Autore Francesco, Pasquale Raffaella, Innocenti Idanna, Fresa Alberto, Sora' Federica, Laurenti Luca
Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy.
Cancers (Basel). 2021 Nov 19;13(22):5804. doi: 10.3390/cancers13225804.
Chronic lymphocytic leukemia (CLL) patients have a greater predisposition to develop autoimmune complications. The most common of them is autoimmune hemolytic anemia (AIHA) with a frequency of 7-10% of cases. Pathogenesis is multifactorial involving humoral, cellular, and innate immunity. CLL B-cells have damaged apoptosis, produce less immunoglobulins, and could be responsible for antigen presentation and releasing inflammatory cytokines. CLL B-cells can act similar to antigen-presenting cells activating self-reactive T helper cells and may induce T-cell subsets imbalance, favoring autoreactive B-cells which produce anti-red blood cells autoantibodies. Treatment is individualized and it depends on the presence and severity of clinical symptoms, disease status, and comorbidities. Corticosteroids are the standardized first-line treatment; second-line treatment comprises rituximab. Patients not responding to corticosteroids and rituximab should be treated with CLL-specific drugs as per current guidelines according to age and comorbidities. New targeted drugs (BTK inhibitors and anti BCL2) are recently used after or together with steroids to manage AIHA. In the case of cold agglutinin disease, rituximab is preferred, because steroids are ineffective. Management must combine supportive therapies, including vitamins; antibiotics and heparin prophylaxis are indicated in order to minimize infectious and thrombotic risk.
慢性淋巴细胞白血病（CLL）患者更易发生自身免疫性并发症。其中最常见的是自身免疫性溶血性贫血（AIHA），发生率为7%-10%。其发病机制是多因素的，涉及体液免疫、细胞免疫和固有免疫。CLL B细胞凋亡受损，产生的免疫球蛋白较少，可能负责抗原呈递和释放炎性细胞因子。CLL B细胞的作用类似于抗原呈递细胞，可激活自身反应性T辅助细胞，并可能导致T细胞亚群失衡，有利于产生抗红细胞自身抗体的自身反应性B细胞。治疗是个体化的，取决于临床症状的存在和严重程度、疾病状态及合并症。皮质类固醇是标准化的一线治疗药物；二线治疗包括利妥昔单抗。对皮质类固醇和利妥昔单抗无反应的患者应根据年龄和合并症，按照现行指南使用CLL特异性药物进行治疗。最近，新型靶向药物（BTK抑制剂和抗BCL2药物）在使用类固醇之后或与类固醇联合使用，以治疗AIHA。对于冷凝集素病，首选利妥昔单抗，因为类固醇无效。治疗必须结合支持性疗法，包括补充维生素；使用抗生素和预防性使用肝素，以将感染和血栓形成风险降至最低。
