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.

中文翻译：

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尼罗替尼治疗在费城染色体阳性急性淋巴细胞白血病中诱导大颗粒淋巴细胞扩增并维持纵向缓解。

众所周知，第二代酪氨酸激酶抑制剂达沙替尼会引起免疫反应作为脱靶效应，并在 30% 的患者中诱导大颗粒淋巴细胞 (LGL) 扩增。然而，尼罗替尼治疗患者的 LGLs 扩增很少见。我们报告了一名 65 岁费城染色体 (Ph) 阳性急性淋巴细胞白血病 (ALL) 患者的病例，该患者在尼罗替尼治疗期间显示 LGLs 扩张。患者在多药化疗联合达沙替尼治疗后达到完全缓解（CR）。然而，当治疗因间质性肺炎而中断时，ALL 在中枢神经系统和骨髓中复发。随后开始尼罗替尼治疗，患者获得第二次 CR。尼罗替尼治疗开始后出现明显的外周血淋巴细胞增多。CD8 + CD57 + 细胞毒性 T 细胞主要扩增并显示出对 K562 Ph 阳性白血病细胞的强烈杀细胞活性。这些结果表明，与达沙替尼相似，尼罗替尼可诱导 LGLs 扩增，可能有助于 Ph-ALL 患者的长期缓解。