Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong 50, Gangnam-gu, Seoul, Korea.
Am J Hematol. 2011 Apr;86(4):346-50. doi: 10.1002/ajh.21980.
The current retrospective study investigated the incidence of lymphocytosis following second-line dasatinib therapy in chronic myeloid leukemia (CML) and analyzed the clinical factors predictive of the development of lymphocytosis, as well as association with treatment outcomes. Fifty CML patients who failed imatinib treatment and received dasatinib were included from nine centers in the Republic of Korea. The cumulative incidence of lymphocytosis was assessed, and cytogenetic and molecular response, treatment failure, loss of response, progression to advanced disease, and survival were evaluated and analyzed according to the development of lymphocytosis. After a median of 17 months of dasatinib therapy, 23 patients (46%) developed lymphocytosis (median onset 4 months). No clinical predictive factor for the development of lymphocytosis was found. The group presenting lymphocytosis showed a higher complete cytogenetic response (CCyR; 78.3 vs. 29.6%, P = 0.001) and major molecular response (MMR; 52.2 vs. 14.8%, P = 0.005), in comparison to the group without presenting lymphocytosis. The development of lymphocytosis after dasatinib was identified as a favorable independent marker for predicting a CCyR (P = 0.002) or MMR (P = 0.003). Further study is necessary to identify which subset of lymphocytes was expanded and to reveal the exact mechanism by which dasatinib induces lymphocyte expansion.
本回顾性研究调查了二线达沙替尼治疗慢性髓性白血病 (CML) 后发生淋巴细胞增多的发生率，并分析了预测淋巴细胞增多发展的临床因素，以及与治疗结果的关联。从韩国的九个中心纳入了 50 名因伊马替尼治疗失败而接受达沙替尼治疗的 CML 患者。评估淋巴细胞增多的累积发生率，并根据淋巴细胞增多的发展评估和分析细胞遗传学和分子反应、治疗失败、无反应丧失、进展为晚期疾病以及生存情况。在达沙替尼治疗的中位数为 17 个月后，23 名患者（46%）发生淋巴细胞增多（中位数发病时间为 4 个月）。未发现淋巴细胞增多发展的临床预测因素。与未出现淋巴细胞增多的患者相比，出现淋巴细胞增多的患者表现出更高的完全细胞遗传学缓解（CCyR；78.3% vs. 29.6%，P=0.001）和主要分子缓解（MMR；52.2% vs. 14.8%，P=0.005）。达沙替尼后发生淋巴细胞增多被确定为预测 CCyR（P=0.002）或 MMR（P=0.003）的有利独立标志物。需要进一步研究以确定哪种淋巴细胞亚群被扩增，并揭示达沙替尼诱导淋巴细胞扩增的确切机制。
