Epidemiology, clinical presentation, and outcomes of 620 patients with eosinophilia in the intensive care unit

Gaillet, Antoine; Bay, Pierre; Péju, Edwige; Ait‐Oufella, Hafid; Azoulay, Élie; Benchabane, Nacime; Cerf, Charles; Cohen, Yves; Prost, Nicolas de; Faguer, Stanislas; Géri, Guillaume; Grangé, Steven; Kahn, Jean‐Emmanuel; Kreitmann, Louis; Larcher, Romaric; Lefèvre, Guillaume; Mabrouki, Asma; Dessap, Armand Mekonsto; Panel, Kewin; Pène, Frédéric; Chambrun, Marc Pineton de; Quenot, Jean-Pierre; Tandjaoui-Lambiotte, Yacine; Timsit, Jean‐François; Vieillard‐Baron, Antoine; Dargent, Auguste; Herault, Antoine; Groh, Matthieu

doi:10.1007/s00134-022-06967-9

Cited by 4 publications

(11 citation statements)

References 51 publications

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“…6 Likewise, our group has previously shown that watershed strokes were present in up to 10% of patients with FIP1L1::PDGFRA-associated myeloid neoplasm with eosinophilia 29 and that the latter could be lifethreatening. 30 As all patients but one with JAK-STAT mutations had concomitant mutations commonly reported in MDS/CMML (and with higher VAF in most cases), the fact that high-risk mutations (as per the IPSS-M) also correlate with inferior OS in this study further substantiates the fact that JAK-STAT mutations do not occur de novo but rather in the setting of pre-existing clonal hematopoiesis. In line with previous studies, our findings also confirm that patients with STAT5B mutations tend to have specific phenotypes (e.g., CMML or MDS/MPN-SF3B1-T) according to the presence or not of comutations (e.g., ASXL1 or SF3B1, respectively).…”

Section: Predictors Of Death In the Experimental Groupsupporting

confidence: 75%

“…Interestingly, a hemoglobin level of <10 g/dL was already underscored as a poor prognostic factor in the study from the Mayo clinic group 6 . Likewise, our group has previously shown that watershed strokes were present in up to 10% of patients with FIP1L1::PDGFRA ‐associated myeloid neoplasm with eosinophilia 29 and that the latter could be life‐threatening 30 . As all patients but one with JAK‐STAT mutations had concomitant mutations commonly reported in MDS/CMML (and with higher VAF in most cases), the fact that high‐risk mutations (as per the IPSS‐M) also correlate with inferior OS in this study further substantiates the fact that JAK‐STAT mutations do not occur de novo but rather in the setting of pre‐existing clonal hematopoiesis.…”

Section: Discussionmentioning

confidence: 73%

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

Groh,

Fenwarth,

Labro

et al. 2024

American J Hematol

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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.

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Section: Predictors Of Death In the Experimental Groupsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 73%

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

Groh,

Fenwarth,

Labro

et al. 2024

American J Hematol

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“…Finally, the prognosis of idiopathic HES depends mainly on the severity of the initial complications, with cardiac, CNS and thrombotic symptoms being the most severe HES manifestations [ 37 – 41 ]. In other cases, the prognosis of idiopathic HES patients is most likely close to that of the general population, with corticosteroids showing remarkable efficacy in severe complications and the use of steroid-sparing treatments, including new biologic therapies, likely to revolutionize the management of non-clonal HES.…”

Section: General Informationmentioning

confidence: 99%

“…Likewise, the history of previous CBC can be instructive. The main drug classes that are routinely implicated in HE are non-steroidal anti-inflammatory drugs, antiepileptic drugs, antibiotics, sulfonamides and allopurinol [ 37 , 44 ]. More recently, dupilumab (an anti-IL4/IL13 biologic) and immune checkpoint inhibitors have also been shown to provide HE [ 45 , 46 ].…”

Section: Initial Assessmentmentioning

confidence: 99%

“…3 ). These mainly include cardiac manifestations ( e.g., eosinophilic myocarditis, intracavitary thrombosis with peripheral or cerebral embolic events, coronary artery spasm, acute heart failure), respiratory disorders (severe acute asthma or hypoxic lung disease), central nervous system manifestations (typically strokes of bilateral watershed distribution) and thrombotic (either arterial or venous) events [ 37 – 41 ]. Contrariwise, in the absence of overt clinical manifestations, very high eosinophil counts (e.g., > 10 × 10 9 /L) are not per se an indication for emergency initiation of treatment.…”

Section: Therapeutic Managementmentioning

confidence: 99%

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French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes

Groh

Rohmer

Etienne

et al. 2023

Orphanet J Rare Dis

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Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients’ association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges.

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Diagnosis and management of autoimmune diseases in the ICU

Dumas,

Arabi,

Bartz

et al. 2023

Intensive Care Med

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Epidemiology, clinical presentation, and outcomes of 620 patients with eosinophilia in the intensive care unit

Cited by 4 publications

References 51 publications

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

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

French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes

Diagnosis and management of autoimmune diseases in the ICU

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