Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis and Novel Approaches to the Treatment of Hypereosinophilic Syndromes

  • Myeloproliferative Neoplasms (B Stein, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Hypereosinophilic syndrome (HES) is characterized by persistent hypereosinophilia associated with end-organ damage. As our understanding of the pathogenesis of various forms of HES broadens, so does our ability to tailor steroid-sparing therapies for each subtype. The purpose of this review is to summarize recent literature related to the etiology, diagnosis, and management of HES.

Recent Findings

Mutations involved in subsets of HES can guide the choice of tyrosine kinase inhibitors beyond just imatinib. Several biologics that target interleukin-5 or its receptor have shown beneficial and selective eosinophil-reducing effects in clinical trials for asthma and other disorders including HES. Early clinical data with emerging therapies such as dexpramipexole and anti-Siglec-8 antibody show promise, but need to be confirmed in randomized trials.

Summary

Several new biologics and tyrosine kinase inhibitors have been shown to lower eosinophil numbers, but more randomized trials are needed to confirm efficacy in HES.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

AEC:

Absolute eosinophil count

ASXL1:

Putative polycomb group protein ASXL1

CBL:

Cbl ubiquitin-protein ligase

CD:

Cluster of differentiation

EGID:

Eosinophilic gastrointestinal disease

EGPA:

Eosinophilic granulomatosis with polyangiitis

EMR1:

EGF-like module containing mucin-like hormone receptor

EoE:

Eosinophilic esophagitis

EZH2:

Enhancer of zeste homolog 2

GC:

Glucocorticoid

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HE:

Hypereosinophilia

HES:

Hypereosinophilic syndrome

IL:

Interleukin

JAK:

Janus kinase

NOTCH1:

Notch homolog 1, translocation-associated

STAT:

Signal transducer and activator of transcription

SETBP1:

SET-binding protein 1

sq:

Subcutaneous

TET2:

Tet methylcytosine dioxygenase 2

TSLP:

Thymic stromal lymphopoietin

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Bochner B. The eosinophil: for better or worse, in sickness and in health. Ann Allergy Asthma Immunol. 2018; (in press).

  2. Diny NL, Rose NR, Cihakova D. Eosinophils in autoimmune diseases. Front Immunol. 2017;8:484.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Valent P, Gleich GJ, Reiter A, Roufosse F, Weller PF, Hellmann A, et al. Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field. Expert Rev Hematol. 2012;5(2):157–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Walker S, Wang C, Walradt T, Hong BS, Tanner JR, Levinsohn JL, et al. Identification of a gain-of-function STAT3 mutation (p.Y640F) in lymphocytic variant hypereosinophilic syndrome. Blood. 2016;127(7):948–51.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lin AY, Nutman TB, Kaslow D, Mulvihill JJ, Fontaine L, White BJ, et al. Familial eosinophilia: clinical and laboratory results on a U.S. kindred. Am J Med Genet. 1998;76(3):229–37.

    Article  PubMed  CAS  Google Scholar 

  6. • Prakash Babu S, Chen YK, Bonne-Annee S, Yang J, Maric I, Myers TG, et al. Dysregulation of interleukin 5 expression in familial eosinophilia. Allergy. 2017;72(9):1338–45. This study showed that IL-5 and IL-5R dysregulation are involved in the pathogenesis of familial eosinophilia in one family cohort.

    Article  PubMed  CAS  Google Scholar 

  7. Rioux JD, Stone VA, Daly MJ, Cargill M, Green T, Nguyen H, et al. Familial eosinophilia maps to the cytokine gene cluster on human chromosomal region 5q31-q33. Am J Hum Genet. 1998;63(4):1086–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Del Bel KL, Ragotte RJ, Saferali A, Lee S, Vercauteren SM, Mostafavi SA, et al. JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome. J Allergy Clin Immunol. 2017;139(6):2016–20.

    Article  PubMed  CAS  Google Scholar 

  9. Wang SA, Hasserjian RP, Tam W, Tsai AG, Geyer JT, George TI, et al. Bone marrow morphology is a strong discriminator between chronic eosinophilic leukemia, not otherwise specified and reactive idiopathic hypereosinophilic syndrome. Haematologica. 2017;102(8):1352–60.

    Article  PubMed  PubMed Central  Google Scholar 

  10. • Wang SA, Tam W, Tsai AG, Arber DA, Hasserjian RP, Geyer JT, et al. Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified. Mod Pathol. 2016;29(8):854–64. This study showed that a significant proportion of patients diagnosed with “idiopathic” HES in fact have mutations in various housekeeping and signaling genes that are known to be associated with cancers.

    Article  PubMed  CAS  Google Scholar 

  11. Pardanani A, Lasho T, Wassie E, Finke C, Zblewski D, Hanson CA, et al. Predictors of survival in WHO-defined hypereosinophilic syndrome and idiopathic hypereosinophilia and the role of next-generation sequencing. Leukemia. 2016;30(9):1924–6.

    Article  PubMed  CAS  Google Scholar 

  12. Harfi I, Schandene L, Dremier S, Roufosse F. Eosinophils affect functions of in vitro-activated human CD3-CD4+ T cells. J Transl Med. 2013;11:112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Jin JJ, Butterfield JH, Weiler CR. Hematologic malignancies identified in patients with hypereosinophilia and hypereosinophilic syndromes. J Allergy Clin Immunol Pract. 2015;3(6):920–5.

    Article  PubMed  Google Scholar 

  14. Andersen CL, Siersma VD, Hasselbalch HC, Lindegaard H, Vestergaard H, Felding P, et al. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death. Am J Hematol. 2013;88(10):843–7.

    Article  PubMed  CAS  Google Scholar 

  15. Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009;124(6):1319–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Klion AD. Eosinophilia: a pragmatic approach to diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2015;2015:92–7.

    PubMed  Google Scholar 

  17. Katre RS, Sunnapwar A, Restrepo CS, Katabathina VS, Mumbower A, Baxi A, et al. Cardiopulmonary and gastrointestinal manifestations of eosinophil- associated diseases and idiopathic hypereosinophilic syndromes: multimodality imaging approach. Radiographics. 2016;36(2):433–51.

    Article  PubMed  Google Scholar 

  18. Butterfield JH, Kane GC, Weiler CR. Hypereosinophilic syndrome: endomyocardial biopsy versus echocardiography to diagnose cardiac involvement. Postgrad Med. 2017;129(5):517–23.

    Article  PubMed  Google Scholar 

  19. Klion AD. How I treat hypereosinophilic syndromes. Blood. 2015;126(9):1069–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. • Khoury P, Abiodun AO, Holland-Thomas N, Fay MP, Klion AD. Hypereosinophilic syndrome subtype predicts responsiveness to glucocorticoids. J Allergy Clin Immunol Pract. 2018;6(1):190–5. This study demonstrated that the myeloid and lymphocytic variants of HES are the least-responsive to treatment with glucocorticoids.

    Article  PubMed  Google Scholar 

  21. Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008;358(12):1215–28.

    Article  PubMed  CAS  Google Scholar 

  22. Roufosse FE, Kahn JE, Gleich GJ, Schwartz LB, Singh AD, Rosenwasser LJ, et al. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol. 2013;131(2):461–7.

    Article  PubMed  CAS  Google Scholar 

  23. Roufosse F, de Lavareille A, Schandene L, Cogan E, Georgelas A, Wagner L, et al. Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome. J Allergy Clin Immunol. 2010;126(4):828–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Schwarz C, Muller T, Lau S, Parasher K, Staab D, Wahn U. Mepolizumab—a novel option for the treatment of hypereosinophilic syndrome in childhood. Pediatr Allergy Immunol. 2018;29(1):28–33.

    Article  PubMed  Google Scholar 

  25. Guo C, Bochner BS. Mepolizumab as a successful steroid-sparing agent in two patients with idiopathic hypereosinophilic syndrome (iHES). J Allergy Clin Immunol. 2018;141(2):AB27.

    Article  Google Scholar 

  26. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129(2):456–63. 63

    Article  PubMed  CAS  Google Scholar 

  27. Murphy K, Jacobs J, Bjermer L, Fahrenholz JM, Shalit Y, Garin M, et al. Long-term safety and effficacy of reslizumab in patients with eosinophilic asthma. J Allergy Clin Immunol Pract. 2017;5(6):1572–81.

    Article  PubMed  Google Scholar 

  28. Klion AD, Law MA, Noel P, Kim YJ, Haverty TP, Nutman TB. Safety and efficacy of the monoclonal anti-interleukin-5 antibody SCH55700 in the treatment of patients with hypereosinophilic syndrome. Blood. 2004;103(8):2939–41.

    Article  PubMed  CAS  Google Scholar 

  29. Teva announces top-line results from phase III studies of subcutaneously administered reslizumab in patients with severe eosinophilic asthma. http://www.tevapharm.com/news/teva_announces_top_line_results_from_phase_iii_studies_of_subcutaneously_administered_reslizumab_in_patients_with_severe_eosinophilic_asthma_01_18.aspx.

  30. Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344–53.

    Article  PubMed  CAS  Google Scholar 

  31. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115–27.

    Article  PubMed  CAS  Google Scholar 

  32. FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–41.

    Article  PubMed  CAS  Google Scholar 

  33. • Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448–58. This is the most recently published phase 3 trial for benralizumab, confirming findings from the previous trials demonstrating benralizumab’s excellent eosinophil-depleting effects in severe eosinophilic asthma.

    Article  PubMed  CAS  Google Scholar 

  34. Kuang FL, Alao H, Kumar S, Powers A, Quezado M, Wang Z, et al. Benralizumab (anti-IL5Rα) depletes gut tissue eosinophilia and improves symptoms in hypereosinophilic syndrome with gastrointestinal involvement. J Allergy Clin Immunol. 2018;141((2):AB196.

    Article  Google Scholar 

  35. Massanari M, Holgate ST, Busse WW, Jimenez P, Kianifard F, Zeldin R. Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir Med. 2010;104(2):188–96.

    Article  PubMed  CAS  Google Scholar 

  36. Busse W, Spector S, Rosen K, Wang Y, Alpan O. High eosinophil count: a potential biomarker for assessing successful omalizumab treatment effects. J Allergy Clin Immunol. 2013;132(2):485–6.

    Article  PubMed  Google Scholar 

  37. Hanania NA, Wenzel S, Rosen K, Hsieh HJ, Mosesova S, Choy DF, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013;187(8):804–11.

    Article  PubMed  CAS  Google Scholar 

  38. Foroughi S, Foster B, Kim N, Bernardino LB, Scott LM, Hamilton RG, et al. Anti-IgE treatment of eosinophil-associated gastrointestinal disorders. J Allergy Clin Immunol. 2007;120(3):594–601.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Loizou D, Enav B, Komlodi-Pasztor E, Hider P, Kim-Chang J, Noonan L, et al. A pilot study of omalizumab in eosinophilic esophagitis. PLoS One. 2015;10(3):e0113483.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Clayton F, Fang JC, Gleich GJ, Lucendo AJ, Olalla JM, Vinson LA, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology. 2014;147(3):602–9.

    Article  PubMed  CAS  Google Scholar 

  41. Weinstein SF, Katial R, Jayawardena S, Pirozzi G, Staudinger H, Eckert L, et al. Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma. J Allergy Clin Immunol. 2018 (in press).

  42. Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388(10039):31–44.

    Article  PubMed  CAS  Google Scholar 

  43. Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, et al. Dupilumab efficacy and safety in adult patients with active eosinophilic esophagitis: a randomized double-blind placebo-controlled phase 2 trial. United Eur Gastro J. 2017;5(Suppl 1).

  44. Pitini V, Teti D, Arrigo C, Righi M. Alemtuzumab therapy for refractory idiopathic hypereosinophilic syndrome with abnormal T cells: a case report. Br J Haematol. 2004;127(5):477.

    Article  PubMed  Google Scholar 

  45. Wagner LA, Speckart S, Cutter B, Gleich GJ. Treatment of FIP1L1/PDGFRA-negative hypereosinophilic syndrome with alemtuzumab, an anti-CD52 antibody. J Allergy Clin Immunol. 2009;123(6):1407–8.

    Article  PubMed  Google Scholar 

  46. Verstovsek S, Tefferi A, Kantarjian H, Manshouri T, Luthra R, Pardanani A, et al. Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic leukemia. Clin Cancer Res. 2009;15(1):368–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377(10):936–46.

    Article  PubMed  CAS  Google Scholar 

  48. Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. Treatment of hypereosinophilic syndrome with imatinib mesylate. Lancet. 2002;359(9317):1577–8.

    Article  PubMed  CAS  Google Scholar 

  49. Ault P, Cortes J, Koller C, Kaled ES, Kantarjian H. Response of idiopathic hypereosinophilic syndrome to treatment with imatinib mesylate. Leuk Res. 2002;26(9):881–4.

    Article  PubMed  CAS  Google Scholar 

  50. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348(13):1201–14.

    Article  PubMed  CAS  Google Scholar 

  51. • Gotlib J. Tyrosine kinase inhibitors in the treatment of eosinophilic neoplasms and systemic mastocytosis. Hematol Oncol Clin North Am. 2017;31(4):643–61. An excellent and thorough review of the field.

    Article  PubMed  Google Scholar 

  52. Helbig G. Imatinib for the treatment of hypereosinophilic syndromes. Expert Rev Clin Immunol. 2018;14(2):163–70.

    Article  PubMed  CAS  Google Scholar 

  53. Jovanovic JV, Score J, Waghorn K, Cilloni D, Gottardi E, Metzgeroth G, et al. Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood. 2007;109(11):4635–40.

    Article  PubMed  CAS  Google Scholar 

  54. Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M, et al. Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood. 2004;103(2):473–8.

    Article  PubMed  CAS  Google Scholar 

  55. Helbig G, Moskwa A, Hus M, Piszcz J, Swiderska A, Urbanowicz A, et al. Durable remission after treatment with very low doses of imatinib for FIP1L1-PDGFRalpha-positive chronic eosinophilic leukaemia. Cancer Chemother Pharmacol. 2011;67(4):967–9.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Klion AD, Robyn J, Maric I, Fu W, Schmid L, Lemery S, et al. Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing. Blood. 2007;110(10):3552–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Helbig G, Kyrcz-Krzemien S. Cessation of imatinib mesylate may lead to sustained hematologic and molecular remission in FIP1L1-PDGFRA-mutated hypereosinophilic syndrome. Am J Hematol. 2014;89(1):115.

    Article  PubMed  CAS  Google Scholar 

  58. Legrand F, Renneville A, Macintyre E, Mastrilli S, Ackermann F, Cayuela JM, et al. The spectrum of FIP1L1-PDGFRA-associated chronic eosinophilic leukemia: new insights based on a survey of 44 cases. Medicine (Baltimore). 2013;92(5):e1–e9.

    Article  CAS  Google Scholar 

  59. Helbig G. Imatinib mesylate for unmutated hypereosinophilic syndromes: does it work? Eur J Intern Med. 2016;32:19–20.

    Article  CAS  Google Scholar 

  60. Khoury P, Desmond R, Pabon A, Holland-Thomas N, Ware JM, Arthur DC, et al. Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome. Allergy. 2016;71(6):803–10.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. Lierman E, Cools J. Recent breakthroughs in the understanding and management of chronic eosinophilic leukemia. Expert Rev Anticancer Ther. 2009;9(9):1295–304.

    Article  PubMed  Google Scholar 

  62. Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018;8(2):15.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Johnson DE, O'Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018 (in press);15:234–48.

    Article  PubMed  CAS  Google Scholar 

  64. Schwaab J, Knut M, Haferlach C, Metzgeroth G, Horny HP, Chase A, et al. Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes. Ann Hematol. 2015;94(2):233–8.

    Article  PubMed  CAS  Google Scholar 

  65. Rumi E, Milosevic JD, Casetti I, Dambruoso I, Pietra D, Boveri E, et al. Efficacy of ruxolitinib in chronic eosinophilic leukemia associated with a PCM1-JAK2 fusion gene. J Clin Oncol. 2013;31(17):269–71.

    Article  Google Scholar 

  66. Rumi E, Milosevic JD, Selleslag D, Casetti I, Lierman E, Pietra D, et al. Efficacy of ruxolitinib in myeloid neoplasms with PCM1-JAK2 fusion gene. Ann Hematol. 2015;94(11):1927–8.

    Article  PubMed  Google Scholar 

  67. • King B, Lee AI, Choi J. Treatment of hypereosinophilic syndrome with cutaneous involvement with the JAK inhibitors tofacitinib and ruxolitinib. J Invest Dermatol. 2017;137(4):951–4. This study demonstrated that JAK inhibitors can be effective for the treatment of certain forms of HES.

    Article  PubMed  CAS  Google Scholar 

  68. Roufosse F. Management of hypereosinophilic syndromes. Immunol Allergy Clin N Am. 2015;35(3):561–75.

    Article  Google Scholar 

  69. Gotlib J. World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017;92(11):1243–59.

    Article  PubMed  CAS  Google Scholar 

  70. Cudkowicz M, Bozik ME, Ingersoll EW, Miller R, Mitsumoto H, Shefner J, et al. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med. 2011;17(12):1652–6.

    Article  PubMed  CAS  Google Scholar 

  71. • Dworetzky SI, Hebrank GT, Archibald DG, Reynolds IJ, Farwell W, Bozik ME. The targeted eosinophil-lowering effects of dexpramipexole in clinical studies. Blood Cells Mol Dis. 2017;63:62–5. This study makes the point that an oral agent, dexpramipexole, has a unique and remarkable ability to reduce eosinophil numbers.

    Article  PubMed  CAS  Google Scholar 

  72. Prussin C, Laidlaw TM, Panettieri RA, Ferguson BJ, Adappa ND, Lane AP, et al. Dexpramipexole effectively lowers blood and tissue eosinophils in subjects with chronic rhinosinusitis with nasal polyps. Journal of Allergy and Clinical Immunology. 2017;139(Suppl Feb):AB64.

    Article  Google Scholar 

  73. Nutku E, Aizawa H, Hudson SA, Bochner BS. Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis. Blood. 2003;101(12):5014–20.

    Article  PubMed  CAS  Google Scholar 

  74. Carroll DJ, O'Sullivan JA, Nix DB, Cao Y, Tiemeyer M, Bochner BS. Siglec-8 is an activating receptor mediating beta2 integrin-dependent function in human eosinophils. J Allergy Clin Immunol 2018 (in press).

  75. Youngblood BA, Brock EC, Leung J, Bebbington C, Tomasevic N. Treatment with an anti-Siglec-8 antibody reduces eosinophilic gastrointestinal inflammation in mice. Gordon Research Conference on Food Allergy. 2018; Ventura, CA.

  76. Rasmussen HS, Chang AT, Tomasevic N, Bebbington C. Phase 1 double-blind, placebo-controlled, ascending dose study of Siglec-8 selective mAb AK002 in healthy subjects. J Allergy Clin Immunol. 2018;141(2):AB403.

    Article  Google Scholar 

  77. Hamann J, Koning N, Pouwels W, Ulfman LH, van Eijk M, Stacey M, et al. EMR1, the human homolog of F4/80, is an eosinophil-specific receptor. Eur J Immunol. 2007;37(10):2797–802.

    Article  PubMed  CAS  Google Scholar 

  78. Legrand F, Tomasevic N, Simakova O, Lee CC, Wang Z, Raffeld M, et al. The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders. J Allergy Clin Immunol. 2014;133(5):1439–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Gonem S, Berair R, Singapuri A, Hartley R, Laurencin MFM, Bacher G, et al. Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med. 2016;4(9):699–707.

    Article  PubMed  CAS  Google Scholar 

  80. Straumann A, Hoesli S, Bussmann C, Stuck M, Perkins M, Collins LP, et al. Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy. 2013;68(3):375–85.

    Article  PubMed  CAS  Google Scholar 

  81. Pettipher R, Hunter MG, Perkins CM, Collins LP, Lewis T, Baillet M, et al. Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459. Allergy. 2014;69(9):1223–32.

    Article  PubMed  CAS  Google Scholar 

  82. Korenblat P, Kerwin E, Leshchenko I, Yen K, Holweg CTJ, Anzures-Cabrera J, et al. Efficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma not receiving inhaled corticosteroids. Respir Med. 2018;134:143–9.

    Article  PubMed  Google Scholar 

  83. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088–98.

    Article  PubMed  CAS  Google Scholar 

  84. Molfino NA, Kuna P, Leff JA, Oh CK, Singh D, Chernow M, et al. Phase 2, randomised placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately controlled asthma. BMJ Open. 2016;6(1):007709.

    Article  Google Scholar 

  85. Neighbour H, Boulet LP, Lemiere C, Sehmi R, Leigh R, Sousa AR, et al. Safety and efficacy of an oral CCR3 antagonist in patients with asthma and eosinophilic bronchitis: a randomized, placebo-controlled clinical trial. Clin Exp Allergy. 2014;44(4):508–16.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 E. Huron Street, Room M306, Chicago, IL, 60611, USA

    Melanie C. Dispenza & Bruce S. Bochner

Authors
  1. Melanie C. Dispenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruce S. Bochner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bruce S. Bochner.

Ethics declarations

Conflict of Interest

Dr. Bochner has current or recent consulting or scientific advisory board arrangements with or has received honoraria from Sanofi-Aventis, TEVA, GlaxoSmithKline, AstraZeneca, and Allakos, and owns stock in Allakos. He receives publication-related royalty payments from Elsevier and UpToDate™ and is a co-inventor on existing Siglec-8-related patents and thus may be entitled to a share of royalties received by Johns Hopkins University on the potential sales of such products. Dr. Bochner is also a co-founder of Allakos, which makes him subject to certain restrictions under University policy. The terms of this arrangement are being managed by the Johns Hopkins University and Northwestern University in accordance with their conflict of interest policies. Melanie C. Dispenza declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Myeloproliferative Neoplasms

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dispenza, M.C., Bochner, B.S. Diagnosis and Novel Approaches to the Treatment of Hypereosinophilic Syndromes. Curr Hematol Malig Rep 13, 191–201 (2018). https://doi.org/10.1007/s11899-018-0448-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-018-0448-8

Keywords

Search

Navigation