Hypereosinophilic Syndrome Research Articles

FULMINANT EOSINOPHILIC MYOCARDITIS TREATED WITH STEROIDS AND INTRA–AORTIC BALLOON PUMP

Abstract Background Hypereosinophilic syndrome (HES) is a hematological disorders characterized by a chronic, unexplained hypereosinophilia (HE) with tissue damage. Cardiac involvement occurs in ∼20% of patients with HES and it carries a poor prognosis.Early detection and treatment of myocardial involvement improves prognosis. Immunosuppressive therapy represents the core treatment in the majority of patients with Eosinophilic Myocarditis. Case Summary 50–year–old man with history of intrinsic asthma and HE was admitted for cardiogenic shock B stage according SCAI classification (heart rate was 130 bpm, systolic blood pressure was 90 mmHg and lactate <2). EKG showed sinus tachycardia and diffuse ST segment depression. Echocardiography revealed severe left ventricular systolic dysfunction and mild pericardial effusion. Blood test showed leukocytosis (33x10^9/L) with HE (47%), mild hepato–renal damage, high TroponinT 3874 pg/mL and NT–proBNP 11060 ng/L. Coronary angiography was unremarkable. Pulmonary artery catheter was placed: IC 1,78 l/min/mq, CPO 0,63, WP 21, SVO2 60%, SVR 17 WU, RAP/WP 0.74. We reclassified patients as SCAI C with “mixed shock” due to inflammatory component and latent right ventricular dysfunction. Intra–aortic balloon pump (IABP) was placed and we performed endomyocardial biopsy (EMB). High dose of intra venous corticosteroids was started obtaining progressive improvement of hemodynamic parameters and reduction of inflammation parameters (Fig.1). EMB confirmed the diagnosis of myocarditis with initial transition into ‘’Loffler’s cardiomyopathy’’. Polymerase chain reaction (PCR) analysis did not detect cardiotropic viruses. After improvement of clinical status we performed cardiac MRI that revealed diffuse biventricular myocardial edema and the presence of subepicardial and mid–wall enhancement with non ischemic pattern,endocardial fibrosis and multiple left ventricular thrombi (Fig. 2). β–blockers and angiotensin–converting enzyme inhibitors were started and the patient was discharged at home with a complete myocardial recovery and immunosuppressive therapy based on corticosteroids and azathioprine. Discussion This case demonstrates the usefulness of myocardial biopsy in fulminant myocarditis. Treatment with corticosteroids resulted in rapid improvement. Early invasive monitoring allowed more precise hemodynamic characterization and mechanical circulatory support with IABP proved feasible and might have helped by unloading the left ventricle.

Not just for lymphoid cells: the role of the noncanonical NF-κB signaling pathway in early and late myelopoiesis with a focus on hypereosinophilic disorders.

The noncanonical NF-κB pathway is involved in lymphoid organ development, B-cell maturation, and cytokine production. However, new research has demonstrated that this pathway is also key for the orderly and sequential maturation of myeloid cells, including neutrophils and eosinophils. When this pathway is disrupted or constitutively activated, aberrations in hematopoietic stem and progenitor cell survival and proliferation, as well as subsequent granulopoiesis and eosinophilopoiesis, are affected. Disturbance of such a coordinated and delicate process can manifest in devastating clinical disease, including acute and chronic myeloid leukemias, preleukemic processes such as myelodysplastic syndrome, or hyperinflammatory conditions like hypereosinophilic syndrome. In this review, we discuss the molecular machinery within the noncanonical NF-κB pathway, crosstalk with the canonical NF-κB pathway, murine models of noncanonical signaling, and how aberrations in this pathway manifest in leukemic or hyperinflammatory disease with a focus on hypereosinophilic syndrome. Potential and promising drug therapies will also be discussed, emphasizing the noncanonical NF-κB pathway as a potential target for improved treatment for patients with leukemia or idiopathic hypereosinophilic syndrome. The hope is that review of such mechanisms and treatments may eventually result in findings that aid physicians in rapidly diagnosing and more accurately classifying patients with such complex and overlapping hematopoietic diseases.

Flow cytometric immunophenotypic differentiation patterns of bone marrow eosinophilopoiesis.

Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing identification of changes in patterns in many myeloid malignancies. Eosinophils play an important role in a wide variety of disorders, including some myeloid neoplasms. However, changes in flow cytometric immunophenotypic patterns during normal and abnormal bone marrow eosinophilopoiesis have not been well studied. Fresh bone marrow aspirates from 15 healthy donors, 19 patients with hypereosinophilic syndromes (HES), and 11 patients with systemic mastocytosis (SM) were analyzed for candidate markers that included EMR-1, Siglec-8, CCR3, CD9, CD11a, CD11b, CD11c, CD13, CD16, CD29, CD34, CD38, CD45, CD44, CD49d, CD49f, CD54, CD62L, CD69, CD117, CD125 (IL-5Rα), HLA-DR, using 10 parameter flow cytometry. Putative CD34-negative immature and mature normal eosinophil populations were first identified based on changes in expression of the above markers in healthy donors, then confirmed using fluorescence-based cell sorting and morphological evaluation of cytospin preparations. The normal immunophenotypic patterns were then compared to immunophenotypic patterns of eosinophilopoiesis in patients with HES and SM. The eosinophilic lineage was first verified using the human eosinophil-specific antibody EMR-1 in combination with anti-IL-5Rα antibody. Then, a combination of Siglec-8, CD9, CD11b, CCR3, CD49d, and CD49f antibodies was used to delineate normal eosinophilic maturational patterns. Early stages (eosinophilic promyelocytes/myelocytes) were identified as Siglec-8 dim/CD11b dim to moderate/CD9 dim/CCR3 dim/CD49d bright/CD49f dim, intermediate stages (eosinophilic myelocytes/metamyelocytes) as Siglec-8 moderate/CD11b moderate to bright/CD9 moderate/CCR3 moderate/CD49d moderate/CD49f moderate and mature bands/segmented eosinophils as Siglec-8 bright/CD11b bright/CD9 bright/CCR3 bright/CD49d dim/CD49f bright. Overall maturational patterns were also similar in patients with HES and SM; however, the expression levels of several surface markers were altered compared to normal eosinophils. A novel flow cytometric antibody panel was devised to detect alterations in immunophenotypic patterns of bone marrow eosinophil maturation and evaluated in normal, HES and SM samples. This approach will allow us to elucidate changes in immunophenotypic patterns of bone marrow eosinophilopoiesis in other hematological diseases.

Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review.

Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia. We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations. Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4). This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

Involvement of the JAK-STAT pathway in the molecular landscape of tyrosine kinase fusion-negative hypereosinophilic syndromes: A nationwide CEREO study.

We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion-negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HEUS used as controls; p < .001). Thirty-five patients (54%) had at least one mutation involving the JAK-STAT pathway, including STAT5B (n = 18, among which the hotspot N642H, n = 13), JAK1 (indels in exon 13, n = 5; V658F/L, n = 2), and JAK2 (V617F, n = 6; indels in exon 13, n = 2). Other previously undescribed somatic mutations were also found in JAK2, JAK1, STAT5B, and STAT5A, including three patients who shared the same STAT5A V707fs mutation and features consistent with primary polycythemia. Nearly all JAK-STAT mutations were preceded by (or associated with) myelodysplasia-related gene mutations, especially in RNA-splicing genes or chromatin modifiers. In multivariate analysis, neurologic involvement (hazard ratio [HR]4.95 [1.87-13.13]; p = .001), anemia (HR 5.50 [2.24-13.49]; p < .001), and the presence of a high-risk mutation (as per the molecular international prognosis scoring system: HR 6.87 [2.39-19.72]; p < .001) were independently associated with impaired overall survival. While corticosteroids were ineffective in all treated JAK-STAT-mutated patients, ruxolitinib showed positive hematological responses including in STAT5A-mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion-negative HE/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK-STAT mutations and eosinophilia as a new "gene mutated-entity" that could be differentiated from CEL, NOS, and idiopathic HES.

A Case of Eosinophilic Infiltration of the Right Heart: Diagnostic and Management Considerations

Loeffler first described “fibroplastic parietal endocarditis with blood eosinophilia” in 1936. This we now know refers to the most common cardiac manifestation of an uncommon condition, the so-called hypereosinophilic syndromes. This condition typically results in a restrictive cardiomyopathy affecting the left heart, but here, we present an unusual case of a 65-year-old woman with chronic hypereosinophilia of at least 2 years, who presented with right heart failure as a result of eosinophilic endomyocardial infiltration of her right ventricle. We explore the diagnostic pathway and look at the literature on management.

Лечение агрессивного системного мастоцитоза и тучноклеточного лейкоза. Обзор литературы и серия клинических наблюдений

Aim. To provide case reports on the course and treatment of aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL).&#x0D; Materials &amp; Methods. This paper reports the histories of adult patients with ASM (n = 4) and MCL (n = 2) treated with cytoreduction predominantly at the City Clinical Hospital No. 31 (Saint Petersburg). The patients were 36–61 years of age (median 50 years); there were 4 women and 2 men.&#x0D; Results. All patients showed stable response to cladribine (n = 3), imatinib (n = 2), and combined lenalidomide, elotuzumab, and dexamethasone treatment with subsequent allogeneic hematopoietic stem cell transplantation (n = 1). With a median follow-up of 124 months (range 55–186 months), 1 out of 2 MCL patients died due to the concomitant hypereosinophilic syndrome progression and secondary infectious complication.&#x0D; Conclusion. Cladribine therapy in 2 ASM patients and imatinib therapy in 2 MCL patients yielded stable long-term response with good quality of life being maintained. More comparative studies are required for efficacy assessment and optimum sequencing of chemotherapeutic drugs.

Clinical and Therapeutic Intervention of Hypereosinophilia in the Era of Molecular Diagnosis.

Hypereosinophilia (HE) presents with an elevated peripheral eosinophilic count of >1.5 × 109/L and is composed of a broad spectrum of secondary non-hematologic disorders and a minority of primary hematologic processes with heterogenous clinical presentations, ranging from mild symptoms to potentially lethal outcome secondary to end-organ damage. Following the introduction of advanced molecular diagnostics (genomic studies, RNA sequencing, and targeted gene mutation profile, etc.) in the last 1-2 decades, there have been deep insights into the etiology and molecular mechanisms involved in the development of HE. The classification of HE has been updated and refined following to the discovery of clinically novel markers and targets in the 2022 WHO classification and ICOG-EO 2021 Working Conference on Eosinophil Disorder and Syndromes. However, the diagnosis and management of HE is challenging given its heterogeneity and variable clinical outcome. It is critical to have a diagnostic algorithm for accurate subclassification of HE and hypereosinophilic syndrome (HES) (e.g., reactive, familial, idiopathic, myeloid/lymphoid neoplasm, organ restricted, or with unknown significance) and to follow established treatment guidelines for patients based on its clinical findings and risk stratification.

World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.

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. 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. 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. 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.

Eosinophilic Myocarditis: From Bench to Bedside.

Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis.

Biologic therapy in rare eosinophil-associated disorders: remaining questions and translational research opportunities.

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.

Eosinophil-associated diseases: the Allergist's and Clinical Immunologist's perspective.

Eosinophil-associated diseases (EADs) refer to heterogeneous conditions in which eosinophils are believed to play critical pathological roles. They encompass common respiratory conditions, such as asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), less common primary eosinophilic disorders of gastrointestinal tract, and rare conditions including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). A literature search was carried out in January 2024 in the MEDLINE and Scopus databases using the PubMed search engine (PubMed, National Library of Medicine, Bethesda, MD). We focused on blood eosinophilia and hypereosinophilia. A diagnostic workup is proposed. From allergist's point of view, we focused the review on 4 groups of eosinophilic disorders of specific interest. Our increased understanding of type 2 inflammation and biology has recently led to development of highly effective precision targeted therapies that are now approved for a growing number of eosinophilic disorders. Novel targeted biologics have a major impact on treatment strategies and have resulted in major advances in our understanding of the pathogenesis of these disorders. In the context of EADs, according to the heterogeneity of eosinophilic disorders a multidisciplinary approach should be adopted. Allergists and Clinical Immunologists play an important role as they have a clear understanding of the eosinophilic inflammation and the role of cytokines and are trained to recognize and characterize type 2 (T2) inflammation and its associated pathologies.

Idiopathic hypereosinophilic syndrome with gastrointestinal involvement

Idiopathic hypereosinophilic syndrome with gastrointestinal involvement

Cardiac Mechanics and Valvular and Vascular Abnormalities in Hypereosinophilic Syndrome.

Hypereosinophilic syndrome (HES) is considered to be a rare myeloproliferative disease that is characterized by persistent eosinophilia with associated multiple-organ damage. The heart is often involved in HES, representing a major cause of morbidity and mortality. HES is a heterogeneous group of disorders; the majority of the cases are idiopathic. Summarizing the findings regarding myocardial, valvular, and vascular abnormalities in a series of patients with HES, most studies found normal left ventricular (LV) volumes with reduced LV global longitudinal strain and LV apical rotation and twist in HES cases, accompanied by increased left atrial (LA) volumes and stroke volumes, reduced peak LA circumferential strain (representing systolic abnormalities), and mitral annular dilation and functional deterioration. Regarding the right heart, preserved right ventricular volumes and functional properties, increased right atrial volumes, mild RA functional abnormalities, and dilated tricuspid annular dimensions without functional impairment could be seen in these studies. Aortic and pulmonary valves showed no specific disease-related alterations. Vascular abnormalities included increased aortic stiffness without dilation of the aorta and pulmonary hypertension in some cases. These results suggest disease-specific but relatively mild myocardial, valvular, and vascular abnormalities in HES. The present review aimed to summarize the available clinical data about cardiac mechanics and valvular and vascular abnormalities in a series of patients with HES.

Development of a prediction model for hypereosinophilic syndrome using real-world data

Development of a prediction model for hypereosinophilic syndrome using real-world data

Single Center Off-Label Benralizumab use for Refractory Hypereosinophilic Syndrome Demonstrates Satisfactory Safety and Efficacy

Single Center Off-Label Benralizumab use for Refractory Hypereosinophilic Syndrome Demonstrates Satisfactory Safety and Efficacy

Lymphocytic variant of hypereosinophilic syndrome: Diagnostic challenge

T-cell phenotyping by flow cytometry and PCR analysis of TCR gene rearrangement patterns, are necessary to assess the diagnosis of Lymphocytic variant of Hypereosinophilic Syndrome (L-HES). The aim of this study was to evaluate the diagnostic contribution of flow cytometry using a single panel.

Hypereosinophilic syndrome: Case series and review of the literature

Abstract&#x0D; Hypereosinophilic Syndrome (HES) is caused by the uncontrolled proliferation of eosinophils generally associated with conditions such as allergic reactions or parasitic infections. This syndrome is characterized by excessive eosinophil production (&gt;1500/mm3) that persists for more than six months and cannot be explained by secondary causes. HES symptoms can affect different body organs, and usually, nonspecific symptoms include fever, malaise, fatigue, rash, shortness of breath, and myalgia.&#x0D; HES is a rare disease with multiorgan involvement, including the skin, joints, kidneys, vascular system, gastrointestinal tract, cardiac and pulmonary systems. The main feature of this disease is that overproduced eosinophils accumulate in organs and cause organ damage. Cardiac involvement plays a critical role in determining morbidity and mortality, and cardiac and large vessel thrombosis with severe clinical manifestations can also be observed.&#x0D; Treatment aims to reduce the absolute eosinophil count, improve symptoms, and prevent disease progression. Pharmacologic therapy aims to maintain targeted eosinophil levels below 1.5 x 10^9/L (1500 cells/mcL) to reduce the symptoms of eosinophilic disease and prevent organ damage. Furthermore, indications for emergency treatment should be rapidly assessed and initiated promptly in appropriate patients.&#x0D; This paper will discuss the diagnosis, clinical manifestations, treatment modalities, and management challenges of HES in detail through two rare case examples.

Hypereosinophilic Syndrome with COVID-19 Leading to Myocarditis and Stroke; A Case Report and Literature Review

Hypereosinophilic Syndrome with COVID-19 Leading to Myocarditis and Stroke; A Case Report and Literature Review

Hematological Neoplasms with Eosinophilia.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.