背景:嗜酸性粒细胞包括广泛的非血液学(继发性或反应性)和血液学(原发性或克隆性)疾病,可能导致终末器官损伤。
方法:嗜酸性粒细胞增多(HE)通常被定义为外周血嗜酸性粒细胞计数大于1.5×109/L,并可能与组织损伤有关。排除嗜酸性粒细胞增多的继发原因后,原发性嗜酸性粒细胞的诊断评估依赖于多种检查的组合.包括血液和骨髓的形态学检查,标准的细胞遗传学,荧光原位杂交,分子检测和血流免疫分型,以检测组织病理学或克隆性证据为急性或慢性血淋巴样肿瘤。
方法:疾病预后依赖于确定嗜酸性粒细胞增多亚型。在评估了嗜酸性粒细胞增多的继发原因后,2022年世界卫生组织和国际共识分类认可了疾病亚型的半分子分类方案.这包括主要类别“伴有嗜酸性粒细胞增多和酪氨酸激酶基因融合的骨髓/淋巴样肿瘤”(MLN-eo-TK),和MPN子类型,“慢性嗜酸性粒细胞白血病”(CEL)。淋巴细胞变体HE是一种异常的T细胞克隆驱动的反应性嗜酸性粒细胞,特发性嗜酸性粒细胞增多综合征(HES)是一种排除性诊断。
方法:治疗的目标是减轻嗜酸性粒细胞介导的器官损伤。对于嗜酸性粒细胞增多较温和形式的患者(例如,<1.5×109/L)无器官受累的症状或体征,可能会采取观察和等待的方法,并采取密切的后续行动。重排的PDGFRA或PDGFRB的鉴定是关键的,因为这些疾病对伊马替尼的精确反应性。Pemigatinib最近被批准用于复发或难治性FGFR1重排肿瘤患者。糖皮质激素是淋巴细胞变异型HE和HES患者的一线治疗。羟基脲和干扰素-α已证明作为初始治疗和在HES的类固醇难治性病例中的疗效。美泊利单抗,白细胞介素-5(IL-5)拮抗剂单克隆抗体,是由美国食品和药物管理局批准的特发性HES患者。细胞毒性化疗药物,造血干细胞移植已被用于侵袭性形式的HES和CEL,报告了数量有限的患者的结局。靶向治疗,如IL-5受体抗体benralizumab,IL-5单克隆抗体depemokimab,和MLN-eo-TK的各种酪氨酸激酶抑制剂,正在积极调查中。
BACKGROUND: The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with the potential for end-organ damage.
METHODS: Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 109/L, and may be associated with tissue damage. After the exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, molecular testing and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.
METHODS: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2022 World Health Organization and International
Consensus Classification endorse a semi-molecular classification scheme of disease subtypes. This includes the major category \"myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions\" (MLN-eo-TK), and the MPN subtype, \"chronic eosinophilic
leukemia\" (CEL). Lymphocyte-variant HE is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.
METHODS: The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g., <1.5 × 109/L) without symptoms or signs of organ involvement, a watch and wait approach with close follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1-rearranged neoplasms. Corticosteroids are first-line therapy for patients with lymphocyte-variant HE and HES. Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL-5 receptor antibody benralizumab, IL-5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN-eo-TK, are under active investigation.