Leukocytosis, monocytosis, and eosinophilia in systemic mastocytosis: analysis of phenotype, genetics and prognosis in 596 patients from the GREM registry.

IF 6.6 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology-In Practice Pub Date : 2025-09-24 DOI:10.1016/j.jaip.2025.09.018

Johannes Lübke, Nicole Naumann, Vito Dangelo, Alice Fabarius, Georgia Metzgeroth, Hans-Peter Horny, Karl Sotlar, Wolf-Karsten Hofmann, Martina Rudelius, Juliana Schwaab, Andreas Reiter

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引用次数: 0

Abstract

Background: Leukocytosis, monocytosis, and eosinophilia (L/M/E) are recurrent findings in systemic mastocytosis (SM).

Objective: To investigate the prevalence of L/M/E in SM and assess their association with clinical phenotype, mutational profile, and overall survival (OS) in advanced SM (AdvSM).

Methods: Within the German Registry on Disorders of Eosinophilia and Mast Cells (GREM), 596 SM patients (91% KIT D816V positive; 270 AdvSM, 326 non-AdvSM) were analyzed for L/M/E.

Results: In comparison to non-AdvSM, AdvSM patients had significantly higher leukocyte (median 9.4 vs. 6.9×10⁹/L), monocyte (median 0.7 vs. 0.5×10⁹/L), and eosinophil counts (median 0.3 vs. 0.1×10⁹/L; all P<0.001) with highest counts (leukocytes: 10.2×10⁹/L, monocytes: 0.9×10⁹/L, eosinophils: 0.3×10⁹/L; all P<0.001) being observed in SM with associated hematologic neoplasm (SM-AHN). High counts of L/M/E correlated with an increased number of additional somatic mutations (P=0.012, P<0.001, P=0.020) with monocytosis being specially associated with mutations in ASXL1 (odds ratio [OR] 2.91; 95% CI: 1.5-5.8), SRSF2 (OR 2.2; 95% CI: 1.2-4.0), and TET2 (OR 2.2; 95% CI: 1.2-4.0). In AdvSM, optimal OS cut-off values based on maximally selected rank statistics were ≥16.8×10⁹/L for leukocytosis (median OS: 1.6 vs. 4.7 years, P<0.001), ≥1.1×10⁹/L for monocytosis (2.9 vs. 4.8 years, P<0.001), and ≥1.5×10⁹/L for eosinophilia (1.7 vs. 5.0 years, P<0.001). Monocytosis and/or eosinophilia defined a three-tiered risk model (median OS: 1.60 vs. 3.04 vs. 6.94 years, P<0.001).

Conclusions: Elevated counts of L/M/E are indicative of AdvSM and within AdvSM associated with additional somatic mutations, a subtype of SM-AHN and poor prognosis.

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系统性肥大细胞增多症中的白细胞增多症、单核细胞增多症和嗜酸性粒细胞增多症：来自GREM登记的596例患者的表型、遗传学和预后分析。

背景：白细胞增多症、单核细胞增多症和嗜酸性粒细胞增多症（L/M/E）是系统性肥大细胞增多症（SM）的反复表现。目的：探讨L/M/E在SM中的患病率，并评估其与晚期SM （AdvSM）临床表型、突变谱和总生存期（OS）的关系。方法：在德国嗜酸性粒细胞增多和肥大细胞疾病登记处（GREM）中，对596例SM患者（91%的KIT D816V阳性；270例AdvSM， 326例非AdvSM）进行L/M/E分析。结果：与非AdvSM相比，AdvSM患者的白细胞（中位数为9.4 vs. 6.9×109/L）、单核细胞（中位数为0.7 vs. 0.5×109/L）和嗜酸性粒细胞计数(中位数为0.3 vs. 0.1×109/L；所有P9/L，单核细胞：0.9×109/L，嗜酸性粒细胞：0.3×109/L；白细胞增多症的P9/L(中位OS: 1.6 vs. 4.7年，单核细胞增多症的P9/L （2.9 vs. 4.8年），嗜酸性粒细胞增多症的P9/L （1.7 vs. 5.0年）。结论：L/M/E计数升高表明AdvSM和AdvSM内与额外的体细胞突变、SM-AHN亚型和不良预后相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Allergy and Clinical Immunology-In Practice ALLERGYIMMUNOLOGY-IMMUNOLOGY

CiteScore

11.10

自引率

9.60%

发文量

683

审稿时长

50 days

期刊介绍： JACI: In Practice is an official publication of the American Academy of Allergy, Asthma & Immunology (AAAAI). It is a companion title to The Journal of Allergy and Clinical Immunology, and it aims to provide timely clinical papers, case reports, and management recommendations to clinical allergists and other physicians dealing with allergic and immunologic diseases in their practice. The mission of JACI: In Practice is to offer valid and impactful information that supports evidence-based clinical decisions in the diagnosis and management of asthma, allergies, immunologic conditions, and related diseases. This journal publishes articles on various conditions treated by allergist-immunologists, including food allergy, respiratory disorders (such as asthma, rhinitis, nasal polyps, sinusitis, cough, ABPA, and hypersensitivity pneumonitis), drug allergy, insect sting allergy, anaphylaxis, dermatologic disorders (such as atopic dermatitis, contact dermatitis, urticaria, angioedema, and HAE), immunodeficiency, autoinflammatory syndromes, eosinophilic disorders, and mast cell disorders. The focus of the journal is on providing cutting-edge clinical information that practitioners can use in their everyday practice or to acquire new knowledge and skills for the benefit of their patients. However, mechanistic or translational studies without immediate or near future clinical relevance, as well as animal studies, are not within the scope of the journal.