HemOnc.org - A Hematology Oncology Wiki

Hypereosinophilic syndrome

⬆️ Back to start
Glossary

Note: This page contains a mix of malignant and non-malignant conditions under the common heading of hypereosinophilic syndrome (HES). In the future, we may separate malignancy-associated HES from non-malignant HES.

Portrait of Sanjay R. Mohan, MD, MSCI

Section editor

Sanjay R. Mohan, MD, MSCI
Vanderbilt University
Nashville, TN, USA

Count last updated on :
9 regimens on this page
9 variants on this page


Related pages

Clinical practice guidelines

Given the rapid evolution of evidence in hematology and oncology, any guideline older than five years should be regarded as historical information only.


Regimens for all lines of therapy

Alemtuzumab monotherapy

Regimen details

Summary of evidence
Study Study design
Wagner et al. Case report

Note: Treatment was to be given bi-weekly, exact days were not specified; this is an example. Duration was also not specified.

Targeted therapy

1-week cycles

References

  1. Case report: 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 Jun;123(6):1407-8. Epub 2009 Apr 1. link to original article link to EuroPMC abstract Dosing details in abstract have been reviewed by our editors
  2. Retrospective: Strati P, Cortes J, Faderl S, Kantarjian H, Verstovsek S. Long-term follow-up of patients with hypereosinophilic syndrome treated with Alemtuzumab, an anti-CD52 antibody. Clin Lymphoma Myeloma Leuk. 2013 Jun;13(3):287-91. Epub 2012 Nov 1. link to original article free full text available at EuroPMC link to EuroPMC abstract


Benralizumab monotherapy

Regimen details

Summary of evidence
Study Dates of enrollment Study design Comparator Comparative efficacy
Kuang et al. (NIAID 14-I-0081) to Randomized Phase 2, fewer than 20 pts (E-esc) Placebo Seems to have higher absolute eosinophil count reduction of 50% or more at week 12 (primary endpoint)
Endpoint: 90% vs 30%
Ogbogu et al. (NATRON) to Phase 3 (E-esc) Placebo Most likely has longer time to first HES flare (primary endpoint)
(sHR 0.35, 95% CI, 0.18-0.69)

Note: In NATRON, benralizumab was added to "background therapy" which was not further specified.

Immunosuppressive therapy

4-week cycle for varying durations: six cycles (NATRON); six or more cycles (NIAID 14-I-0081)

References

  1. NIAID 14-I-0081: Kuang FL, Legrand F, Makiya M, Ware J, Wetzler L, Brown T, Magee T, Piligian B, Yoon P, Ellis JH, Sun X, Panch SR, Powers A, Alao H, Kumar S, Quezado M, Yan L, Lee N, Kolbeck R, Newbold P, Goldman M, Fay MP, Khoury P, Maric I, Klion AD. Benralizumab for PDGFRA-negative hypereosinophilic syndrome. N Engl J Med. 2019 Apr 4;380(14):1336-1346. link to original article free full text available at EuroPMC link to EuroPMC abstract link to clinical trial record NCT00001406 Dosing details in manuscript have been reviewed by our editors
  2. NATRON: Ogbogu PU, Roufosse F, Akuthota P, Kuna P, Groh M, Reiter A, Yokota A, Siddiqui SH, Mutsaers PGNJ, Li B, Khoury P, Bahadori LM, Bednarczyk A, Bouma G, Brooks LG, Ferreira J, Grindebacke H, Ho CN, Jain P, Palmer RL, Jison ML, Klion AD; NATRON study group. Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial. Nat Med. 2026 Jun;32(6):2017-2025. Epub 2026 Mar 31. link to original article free full text available at EuroPMC link to EuroPMC abstract link to clinical trial record NCT04191304 Dosing details in manuscript have been reviewed by our editors


Cladribine and Cytarabine

Regimen details

Summary of evidence
Study Dates of enrollment Study design
Jabbour et al. to Phase 2, fewer than 20 pts

Note: The timing of drug administration was in hours in the manuscript, starting at t = 0 hours.

Chemotherapy

3-week cycle, repeated once if PR/CR; refer to the original manuscript for definition of PR

References

  1. Jabbour E, Verstovsek S, Giles F, Gandhi V, Cortes J, O'Brien S, Plunkett W, Garcia-Manero G, Jackson CE, Kantarjian H, Andreeff M. 2-Chlorodeoxyadenosine and cytarabine combination therapy for idiopathic hypereosinophilic syndrome. Cancer. 2005 Aug 1;104(3):541-6. link to original article link to EuroPMC abstract Dosing details in manuscript have been reviewed by our editors


Hydroxyurea monotherapy

Regimen details

Summary of evidence
Study Dates of enrollment Study design
Parrillo et al. to Non-randomized, fewer than 20 pts
Chemotherapy

Continued indefinitely

References

  1. Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med. 1978 Aug;89(2):167-72. link to original article link to EuroPMC abstract Dosing details in manuscript have been reviewed by our editors


Imatinib monotherapy

Regimen details

FDA-recommended dose

Summary of evidence
Study Dates of enrollment Study design
Gleich et al. Not reported Case series
Apperley et al. (STIB2225) Not reported Phase 2, fewer than 20 pts
Pardanani et al. Not reported Phase 2, fewer than 20 pts
Cortes et al. to Phase 2, fewer than 20 pts
Cools et al. to Non-randomized, fewer than 20 pts
Baccarani et al. (HES0203) to Phase 2
Klion et al. 2003 Non-randomized, fewer than 20 pts
Helbig et al. Not reported Non-randomized, fewer than 20 pts
Metzgeroth et al. Not reported Phase 2

Note: Dosing was as described in the Metzgeroth et al. paper.

Targeted therapy
  • Imatinib (Gleevec) PO once per day, with dosing according to the mutation-specific criteria:
    • FIP1L1-PDGFRA fusion positive: 100 mg
    • PDGFRB fusion positive or without known molecular aberration: 400 mg

4-week cycle for 13 or more cycles

Subsequent treatment
  • Helbig et al. : Patients proceeded to imatinib maintenance after 3 to 6 months of therapy which consisted of weekly dosing; dose not specified in the manuscript

References

  1. Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet. 2002 May 4;359(9317):1577-8. link to original article link to EuroPMC abstract
  2. STIB2225: Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE, Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med. 2002 Aug 15;347(7):481-7. link to original article link to EuroPMC abstract Dosing details in abstract have been reviewed by our editors
    1. Pooled update: Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, Ross DM, Forrest D, Genet P, Rousselot P, Patton N, Smith G, Dunbar CE, Ito S, Aguiar RC, Odenike O, Gimelfarb A, Cross NC, Seymour JF. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood. 2014 Jun 5;123(23):3574-7. Epub 2014 Mar 31. link to original article free full text available at EuroPMC link to EuroPMC abstract
  3. Pardanani A, Reeder T, Porrata LF, Li CY, Tazelaar HD, Baxter EJ, Witzig TE, Cross NC, Tefferi A. Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders. Blood. 2003 May 1;101(9):3391-7. Epub 2002 Dec 27. link to original article link to EuroPMC abstract Dosing details in abstract have been reviewed by our editors
  4. Cortes J, Ault P, Koller C, Thomas D, Ferrajoli A, Wierda W, Rios MB, Letvak L, Kaled ES, Kantarjian H. Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome. Blood. 2003 Jun 15;101(12):4714-6. Epub 2003 Feb 20. link to original article link to EuroPMC abstract Dosing details in manuscript have been reviewed by our editors
  5. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R, Gilliland DG. 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 Mar 27;348(13):1201-14. link to original article link to EuroPMC abstract Dosing details in abstract have been reviewed by our editors
  6. Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M, Metcalfe DD, Dunbar C, Nutman TB. Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood. 2004 Jan 15;103(2):473-8. Epub 2003 Sep 22. link to original article link to EuroPMC abstract Dosing details in abstract have been reviewed by our editors
  7. HES0203: Baccarani M, Cilloni D, Rondoni M, Ottaviani E, Messa F, Merante S, Tiribelli M, Buccisano F, Testoni N, Gottardi E, de Vivo A, Giugliano E, Iacobucci I, Paolini S, Soverini S, Rosti G, Rancati F, Astolfi C, Pane F, Saglio G, Martinelli G. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica. 2007 Sep;92(9):1173-9. Epub 2007 Aug 1. link to original article link to EuroPMC abstract link to clinical trial record NCT00276926 Dosing details in abstract have been reviewed by our editors
  8. Helbig G, Stella-Hołowiecka B, Majewski M, Całbecka M, Gajkowska J, Klimkiewicz R, Moskwa A, Grzegorczyk J, Lewandowska M, Hołowiecki J. A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients. Br J Haematol. 2008 Apr;141(2):200-4. Epub 2008 Feb 26. link to original article link to EuroPMC abstract Dosing details in abstract have been reviewed by our editors
  9. Metzgeroth G, Walz C, Erben P, Popp H, Schmitt-Graeff A, Haferlach C, Fabarius A, Schnittger S, Grimwade D, Cross NC, Hehlmann R, Hochhaus A, Reiter A. Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome: a phase-II study. Br J Haematol. 2008 Dec;143(5):707-15. Epub 2008 Oct 17. link to original article link to EuroPMC abstract Dosing details in manuscript have been reviewed by our editors


Mepolizumab monotherapy

Regimen details

Summary of evidence
Study Dates of enrollment Study design Comparator Comparative efficacy
Rothenberg et al. (GSK 100185) to Phase 3 (E-esc) Placebo Most likely has higher reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks (primary endpoint)
Endpoint: 84% vs 43%
(HR 2.90, 95% CI, 1.59-5.26)
Immunosuppressive therapy

3-week cycle for eight cycles

References

  1. GSK 100185: Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28. Epub 2008 Mar 16. Erratum in: N Engl J Med. 2008 Jun 5;358(23): 2530. link to original article link to EuroPMC abstract link to clinical trial record NCT00086658 Dosing details in manuscript have been reviewed by our editors
    1. Update: Roufosse FE, Kahn JE, Gleich GJ, Schwartz LB, Singh AD, Rosenwasser LJ, Denburg JA, Ring J, Rothenberg ME, Sheikh J, Haig AE, Mallett SA, Templeton DN, Ortega HG, Klion AD. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol. 2013 Feb;131(2):461-7.e1-5. Epub 2012 Oct 4. link to original article free full text available at EuroPMC link to EuroPMC abstract


Nilotinib monotherapy

Regimen details

Summary of evidence
Study Dates of enrollment Study design
Hochhaus et al. (A2101--HES substudy) to Phase 1/2, fewer than 20 pts of this subtype
Targeted therapy

4-week cycles

References

  1. A2101--HES substudy: Hochhaus A, le Coutre PD, Kantarjian HM, Baccarani M, Erben P, Reiter A, McCulloch T, Fan X, Novick S, Giles FJ. Effect of the tyrosine kinase inhibitor nilotinib in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia: analysis of the phase 2, open-label, single-arm A2101 study. J Cancer Res Clin Oncol. 2013 Dec;139(12):1985-93. Epub 2013 Sep 22. link to original article free full text available at EuroPMC link to EuroPMC abstract


Peginterferon alfa-2a monotherapy

Regimen details

Summary of evidence
Study Study design
Butterfield et al. Case series

Note: The authors described using peginterferon alfa-2b initially but switched to peginterferon alfa-2a when the first was "no longer available". A range of doses was used."

Immunotherapy

1-week cycles

References

  1. Case series: Butterfield JH, Weiler CR. Use of pegylated interferon in hypereosinophilic syndrome. Leuk Res. 2012 Feb;36(2):192-7. Epub 2011 Nov 26. link to original article link to EuroPMC abstract Dosing details in manuscript have been reviewed by our editors


Ruxolitinib monotherapy

Regimen details

Summary of evidence
Study Study design
Rumi et al. Case report
Biomarker eligibility criteria
  • PCM1-JAK2 fusion
Targeted therapy

Duration not specified

References

  1. Case report: Rumi E, Milosevic JD, Casetti I, Dambruoso I, Pietra D, Boveri E, Boni M, Bernasconi P, Passamonti F, Kralovics R, Cazzola M. Efficacy of ruxolitinib in chronic eosinophilic leukemia associated with a PCM1-JAK2 fusion gene. J Clin Oncol. 2013 Jun 10;31(17):e269-71. Epub 2013 Apr 29. link to original article link to EuroPMC abstract Dosing details in abstract have been reviewed by our editors


Retrieved from "https://hemonc.org/w/index.php?title=Hypereosinophilic_syndrome&oldid=168008"