Yu Tian, Li Weiming, Yu Tao
Department of Hematology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China.
College of Basic Medical Sciences, China Three Gorges University, Yichang, China.
Front Oncol. 2023 Aug 3;13:1217023. doi: 10.3389/fonc.2023.1217023. eCollection 2023.
The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and COVID-19. The underlying mechanism may be related to the inhibition of the immune function by TKI. Poor management, including disease progression due to the infectious disease or TKI dose reduction or discontinuation, may lead to adverse clinical outcomes and can even be life-threatening. Therefore, this review principally provides an overview of the pathogenesis and standardized management principles of CML patients with comorbid COVID-19 or hepatitis B in order to improve clinicians' awareness of the risks so as to more effectively diagnose and treat CML and improve the survival rate and quality of life of patients. In the past two decades, owing to the advent of imatinib, chronic myeloid leukemia (CML) has transformed into a chronic controllable disease, and even treatment-free remission can be anticipated. Earlier studies have indicated that tyrosine kinase inhibitor (TKI) exerts a peculiar inhibitory effect on the body's immune function. Therefore, with the widespread application of TKI, more and more attention has been paid to the comorbidity of infectious diseases in CML patients, especially in patients with progressive disease or non-remission. Despite some studies revealing that the proportion and severity of SARS-CoV-2 infection in CML patients receiving TKI treatment are lower than in patients with other hematological malignancies, CML patients with stable disease are still recommended to be vaccinated against SARS-CoV-2, while TKI may or may not be discontinued. Meanwhile, the management of CML patients during the epidemic of coronavirus disease 2019 (COVID-19) still necessitates further discussion. This article also provides an overview of TKI-related hepatitis B reactivation. If not managed, patients may face adverse consequences such as hepatitis B reactivation-related hepatitis, liver failure, and progression of CML after forced withdrawal of medication. Therefore, this review aimed to comprehensively describe the management of CML patients with comorbid COVID-19, the pathogenesis of hepatitis B reactivation, the indicated population for prophylactic antiviral therapy, the time of antiviral drug discontinuation, and drug selection.
免疫抑制剂和靶向药物的应用为血液系统肿瘤的治疗开辟了新途径,酪氨酸激酶抑制剂用于治疗慢性髓性白血病是一项具有里程碑意义的突破,显著改善了慢性髓性白血病患者的预后。然而,随着酪氨酸激酶抑制剂的广泛使用,慢性髓性白血病患者的合并感染问题日益凸显,尤其是在乙型肝炎和新型冠状病毒肺炎等传染病方面。其潜在机制可能与酪氨酸激酶抑制剂对免疫功能的抑制有关。管理不善,包括因传染病导致疾病进展或酪氨酸激酶抑制剂剂量减少或停药,可能导致不良临床后果,甚至危及生命。因此,本综述主要概述了合并新型冠状病毒肺炎或乙型肝炎的慢性髓性白血病患者的发病机制和规范化管理原则,以提高临床医生对风险的认识,从而更有效地诊断和治疗慢性髓性白血病,提高患者的生存率和生活质量。在过去二十年中,由于伊马替尼的出现,慢性髓性白血病已转变为一种可慢性控制的疾病,甚至有望实现无治疗缓解。早期研究表明,酪氨酸激酶抑制剂对机体免疫功能具有独特的抑制作用。因此,随着酪氨酸激酶抑制剂的广泛应用,慢性髓性白血病患者合并感染性疾病的问题越来越受到关注,尤其是在疾病进展或未缓解的患者中。尽管一些研究表明,接受酪氨酸激酶抑制剂治疗的慢性髓性白血病患者感染新型冠状病毒的比例和严重程度低于其他血液系统恶性肿瘤患者,但仍建议病情稳定的慢性髓性白血病患者接种新型冠状病毒疫苗,同时酪氨酸激酶抑制剂可能需要停药,也可能不需要停药。与此同时,2019冠状病毒病(新型冠状病毒肺炎)疫情期间慢性髓性白血病患者的管理仍需进一步探讨。本文还概述了酪氨酸激酶抑制剂相关的乙型肝炎再激活。如果不进行管理,患者可能面临如乙型肝炎再激活相关肝炎、肝衰竭以及停药后慢性髓性白血病进展等不良后果。因此,本综述旨在全面描述合并新型冠状病毒肺炎的慢性髓性白血病患者的管理、乙型肝炎再激活的发病机制、预防性抗病毒治疗的适用人群、抗病毒药物停药时间以及药物选择。