World Health Organization‐defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management

Abstract

Disease Overview: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary or clonal) disorders with potential for end-organ damage.Diagnosis: Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 Â 10 9 /L. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, next generation sequencing gene assays, and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.Risk Stratification: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2", and the myeloproliferative neoplasm subtype, "chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant HE is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion. Risk-adapted Therapy:The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (eg, < 1.5 Â 10 9 /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. 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, was recently approved by the US Food and Drug Administration for patients with idiopathic HES. The use of the IL-5 receptor antibody benralizumab, as well as other targeted therapies such as JAK2 and FGFR1 inhibitors, is under active investigation.

Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome

“…Many patients with HES continue to experience disease flares despite receiving standard of care therapies such as OCS, IS, CT, or other therapies ( 2 , 6 ). This post hoc analysis demonstrates the add-on benefit of mepolizumab on top of existing treatments as mepolizumab was associated with a lower occurrence of flares versus placebo across all baseline therapy groups.…”

“…The disease course is also heterogeneous, with different patterns of relapse and disease activity, and patients may experience flares, a worsening of HES-related disease activity requiring an increase in treatment ( 3 ). As disease outcomes in HES are linked to the nature and extent of end-organ damage ( 4 , 5 ), treatment goals focus on the prevention and reversal of organ damage to improve symptoms by reducing eosinophilic inflammation ( 6 ).…”

“…For example, patients who are positive for the fusion gene FIP1L1-PDGFRA respond effectively to imatinib (tyrosine kinase inhibitor) treatment ( 2 , 6 ). However, current standard of care treatment for patients with HES without the FIP1L1-PDGFRA fusion gene or other tyrosine kinase rearrangements is less effective and includes oral corticosteroids (OCS) as a first-line treatment often used with immunosuppressive and/or cytotoxic (IS/CT) therapies, commonly hydroxycarbamide or interferon-α ( 2 , 6 ). Depending on the pattern of the disease course, treatments may be used chronically or for the treatment of flares as required ( 3 ).…”

Analysis of the Clinical Significance and Safety of Interferon in the Treatment of Chronic Myeloproliferative Tumors

“…All these suggest that IFN treatment of patients with chronic MPN can effectively improve the long-term PFS of patients [ 19 ]. Moreover, the incidences of thrombotic events, splenomegaly, and myelofibrosis in patients treated with IFN were significantly lower than in those treated with HU [ 20 ]. The adverse reactions of patients treated with IFN are mainly flu-like symptoms, which are relieved after discontinuation of treatment or application of symptomatic drug treatment that is tolerated by most patients.…”

Eosinophilia and Lung Cancer: Analysis From Real-World Data and Mendelian Randomization Study

“…Eosinophils are a type of white blood cell formed from stem cells in the bone marrow. Although normal numbers of eosinophils in the blood are typically <500/mm 3 , they are of great importance ( 1 ). On the one hand, together with T lymphocytes, eosinophils participate in the acquired immunity against bacteria, viruses, and tumors ( 2 , 3 ).…”