Takakuwa Teruhito, Sakai Ryota, Koh Shiro, Okamura Hiroshi, Nanno Satoru, Nakashima Yasuhiro, Nakane Takahiko, Koh Hideo, Hino Masayuki, Nakamae Hirohisa
Department of Hematology Graduate School of Medicine Osaka City University Osaka Japan.
Clin Case Rep. 2021 Jan 13;9(3):1344-1349. doi: 10.1002/ccr3.3770. eCollection 2021 Mar.
Tyrosine kinase inhibitor (TKI) can help to increase the survival time in chronic myeloid leukemia (CML) patients; however, the risk of secondary malignancies due to TKIs is a growing concern. Only few reports showed clinical course of patients who developed lymphoma during TKI therapies. Herein, we report a case of high-grade B-cell lymphoma diagnosed in the course of CML treatment with bosutinib. The 75-year-old male patient had been diagnosed with CML 25 years ago. After receiving TKIs (imatinib, nilotinib, and bosutinib), he achieved a major molecular response. Over 3 years after starting bosutinib, he was diagnosed with a high-grade B-cell lymphoma. A total of six courses of DA-EPOCH-R therapy brought complete remission of the lymphoma. Moreover, BCR-ABL1 transcript copies remained undetectable by RT-PCR, 8 months after stopping bosutinib. The risk of secondary malignancy due to TKI has been controversial. It is reported that TKI induces irreversible chromosomal abnormalities or chromosome aberrations and inhibits the proliferation or function of T cells, B cells, and NK cells. These mechanisms of TKI may contribute to the development of secondary malignancy. There remains no consensus on the management of secondary lymphoma during TKI therapies. At present, the only alternative is to observe patients receiving TKI treatment cautiously and to treat secondary lymphoma in the same manner as de novo lymphoma.
酪氨酸激酶抑制剂（TKI）有助于延长慢性髓性白血病（CML）患者的生存时间；然而，TKI导致继发性恶性肿瘤的风险日益受到关注。仅有少数报告显示了在TKI治疗期间发生淋巴瘤的患者的临床病程。在此，我们报告1例在使用博舒替尼治疗CML过程中诊断出的高级别B细胞淋巴瘤病例。该75岁男性患者于25年前被诊断为CML。在接受TKI（伊马替尼、尼洛替尼和博舒替尼）治疗后，他达到了主要分子反应。开始使用博舒替尼3年多后，他被诊断出患有高级别B细胞淋巴瘤。总共六个疗程的DA-EPOCH-R治疗使淋巴瘤完全缓解。此外，在停用博舒替尼8个月后，通过RT-PCR检测不到BCR-ABL1转录本拷贝。TKI导致继发性恶性肿瘤的风险一直存在争议。据报道，TKI会诱导不可逆的染色体异常或染色体畸变，并抑制T细胞、B细胞和NK细胞的增殖或功能。TKI的这些机制可能促使继发性恶性肿瘤的发生。对于TKI治疗期间继发性淋巴瘤的管理尚无共识。目前，唯一的选择是谨慎观察接受TKI治疗的患者，并以治疗原发性淋巴瘤的相同方式治疗继发性淋巴瘤。
