Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy

Ogbogu, Princess U.; Bochner, Bruce S.; Butterfield, Joseph H.; Gleich, Gerald J.; Huss‐Marp, Johannes; Kahn, Jean‐Emmanuel; Leiferman, Kristin M.; Nutman, Thomas B.; Pfab, Florian; Ring, Johannes; Rothenberg, Marc E.; Roufosse, Florence; Sajous, Marie-Helene; Sheikh, Javed; Simon, Dagmar; Simon, Hans‐Uwe; Stein, Miguel; Wardlaw, Andrew J.; Weller, Peter F.; Klion, Amy D.

doi:10.1016/j.jaci.2009.09.022

Cited by 543 publications

(606 citation statements)

References 18 publications

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“…In contrast, idiopathic hypereosinophilic syndrome patients with no identifiable mutations presented with hypereosinophilia at a much younger age than chronic eosinophilic leukemia, not otherwise specified, and had more frequent symptoms associated with eosinophil activation, such as dermatological, pulmonary, gastrointestinal, and rheumatologic manifestations, as has been reported by others. 4,28 Compared with the contrasting clinical features of idiopathic hypereosinophilic syndrome/next-generation sequencing-negative vs chronic eosinophilic leukemia, not otherwise specified, the clinical manifestations of idiopathic hypereosinophilic syndrome/next-generation sequencing-positive as a group were more heterogeneous, but showed some similarities to chronic eosinophilic leukemia, not otherwise specified. The disease-specific survival of chronic eosinophilic leukemia, not otherwise specified patients was significantly shorter than that of idiopathic hypereosinophilic syndrome/next-generation sequencing-negative patients (P o 0.001), but was not statistically different from idiopathic hypereosinophilic syndrome/next-generation sequencingpositive patients (P = 0.117).…”

Section: Discussionmentioning

confidence: 99%

“…The latter nine cases showed excellent test concordance between the two types of archived samples. The 45-gene panel (sequencing 490% gene coding regions) was conducted on 44 patient samples, 28-gene panel (sequencing entire coding regions) on 9, and 50-gene panel on 4. Among the nine samples tested by the 28-gene panel, CSF3R mutation was additionally tested by Sanger sequencing in two patients.…”

Section: Patients and Mutational Studiesmentioning

confidence: 99%

“…As a result, idiopathic hypereosinophilic syndrome has become a heterogeneous entity with variable clinical behavior in affected patients. 3,4 In recent years, next-generation sequencing has helped to identify mutations in a large proportion of cases of myeloid neoplasms. In myeloproliferative neoplasms, discoveries include CALR mutations in JAK2 V617-negative classic myeloproliferative neoplasms, 5,6 as well as a number of recurrent mutations that correlate with the clinical features, prognosis, and treatment responses.…”

Section: Introductionmentioning

confidence: 99%

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Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified

et al. 2016

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The distinction between chronic eosinophilic leukemia, not otherwise specified and idiopathic hypereosinophilic syndrome largely relies on clonality assessment. Prior to the advent of next-generation sequencing, clonality was usually determined by cytogenetic analysis. We applied targeted next-generation sequencing panels designed for myeloid neoplasms to bone marrow specimens from a cohort of idiopathic hypereosinophilic syndrome patients (n = 51), and assessed the significance of mutations in conjunction with clinicopathological features. The findings were further compared with those of 17 chronic eosinophilic leukemia, not otherwise specified patients defined by their abnormal cytogenetics and/or increased blasts. Mutations were detected in 14/51 idiopathic hypereosinophilic syndrome patients (idiopathic hypereosinophilic syndrome/next-generation sequencing-positive) (28%), involving single gene in 7 and ≥ 2 in 7 patients. The more frequently mutated genes included ASXL1 (43%), TET2 (36%), EZH2 (29%), SETBP1 (22%), CBL (14%), and NOTCH1 (14%). Idiopathic hypereosinophilic syndrome/next-generation sequencing-positive patients showed a number of clinical features and bone marrow findings resembling chronic eosinophilic leukemia, not otherwise specified. Chronic eosinophilic leukemia, not otherwise specified patients showed a disease-specific survival of 14.4 months, markedly inferior to idiopathic hypereosinophilic syndrome/next-generation sequencing-negative (P o0.001), but not significantly different from idiopathic hypereosinophilic syndrome/next-generation sequencing-positive (P = 0.117). These data suggest that targeted next-generation sequencing helps to establish clonality in a subset of patients with hypereosinophilia that would otherwise be classified as idiopathic hypereosinophilic syndrome. In conjunction with other diagnostic features, mutation data can be used to establish a diagnosis of chronic eosinophilic leukemia, not otherwise specified in patients presenting with hypereosinophilia.

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Section: Discussionmentioning

confidence: 99%

Section: Patients and Mutational Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified

et al. 2016

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“…The relative frequencies of these variants in the general population are difficult to ascertain due in large part to the lack of universally accepted definitions of HES and referral bias (ie, a hematologist is more likely to see M-HES). Nevertheless, data from a multicenter retrospective study 16 and from our cohort of 307 consecutive patients referred for unexplained HE ( Figure 2) suggest that M-HES (including PDGFRA-associated MPN) and L-HES each account for 10% to 20% of patients with HES after treatable secondary causes are excluded.…”

Section: Clinical He/hes Variantsmentioning

confidence: 93%

How I treat hypereosinophilic syndromes

Klion

2015

Blood

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Hypereosinophilic syndromes (HESs) are a group of rare disorders characterized by peripheral blood eosinophilia of 1.5 × 109/L or higher and evidence of end organ manifestations attributable to the eosinophilia and not otherwise explained in the clinical setting. HESs are pleomorphic in clinical presentation and can be idiopathic or associated with a variety of underlying conditions, including allergic, rheumatologic, infectious, and neoplastic disorders. Moreover, the etiology of the eosinophilia in HESs can be primary (myeloid), secondary (lymphocyte-driven), or unknown. Although corticosteroids remain the first-line therapy for most forms of HESs, the availability of an increasing number of novel therapeutic agents, including tyrosine kinase inhibitors and monoclonal antibodies, has necessarily altered the approach to treatment of HESs. This review presents an updated treatment-based approach to the classification of patients with presumed HES and discusses the roles of conventional and novel agents in the management of these patients.

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“…Approximately one third of patients, however, will not respond to steroids. Hydroxyurea and interferon alpha are currently second-line drugs of choice and can be complemented by attempts of high dose imatinib, monoclonal antibodies against IL-5 (mepolizumab) or CD52 (alemtuzumab), or hematopoietic stem cell transplantation [2].…”

mentioning

confidence: 99%