慢性B淋巴细胞增殖性疾病患者免疫化疗继发重症感染4例

Patients with Chronic B Cell Lymphocytic Proliferative Disorders Developing Severe Infections Secondary to Immunotherapy: Report of 4 Cases

摘要: B细胞慢性淋巴增殖性疾病(B-CLPD)是一组累及外周血/骨髓的成熟B细胞克隆增殖性疾病。B细胞慢性淋巴增殖性疾病可通过外周血/骨髓的形态学、免疫表型及细胞/分子遗传学检测进行诊断。这组疾病主要包括慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(CLL/SLL)、套细胞性淋巴瘤(MCL)及瓦尔登斯特伦巨球蛋白血症(WM)等。B细胞受体(BCR)信号通路的过度活化或异常与多种B细胞恶性肿瘤的发生、发展密切相关。自2015年以来，布鲁顿酪氨酸激酶(BTK)抑制剂先后获批应用于各种B细胞肿瘤，以BTK抑制剂为代表的新药一定程度上解决了传统免疫化疗对于遗传学高风险的患者、复发难治患者及不能耐受的老年患者疗效不佳这一问题。但B-CLPD患者在化疗联合BTK抑制剂时易发生感染，其中少见病原菌更存在诊断困难，早期诊断和积极治疗可获得较好的预后，本报道可为B-CLPD患者化疗联合免疫治疗过程中，尤其是BTK抑制剂应用时提供一定的经验借鉴。

Abstract: Chronic lymphoproliferative diseases of B cells (B-CLPD) are a group of clonal proliferative diseases of mature B cells involving peripheral blood/bone marrow. Chronic lymphoproliferative diseases of B cells can be diagnosed by morphological, immunophenotype and cytogenetic detection of peripheral blood/bone marrow. This group of diseases mainly includes chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL) and waldenstrom’s macroglobulinemia (WM). Overactivation or abnormality of B cell receptor (BCR) signaling pathway is closely related to the occurrence and development of various B cell malignant tumors. Since 2015, bruton tyrosine kinase (BTK) inhibitors have been approved to be used in various B-cell tumors. The new drugs represented by BTK inhibitors have solved the problem that traditional immunotherapy is not effective for patients with high genetic risk, patients with refractory recurrence and elderly patients who cannot tolerate it. However, patients with B-CLPD are prone to infection when chemotherapy combined with BTK inhibitors, among which rare pathogens are more difficult to diagnose. Early diagnosis and active treatment can obtain a better prognosis. This report can provide some experience for patients with B-CLPD in the process of chemotherapy combined with immunotherapy, especially when BTK inhibitors are used.