Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab

Rothenberg, Marc E.; Klion, Amy D.; Roufosse, Florence; Kahn, Jean‐Emmanuel; Weller, Peter F.; Simon, Hans‐Uwe; Schwartz, Lawrence B.; Rosenwasser, Lanny J.; Ring, Johannes; Griffin, Elaine F.; Haig, Ann; Frewer, Paul; Parkin, Jacqueline; Gleich, Gerald J.

doi:10.1056/nejmoa070812

Cited by 525 publications

(361 citation statements)

References 27 publications

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“…The identification of an IL-5/immunoglobulin complex after anti-IL-5 therapy defines the importance of further elucidating the structure and significance of this complex in patients. Given that mepolizumab has recently been demonstrated to offer steroid-sparing effects in patients with HES 21 and is promising for the treatment of eosinophilic disorders, 20 this report provides timely novel translational information. Horizontal bars represent mean (SD) values (n = 12).…”

Section: Discussionmentioning

confidence: 97%

“…[17][18][19][20] The first randomized, double-blind, placebo-controlled trial of patients with HES was recently conducted and aimed at demonstrating the ability of anti-IL-5 to decrease prednisone dependence in HES not associated with the constitutively activated tyrosine kinase FIP1L1-platelet-derived growth factor receptor α (FIP1L1-PDGFRA). 21 Impressively, this international trial revealed a striking ability of anti-IL-5 to decrease prednisone doses, decrease blood eosinophilia, and maintain clinical stability compared with placebo. Surprisingly, an indepth evaluation of the hematologic and immunologic effects of anti-IL-5 in human subjects has not been conducted (even in asthmatic individuals).…”

Section: Introductionmentioning

confidence: 96%

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Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels

Stein

Villanueva

Buckmeier

et al. 2008

Journal of Allergy and Clinical Immunology

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115

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 96%

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels

Stein

Villanueva

Buckmeier

et al. 2008

Journal of Allergy and Clinical Immunology

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130

115

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“…11,12 Exclusion of FIP1L1-PDGFRA is also important as some patients may benefit from alternative therapies such as mepolizumab. 13 Unambiguous detection of FIP1L1-PDGFRA, however, is complicated by several factors. Fluorescence in situ hybridization (FISH) to detect heterozygous deletion of CHIC2, a surrogate marker for FIP1L1-PDGFRA, can be difficult because of the inherent background fluorescence of eosinophils 9 and the variability in the proportion of cells involved in the malignant clone, 14,15 which is often low and may overlap with the intrinsic background false-positive rate of this technique.…”

Section: Introductionmentioning

confidence: 99%

Detection and molecular monitoring of FIP1L1-PDGFRA-positive disease by analysis of patient-specific genomic DNA fusion junctions

et al. 2008

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To evaluate current detection methods for FIP1L1-PDGFRA in hypereosinophilic syndrome (HES), we developed a means to rapidly amplify genomic break points. We screened 202 cases and detected genomic junctions in all samples previously identified as RT-PCR positive (n ¼ 43). Genomic fusions were amplified by single step PCR in all cases whereas only 22 (51%) were single step RT-PCR positive. Importantly, FIP1L1-PDGFRA was detected in two cases that initially tested negative by RT-PCR or fluorescence in situ hybridization. Absolute quantitation of the fusion by real-time PCR from genomic DNA (gDNA) using patient-specific primer/probe combinations at presentation (n ¼ 13) revealed a 40-fold variation between patients (range, 0.027-1.1 FIP1L1-PDGFRA copies/haploid genome). In follow up samples, quantitative analysis of gDNA gave 1-2 log greater sensitivity than RQ-PCR of cDNA. Minimal residual disease assessment using gDNA showed that 11 of 13 patients achieved complete molecular response to imatinib within a median of 9 months (range, 3-17) of starting treatment, with a sensitivity of detection of up to 1 in 10 5 . One case relapsed with an acquired D842V mutation. We conclude that detection of FIP1L1-PDGFRA from gDNA is a useful adjunct to standard diagnostic procedures and enables more sensitive follow up of positive cases after treatment.

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“…Other drugs include hydoxyurea, or Anti-IL-5 [20][21][22], either adding to steroids or as steroid sparing.…”

Section: Discussionmentioning

confidence: 99%

Idiopathic Hypereosinophilic Syndrome Presenting as IgA Nephropathy with Nephrotic Range Proteinuria

Shah¹,

Koul²,

Shah³

et al. 2013

OJNeph

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Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by increased eosinophil count (eosinophilia) along with organ dysfunction secondary to organ infiltration of eosinophils and release of inflammatory markers [1][2][3][4], with no obvious cause for eosinophilia. The onset of symptoms is insidious in most of the cases and eosinophilia is detected incidentally. However, in others, the initial manifestations are severe and life-threatening due to the rapid evolution of cardiac or neurologic complications [5]. Renal involvement is rarely reported [6] in IHES. Herein we reported a case of IHES with predominant renal involvement as nephrotic syndrome with focal necrotizing IgA nephropathy.Keywords: Idiopathic Hypereosinophilic Syndrome; Eosinophilia; Renal Involvement; Nephrotic Syndrome Case ReportA 50-year old male presented with a 3-week history of a non-productive cough, associated with intermittent low grade fever, periorbital puffiness and lower extremity edema. Patient denied any history of breathlessness, chest-pain, hemoptysis, orthopnea, paroxysmal nocturnal dyspnea, drop in urine output, skin rash or arthritis. His past history was insignificant and he denied any history of drug intake.Hisexamination revealed mild pallor, with periorbitalpuffiness, lower extremity pitting edema and mild splenomegaly. He had hemoglobin of 11 g/dL with a total leucocyte count of 9.2 × 10 9 /cumm and an ESR of 23 mmhr. His differential count included 46% polymorphs 11% lymphocytes and 41% eosinophils with AEC count of 3800 which repeatedly was high and ranged from 3800 to 5500. A peripheral blood film showed features of normochromic normocytic anaemia with no abnormal cells. His serum creatinine was 1.7 mg/dL with a creatinine clearance of 44 ml/min. Liver functions showed hypoporoteinemia with hypoalbuminemia. He had an active urinary sedimentand urine which showed presence of eosinophils on wright's staining. 24 hours urinary protein was 5.04 g/24hours which was reproduced twice. Repeated stool examination for the presence of ova/parasite was negative.Radiograph of the chest was normal. High resolution computerized tomography of the chest did not reveal any abnormality. His electrocardiograph and echocardiography were normal. Ultrasonography of abdomen was normal as well.Patient was investigated further to look for eosinophilic infiltration of other organ systems in view of persistant hypereosinophilia.Patient was subjected to bronchoscopy to obtain bronchoalveolar lavage for eosinophils which revealed 62% eosinophils. Bone marrow aspiration and biopsy revealed 56% eosinophils with no dysplasia and blasts. p-ANCA andc-ANCA were within normal limits. Serum tryptase levels were within normal limits.Patient was subjected to percutaneous renal biopsy to look for the etiology of nephrotic range proteinuria. Renal biopsy revealed, marked interstitial edema and patchy inflammation including aggregates of eosinophils admixed with mononuclear cells and occasional neutrophils. An eosinophilic infiltrate wa...

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Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab

Cited by 525 publications

References 27 publications

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels

Detection and molecular monitoring of FIP1L1-PDGFRA-positive disease by analysis of patient-specific genomic DNA fusion junctions

Idiopathic Hypereosinophilic Syndrome Presenting as IgA Nephropathy with Nephrotic Range Proteinuria

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