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尼罗替尼治疗诱导费城染色体阳性急性淋巴细胞白血病的大颗粒淋巴细胞扩增和维持纵向缓解。

Nilotinib treatment induced large granular lymphocyte expansion and maintenance of longitudinal remission in a Philadelphia chromosome-positive acute lymphoblastic leukemia.

机构信息

Department of Hematology, Eiju General Hospital, 2-23-16 Higashi-Ueno, Taito-ku, Tokyo, 110-8645, Japan.

Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.

出版信息

Int J Hematol. 2020 May;111(5):719-723. doi: 10.1007/s12185-019-02789-6. Epub 2020 Jan 1.

Abstract

It is well known that the second-generation tyrosine kinase inhibitor dasatinib evokes an immunological reaction as an off-target effect and induces large granular lymphocytes (LGLs) expansion in 30% of patients. However, LGLs expansion in nilotinib-treated patients is rare. We report the case of a 65-year-old patient with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) who showed LGLs expansion during nilotinib treatment. The patient achieved complete remission (CR) after multi-agent chemotherapy combined with dasatinib treatment. However, ALL relapsed in the central nervous system and bone marrow when treatment was interrupted due to interstitial pneumonia. Nilotinib treatment was subsequently started and the patient achieved second CR. Marked peripheral blood lymphocytosis emerged after the start of nilotinib treatment. CD8 + CD57 + cytotoxic T cells were predominantly expanded and showed strong cytocidal activity against K562 Ph-positive leukemia cells. These results suggest that similar to dasatinib, nilotinib can induce LGLs expansion, possibly contributing to long-term remission in patients with Ph-ALL.

摘要

众所周知,第二代酪氨酸激酶抑制剂达沙替尼会产生免疫反应,这是一种脱靶效应,并导致 30%的患者出现大颗粒淋巴细胞 (LGL) 扩增。然而,尼洛替尼治疗患者的 LGL 扩增很少见。我们报告了一例 65 岁费城染色体阳性急性淋巴细胞白血病 (Ph-ALL) 患者,在尼洛替尼治疗期间出现 LGL 扩增。该患者在接受多药物化疗联合达沙替尼治疗后达到完全缓解 (CR)。然而,由于间质性肺炎导致治疗中断,中枢神经系统和骨髓中的 ALL 复发。随后开始尼洛替尼治疗,患者达到第二次 CR。尼洛替尼治疗开始后,外周血出现明显的淋巴细胞增多。CD8+CD57+cytotoxic T 细胞明显扩增,并对 K562 Ph 阳性白血病细胞表现出强烈的细胞毒性作用。这些结果表明,尼洛替尼与达沙替尼类似,可诱导 LGL 扩增,可能有助于 Ph-ALL 患者的长期缓解。

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