Laboratory Assessment of Patients with Hypereosinophilic Syndrome

除了FIP1L1-PDGFRA融合基因的存在外，对临床定义的高嗜酸性粒细胞综合征(HES)中伊马替尼反应的预测因素知之甚少。 在这项研究中，我们根据HES患者的FIP1L1-PDGFRA突变状态和提示髓系肿瘤的标准对HES患者进行分层。外周血和骨髓标本进行外周血和骨髓涂片(异常分叶、不均匀颗粒化、低颗粒化、颗粒化)、血清B12水平1000pg/ml、血清类胰蛋白酶水平12 ng/ml、贫血和/或血小板减少、骨髓细胞数和GT；80%成熟左移、骨髓活检异常(纺锤形)肥大细胞、骨髓活检网状蛋白BroSis 2+和骨髓活检异常巨核细胞的检测。 受试者中有FIP1L1-PDGFRA-髓系肿瘤(FP；n=12)，PDGFRA阴性的HES(MHEs；n=10)，或激素难治性PDGFRA阴性的HES(SR；n=5)，伊马替尼治疗。主要结果是1个月时嗜酸性粒细胞计数<1.5×109/L，临床症状改善。对伊马替尼的临床、分子和骨髓反应进行了评估。此外，根据前瞻性研究中使用的标准，对18名临床明确的HES患者进行了回顾性队列研究，这些患者接受伊马替尼(每天300-400 mg，每天1个月)治疗。 结果显示，伊马替尼在FP组(n=16)、MHEs组(n=13)和SR组(n=16)的有效率分别为100%、54%和0%。4个髓系特征的存在是唯一预测疗效的因素。在完全缓解18个月后，8名FP和1名MHEs患者逐渐减少并停用伊马替尼。7名受试者(6名FP，1名MHEs)继续接受缓解治疗，中位数为29个月(14-36个月)。 总之，MHEs的临床特征可以预测PDGFRA阴性的HES患者对伊马替尼的反应。

With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES). In this study, we have stratified HES patients according to their FIP1L1-PDGFRA mutational status and criteria suggestive of a myeloid neoplasm. The peripheral blood and bone marrow specimens were evaluated for dysplastic eosinophils on peripheral smear (abnormal nuclear lobation, uneven granulation, hypogranulation, agranulation), serum B12 level 1000 pg/ml, serum tryptase level 12 ng/mL, anemia and/or thrombocytopenia, bone marrow cellularity >80% with left shift in maturation, dysplastic (spindle-shaped) mast cells on bone marrow biopsy, evidence of reticulin brosis 2+ on bone marrow biopsy, and dysplastic megakaryocytes on bone marrow biopsy. Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with 4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy. The primary outcome was an eosinophil count <1.5 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. In addition, a retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily 1 month) were classified according to the criteria used in the prospective study. Overall results showed that imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of 4 myeloid features was the sole predictor of response. After 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remained in remission off therapy for a median of 29 months (range 14-36). In conclusion, clinical features of MHES predict imatinib response in PDGFRA-negative HES.