Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia; Diagnostic Haematology, The Royal Melbourne Hospital, Parkville, Vic, Australia.
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia.
Pathology. 2021 Aug;53(5):608-612. doi: 10.1016/j.pathol.2020.10.023. Epub 2021 Feb 19.
We reviewed haematological investigations for 43 patients treated at a single centre with alectinib, an inhibitor of anaplastic lymphoma kinase (ALK) which is considered standard first-line treatment for patients with ALK-rearranged advanced non-small cell lung cancer. Ninety-five percent of patients developed marked acanthocytosis, echinocytosis and/or spheroacanthocytosis, not observable with prior treatment with other ALK-inhibitors. Anaemia developed in 73% of patients (38% <100 g/L, 8% <80 g/L), though definite new haemolysis was present in only 11%. Eosin-5-maleimide binding was reduced in all assessed patients, and increased membrane cholesterol was identified in one patient assessed with lattice light sheet microscopy. We have identified a previously undescribed phenomenon whereby alectinib induces red cell membrane abnormalities in nearly all patients through an unclear, but likely ALK-independent, mechanism, resulting in mild anaemia without universal haemolysis.
我们回顾了在单一中心接受艾乐替尼治疗的 43 名患者的血液学检查结果，艾乐替尼是一种间变性淋巴瘤激酶 (ALK) 的抑制剂，被认为是 ALK 重排的晚期非小细胞肺癌患者的标准一线治疗药物。95%的患者出现明显的棘红细胞增多症、刺状红细胞增多症和/或球形棘红细胞增多症，而之前使用其他 ALK 抑制剂治疗时则观察不到这些现象。73%的患者出现贫血（38% <100 g/L，8% <80 g/L），尽管只有 11%的患者出现明确的新溶血性贫血。所有评估的患者的伊文思蓝 5-马来酰亚胺结合均减少，并且在用晶格光片显微镜评估的一名患者中发现了增加的膜胆固醇。我们已经确定了一种以前未描述的现象，即艾乐替尼通过一种尚不清楚但可能与 ALK 无关的机制，几乎在所有患者中引起红细胞膜异常，导致轻度贫血而无普遍溶血。
