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib, as demonstrated by higher hs-CRP and oxLDL levels and increased IL6/IL10 and TNFα/IL10 ratios only in nilotinib cohort. After median follow-up of 23.3 months starting from TKI, 10/186 patients (5.4%) suffered an AOE. Approximately 5/10 (50%) AOEs occurred during nilotinib treatment despite a lower 10-year SCORE and a lower median age in this subgroup. A longer follow-up is needed to further confirm the active role of nilotinib in AOEs pathogenesis.
酪氨酸激酶抑制剂（TKI）可能使慢性髓性白血病（CML）患者拥有正常的预期寿命。然而，在使用尼洛替尼治疗期间，观察到动脉闭塞事件（AOE）的发生率高于预期。我们之前发现尼洛替尼治疗期间存在“炎症状态”，这可能解释了AOE发生率增加的原因。因此，我们开展了这项前瞻性KIARO研究，纳入了186例CML患者（89例使用伊马替尼，59例使用尼洛替尼，38例使用达沙替尼）。在诊断时和治疗期间测量了白细胞介素6（IL6）、白细胞介素10（IL10）、肿瘤坏死因子-α（TNFα）、氧化型低密度脂蛋白（oxLDL）和高敏C反应蛋白（hs-CRP）的血浆水平，旨在研究有利于每位患者发生AOE的炎症状态变化。还评估了临床和生化促动脉粥样硬化血栓形成特征以及10年SCORE图表。我们发现，与伊马替尼或达沙替尼相比，尼洛替尼治疗期间促炎/促氧化环境增加，仅在尼洛替尼队列中hs-CRP和oxLDL水平升高以及IL6/IL10和TNFα/IL10比值增加证明了这一点。从开始使用TKI进行中位随访23.3个月后，186例患者中有10例（5.4%）发生了AOE。尽管该亚组的10年SCORE较低且中位年龄较低，但约5/10（50%）的AOE发生在尼洛替尼治疗期间。需要更长时间的随访来进一步证实尼洛替尼在AOE发病机制中的积极作用。
