Eosinophils are specialized marrow-derived myeloid cells that play an important role in regulating the innate and adaptive arms of the immune system, in addition to tissue repair and remodeling. Eosinophil functions are mediated by their granular contents that include various proteins, enzymes, and inflammatory mediators. Under pathologic conditions, eosinophils can accumulate in any tissue, releasing their mediators and recruiting other cells, resulting in inflammation, thrombosis, fibrosis, and tissue damage. Eosinophilia is most commonly reactive (secondary) to other disorders such as infections, allergies, medications, autoimmune diseases, and malignancies. The categorization of primary (clonal) eosinophilias was revised in the 2008 World Health Organization classification of myeloid neoplasms and further modified in 2016, after the discovery of molecularly-defined subtypes, including “myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2” in addition to “chronic eosinophilic leukemia, not otherwise specified.” A diagnosis of idiopathic hypereosinophilia requires the exclusion of all primary and secondary causes as well as lymphocyte-variant hypereosinophilia, which is characterized by expansion of immunophenotypically-aberrant T cells that elaborate eosinophilopoietic cytokines. Several advances in the diagnosis and treatment of primary eosinophilic disorders have been achieved and are discussed in this chapter.
Acronyms and Abbreviations
AEC, absolute eosinophil count; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CBF, core binding factor; CCyR, complete cytogenetic response; CEL, NOS, chronic eosinophilic leukemia, not otherwise specified; CHIP, clonal hematopoiesis of indeterminate potential; CHR, complete hematological response; CML, chronic myeloid leukemia; CMR, complete molecular response; CMML, chronic myelomonocytic leukemia; CT, computed tomography; ECP, eosinophil cationic protein; EGID, eosinophilic gastrointestinal disease; EPX, eosinophil peroxidase; FGFR, fibroblast growth factor receptor; FISH, fluorescence in situ hybridization; GM-CSF, granulocyte monocyte-colony stimulating factor; GMP, granulocyte macrophage progenitor; HE, hypereosinophilia; HES, hypereosinophilic syndrome; HIV, human immunodeficiency virus; HSCT, hematopoietic stem cell transplantation; hyper-CVAD (hyperfractionated therapy with cyclophosphamide, vincristine, doxorubicin hydrochloride [Adriamycin], and dexamethasone); IC50, half maximal inhibitory concentration; Ig, immunoglobulin; IL-5Rα, interleukin-5 receptor α; MBP, major basic protein; MCP, monocyte chemoattractant protein; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; NGS, next generation sequencing; NT-BNP, N-terminal pro B-type natriuretic peptide; PAF, platelet activating factor; PCR, polymerase chain reaction; PDGFR, platelet derived growth factor receptor; PET, positron emission tomography; RT, reverse transcriptase; SEER, Surveillance, Epidemiology and End Results; SM, systemic mastocytosis; TARC, thymus and activation regulated chemokine; WHO, World Health Organization
EOSINOPHILS AND THEIR BIOLOGY
Eosinophils are bilobed granulocytes derived from myeloid stem cells. They were initially characterized in 1879 by Paul Ehrlich, who pioneered the use of aniline dyes to stain cells within various tissues. He referred to cells with abundant cytoplasmic granules that show intense avidity to the synthetic acid red dye “Eosin” as eosinophils. “Eosin” is derived from “Eos,” the rosy-fingered Titan goddess of the dawn.1 In addition to their minor presence in the marrow and blood, mature eosinophils are normally present in the gastrointestinal (GI) tract (except the esophagus), lymphoid tissues (eg, ...