Aslan Nevin Alayvaz, Hıncal Hande Oğul, Elver Özde, Erol Veysel, Güler Nil
Faculty of Medicine, Hematology Department, 52990Pamukkale University, Denizli, Turkey.
J Oncol Pharm Pract. 2023 Mar;29(2):511-516. doi: 10.1177/10781552221114070. Epub 2022 Jul 12.
The discovery of tyrosine kinase inhibitors provided a breakthrough in the treatment of chronic myeloid leukemia. Nowadays, the management of tyrosine kinase inhibitor-related side effects is one of the important problems in chronic myeloid leukemia treatment. Grades 3-4 pulmonary toxicity; especially pleural effusion is mostly seen with dasatinib treatment but rarely seen with nilotinib and bosutinib. Development of cross-intolerance due to pleural effusion is not an expected situation. Pleural effusion related to tyrosine kinase inhibitors is mostly exudative in nature with abundant lymphocytes.
Massive pleural effusion developed in a 59-year-old male patient with chronic myeloid leukemia, who was being treated with bosutinib. In the past, the patient had experienced massive pleural effusion also with dasatinib and nilotinib. The evaluation for differential diagnosis of pleural effusion did not reveal any additional malignancy.
After discontinuation of bosutinib and initiation of prednisolone, pleural effusion was totally resolved. Prednisolone was gradually discontinued and third-generation tyrosine kinase inhibitor ponatinib was started. After 12 months of follow-up, massive pleural effusion occurred again, leading to discontinuation of ponatinib.
Cross-intolerance is an important problem in the tyrosine kinase inhibitor era. The significance of this case is the development of cross-intolerance to all second-generation tyrosine kinase inhibitors and furthermore to a third-generation tyrosine kinase inhibitor. Management strategies for pleural effusion and close follow-up are important.
酪氨酸激酶抑制剂的发现为慢性髓性白血病的治疗带来了突破。如今，酪氨酸激酶抑制剂相关副作用的管理是慢性髓性白血病治疗中的重要问题之一。3-4级肺部毒性，尤其是胸腔积液，在达沙替尼治疗中最为常见，但在尼罗替尼和博舒替尼治疗中很少见。因胸腔积液导致交叉不耐受的情况并非预期出现的。与酪氨酸激酶抑制剂相关的胸腔积液本质上大多为渗出性，淋巴细胞丰富。
一名59岁慢性髓性白血病男性患者在接受博舒替尼治疗时出现大量胸腔积液。该患者过去使用达沙替尼和尼罗替尼时也曾出现大量胸腔积液。胸腔积液鉴别诊断评估未发现其他恶性肿瘤。
停用博舒替尼并开始使用泼尼松龙后，胸腔积液完全消退。泼尼松龙逐渐停用，开始使用第三代酪氨酸激酶抑制剂波纳替尼。随访12个月后，再次出现大量胸腔积液，导致波纳替尼停用。
交叉不耐受是酪氨酸激酶抑制剂时代的一个重要问题。该病例的意义在于对所有第二代酪氨酸激酶抑制剂以及第三代酪氨酸激酶抑制剂均出现交叉不耐受。胸腔积液的管理策略及密切随访很重要。
