Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.
Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.
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伊鲁替尼和其他靶向b细胞受体信号抑制剂对慢性淋巴细胞白血病（CLL）患者取得了令人印象深刻的临床效果。治疗诱导的绝对淋巴细胞计数（ALC）的上升已成为CLL中激酶抑制剂的一类效应，值得进一步研究。我们在此报告64例接受依鲁替尼治疗的CLL患者的相关研究。我们量化了血液、淋巴结、脾脏和骨髓中的肿瘤负荷，评估了循环细胞的表型变化，并测量了全血粘度。仅使用一剂依鲁替尼，ALC平均增加66%，超过40%的患者ALC在开始治疗后24小时内达到峰值。第2天循环的CLL细胞显示Ki67和CD38表达增加，表明肿瘤细胞从组织室外排到血液中。治疗引起的淋巴细胞增多的动力学和程度是高度可变的；有趣的是，在基线ALC高的患者中，相对增加是轻微的，并且消退迅速。治疗两个周期后，无论ALC的相对变化如何，淋巴结、骨髓和脾脏的疾病负担均有所减轻。全血粘度依赖于ALC和血红蛋白。没有不良事件归因于淋巴细胞增多。
Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further investigation. We here report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes, spleen, and bone marrow, assessed phenotypic changes of circulating cells, and measured whole blood viscosity. With just one dose of ibrutinib the average increase in ALC was 66%, and in over 40% of patients the ALC peaked within 24 hours of initiating treatment. Circulating CLL cells on day 2 showed increased Ki67 and CD38 expression, indicating an efflux of tumor cells from the tissue compartments into the blood. The kinetics and degree of the treatment-induced lymphocytosis was highly variable; interestingly in patients with a high baseline ALC the relative increase was mild and resolution rapid. After two cycles of treatment the disease burden in lymph node, bone marrow, and spleen decreased irrespective of the relative change in ALC. Whole blood viscosity was dependent on both ALC and hemoglobin. No adverse events were attributed to the lymphocytosis.
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淋巴结微环境促进慢性淋巴细胞白血病的 B 细胞受体信号转导、NF-κB 激活和肿瘤增殖
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