Seminars in Hematology RSS feed: Current Issue. Seminars in Hematology is a topical journal that focuses on subjects of current importance in clinical hematology and related fields. The journal is devoted to making the present status of such topics and the results of new investigations readily available to the practicing physician. Seminars in Hematology is of special interest to hematologists, oncologists, internal medicine specialists, blood bankers and specialists in thrombosis and hemostasis. http://www.seminhematol.org/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Seminars in Hematology0037-1963492April 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.seminhematol.org/article/PIIS003719631200011X/abstract?rss=yesCover10.1053/S0037-1963(12)00011-XSeminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0OFCOFChttp://www.seminhematol.org/article/PIIS0037196312000121/abstract?rss=yesMasthead10.1053/S0037-1963(12)00012-1Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0IFCIFChttp://www.seminhematol.org/article/PIIS0037196312000054/abstract?rss=yesSince the first descriptions of “unexplained eosinophilia” in the early 1900s, the etiology and pathogenesis of eosinophilia in human disease has provoked controversy. This stems, in part, from the fact that the end results of eosinophilic inflammation in tissues are often similar regardless of the underlying cause. In 1975, Chusid et al published their landmark paper defining “the hypereosinophilic syndrome” (HES) on the basis of three criteria: (1) a persistent eosinophilia of 1,500/μL for 6 months, or death before 6 months associated with signs and symptoms of hypereosinophilic disease; (2) a lack of evidence for parasitic, allergic, or known causes of eosinophilia; and (3) presumptive signs of organ involvement. Although they recognized at the time that this broad case definition included patients with a variety of disorders, including chronic eosinophilic leukemia and eosinophilic collagen vascular diseases, it is only recently that the molecular and immunologic tools have become available to begin to dissect out the underlying etiologies of “idiopathic” HES.Eosinophilia: IntroductionAmy D. Klion10.1053/j.seminhematol.2012.01.004Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0111112http://www.seminhematol.org/article/PIIS0037196312000066/abstract?rss=yes Eosinophils are granulocytic innate immune cells whose presence is conspicuous in a variety of disease states, including eosinophilic hyperproliferative and infiltrative processes, as well as conditions associated with maladaptive Th2 inflammation. This review discusses the role of eosinophils in disease pathogenesis, including a consideration of relevant eosinophil biology. Eosinophilic disease patterns of tissue infiltration are also detailed, as are candidate mechanisms by which eosinophils cause fibrosis and hypercoagulability and the importance of eosinophils in allergic inflammation. Eosinophils are unique cells in their spectrum of associated disease, with the promise of future discoveries in delineating the manner in which they contribute to disease pathogenesis. Eosinophils and Disease PathogenesisPraveen Akuthota, Peter F. Weller10.1053/j.seminhematol.2012.01.005Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0113119http://www.seminhematol.org/article/PIIS0037196312000091/abstract?rss=yes The discovery of therapeutically relevant mutations involving platelet-derived growth factor receptors alpha and beta (PDGFRA and PDGFRB) changed the way we evaluate and treat patients with clonal eosinophilia. Despite our improved understanding of the pathobiology of clonal eosinophilia, more than 50% of patients are diagnosed with idiopathic disease, 10% to 20% with a clonal myeloid disorder, and the remainder with a lymphocytic variant. The World Health Organization classification of tumors recognized the importance of a semi-molecular classification of eosinophilc myeloid disorders and divided them into two major subgroups: (1) myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or fibroblast growth factor receptor 1 (FGFR1); and (2) chronic eosinophilic leukemia, not otherwise specified. A key challenge remains the identification of tyrosine kinase responsive molecular lesions in patients in whom the pathogenesis of clonal eosinophilia remains unclear. Eosinophilic Myeloid DisordersPierre Noel10.1053/j.seminhematol.2012.01.008Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0120127http://www.seminhematol.org/article/PIIS003719631200008X/abstract?rss=yes Mast cells and eosinophils often travel in the same biologic circles. In non-clonal states, such as allergic and inflammatory conditions, cell-to-cell contact and the pleiotropic actions of multiple cytokines and chemokines, derived from local tissues or mast cells themselves, foster the co-recruitment of these cells to the same geographic cellular niche. While eosinophils and mast cells serve critical roles as part of the host immune response and in maintenance of normal homeostasis, these cell types can undergo neoplastic transformation due to the development of clonal molecular abnormalities that arise in early hematopoietic progenitors. The dysregulated tyrosine kinases, D816V KIT and FIP1L1-PDGFRA, are the prototypic oncogenic lesions resulting in systemic mastocytosis (SM) and chronic eosinophilic leukemia, respectively. We review the pathobiology of these myeloproliferative neoplasms (MPNs) with a focus on the relationship between mast cells and eosinophils, and discuss murine models, which further elucidate how the phenotype of these diseases can be influenced by stem cell factor (SCF) and expression of the potent eosinophilopoietic cytokine, interleukin-5 (IL-5). Therapy of SM and FIP1L1-PDGFRA–positive disease and the prognostic relevance of increased peripheral blood and tissue mast cells in hematolymphoid malignancies will also be addressed. Mast Cells and Eosinophils in Mastocytosis, Chronic Eosinophilic Leukemia, and Non-clonal DisordersJason Gotlib, Cem Akin10.1053/j.seminhematol.2012.01.007Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0128137http://www.seminhematol.org/article/PIIS0037196312000042/abstract?rss=yes Hypereosinophilia, defined as peripheral blood eosinophil counts >1,500/μL, may complicate the course of various lymphoproliferative disorders. Among these, Hodgkin lymphoma (HL) and certain peripheral T-cell lymphomas (PTCLs) derived from CD4 cells, including Sezary syndrome (SS), adult T-cell leukemia/lymphoma (ATLL), and angioimmunoblastic T-cell lymphoma (AITL), are most commonly associated with increased reactive eosinophilopoiesis. Rarely, marked hypereosinophilia (HE) may occur in the setting of acute B-cell lymphoblastic leukemia, with a substantial impact on disease course. The mechanisms leading to blood and tissue eosinophilia in the setting of lymphoproliferative disorders, as well as the clinical complications and prognostic implications of hypereosinophilia, are discussed in this review. Lymphoproliferative Disorders Associated With HypereosinophiliaFlorence Roufosse, Soizic Garaud, Laurence de Leval10.1053/j.seminhematol.2012.01.003Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0138148http://www.seminhematol.org/article/PIIS0037196312000078/abstract?rss=yes High-grade eosinophilia can be a diagnostic dilemma, as the etiologies are extensive and varied. Hypereosinophilic syndromes (HES) are a group of heterogeneous disorders, many of which remain poorly defined. By definition, HES must be distinguished from other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, non-infectious causes must be considered, and include drug reactions, malignancies, and immunologic, inflammatory and allergic diseases. Evaluation and Differential Diagnosis of Marked, Persistent EosinophiliaRojelio Mejia, Thomas B. Nutman10.1053/j.seminhematol.2012.01.006Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0149159http://www.seminhematol.org/article/PIIS0037196312000030/abstract?rss=yes Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders that range from asymptomatic eosinophilia >1,500/mL to aggressive disease complicated by life-threatening end organ involvement, including endomyocardial fibrosis and thromboembolism. To complicate matters further, similar clinical manifestations can occur in the setting of marked eosinophilia due to helminth infection, drug hypersensitivity, and other causes. In the past, therapy was guided only by the exclusion of these secondary causes of eosinophilia and the severity of the clinical manifestations. More recently, the availability of novel targeted therapies and a better understanding of the etiologies of some subtypes of HES have necessitated a more structured approach. Therapeutic Approaches to Patients With Hypereosinophilic SyndromesHans-Uwe Simon, Amy Klion10.1053/j.seminhematol.2012.01.002Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0160170http://www.seminhematol.org/article/PIIS0037196312000108/abstract?rss=yes Eosinophilia is frequently detectable in certain myeloid neoplasms and various reactive conditions, but it may also occur in the absence of an apparent underlying disease, or, rarely, as a paraneoplastic feature with solid tumors. In myeloid neoplasms, eosinophils are considered to belong to the malignant clone in most cases, whereas in all other conditions, eosinophilia is a reactive process triggered by eosinopoietic cytokines. Excessive accumulation of eosinophils, also termed hypereosinophilia (HE), is typically seen in eosinophilic leukemias, but it may also occur in other neoplasms and reactive disorders. HE-related end organ damage may develop in patients with reactive HE but also in those with hematologic malignancies. During the past few years, our knowledge about HE and HE-related organ damage in hematologic and nonhematologic disorders has improved considerably. Moreover, proposals for the definition and classification of eosinophil disorders have been generated by various expert groups and by the World Health Organization (WHO). However, several questions related to eosinophils and HE remain open, and many aspects of the definition and classification of eosinophil disorders and related pathologies remain controversial. In the current article, these open issues are discussed with special reference to the 2008 WHO classification of myeloid neoplasms and other classifications proposed by immunologists and various expert panels, as well as definitions and criteria recently proposed in a multidisciplinary consensus proposal. Controversies and Open Questions in the Definitions and Classification of the Hypereosinophilic Syndromes and Eosinophilic LeukemiasPeter Valent, Hans-Peter Horny, Bruce S. Bochner, Torsten Haferlach, Andreas Reiter10.1053/j.seminhematol.2012.01.009Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0171181http://www.seminhematol.org/article/PIIS0037196312000029/abstract?rss=yes Treatment of the hypereosinophilic syndrome (HES) has advanced rapidly and prevention of end organ damage previously associated with the disorders is now possible in most patients who have had a timely diagnosis. Tried and true medications such as prednisone, hydroxyurea, and interferon-alpha (IFN-aα) continue to play a valuable role in treating HES and their cost is modest. Newer medications included pegylated forms of IFN-aα and IFN-α2b, first- and second-generation tyrosine kinase inhibitors (imatinib mesylate, nilotinib), and monoclonal antibodies to interleukin (IL)-5 and CD52. The combination of better understanding of HES and better medications now provide the clinician with an improved ability to control unregulated proliferation of eosinophils. Treatment of Hypereosinophilic Syndromes—The First 100 YearsJ.H. Butterfield, C.R. Weiler10.1053/j.seminhematol.2012.01.001Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0182191http://www.seminhematol.org/article/PIIS0037196312000157/abstract?rss=yesFuture Issues and Recent Issues10.1053/S0037-1963(12)00015-7Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0192192http://www.seminhematol.org/article/PIIS0037196312000133/abstract?rss=yesTable of Contents10.1053/S0037-1963(12)00013-3Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0FrontmatterA1A1http://www.seminhematol.org/article/PIIS0037196312000145/abstract?rss=yesPrevious Issues10.1053/S0037-1963(12)00014-5Seminars in Hematology 49, 2 (2012)2012-04-01Seminars in Hematology2012-04-01492S0037-1963(11)X0007-0FrontmatterA2A2