Difference between revisions of "Hypereosinophilic syndrome"

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!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
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[[#top|Back to Top]]
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|style="background-color:#F0F0F0"|[[File:Sanjay_mohan.png|frameless|upright=0.3|center]]
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</div>
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|<big>[[User:Sanjaymohan|Sanjay R. Mohan, MD, MSCI]]<br>Vanderbilt University<br>Nashville, TN</big>
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{{#lst:Editorial board transclusions|mpn}}
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
|}
 
|}
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''For placebo or observational studies in this condition, please visit [[Hypereosinophilic syndrome - null regimens|this page]].''
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 
==NCCN==
 
==NCCN==
−
*[https://www.nccn.org/professionals/physician_gls/pdf/mlne.pdf NCCN Guidelines - Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes]
+
*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1505 NCCN Guidelines - Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes]
  
 
=All lines of therapy=
 
=All lines of therapy=
 
==Alemtuzumab monotherapy {{#subobject:9207db|Regimen=1}}==
 
==Alemtuzumab monotherapy {{#subobject:9207db|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
 
 
===Regimen {{#subobject:45d126|Variant=1}}===
 
===Regimen {{#subobject:45d126|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.jacionline.org/article/S0091-6749(09)00223-1 Wagner et al. 2009]
+
|[https://doi.org/10.1016/j.jaci.2009.01.069 Wagner et al. 2009]
 
|style="background-color:#ffffbe"|Case report
 
|style="background-color:#ffffbe"|Case report
 
|-
 
|-
 
|}
 
|}
 
''Note: treatment is to be given bi-weekly, exact days not specified; below is an example. Duration also not specified.''
 
''Note: treatment is to be given bi-weekly, exact days not specified; below is an example. Duration also not specified.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Alemtuzumab (Campath)]] 30 mg IV once per day on days 1 & 4
 
*[[Alemtuzumab (Campath)]] 30 mg IV once per day on days 1 & 4
−
 
 
'''7-day cycles'''
 
'''7-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''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. [http://www.jacionline.org/article/S0091-6749(09)00223-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19342084 PubMed]
+
# '''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. [https://doi.org/10.1016/j.jaci.2009.01.069 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19342084/ PubMed]
−
# '''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. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(12)00202-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445419/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23123105 PubMed]
+
# '''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. [https://doi.org/10.1016/j.clml.2012.09.018 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445419/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23123105/ PubMed]
−
 
 
 
==Benralizumab monotherapy {{#subobject:39b68c|Regimen=1}}==
 
==Benralizumab monotherapy {{#subobject:39b68c|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:2gh77d|Variant=1}}===
 
===Regimen {{#subobject:2gh77d|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557265/ Kuang et al. 2019 (NIAID 14-I-0081)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557265/ Kuang et al. 2019 (NIAID 14-I-0081)]
 
|2014-2017
 
|2014-2017
−
| style="background-color:#91cf61" |Randomized Phase 2, <20 pts (E-esc)
+
| style="background-color:#91cf61" |Randomized Phase 2, fewer than 20 pts (E-esc)
−
|[[#Placebo_88|Placebo]]
+
|[[#Placebo|Placebo]]
 
| style="background-color:#91cf60" |Seems to have superior primary endpoint
 
| style="background-color:#91cf60" |Seems to have superior primary endpoint
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Benralizumab (Fasenra)]] 30 mg SC once on day 1
 
*[[Benralizumab (Fasenra)]] 30 mg SC once on day 1
−
 
 
'''28-day cycle for 6 or more cycles'''
 
'''28-day cycle for 6 or more cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# '''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. [https://doi.org/10.1056/NEJMoa1812185 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557265/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30943337 PubMed] NCT00001406
+
# '''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. [https://doi.org/10.1056/NEJMoa1812185 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557265/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30943337/ PubMed] [https://clinicaltrials.gov/study/NCT00001406 NCT00001406]
−
 
 
 
==Cladribine & Cytarabine {{#subobject:b80308|Regimen=1}}==
 
==Cladribine & Cytarabine {{#subobject:b80308|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:d51fc2|Variant=1}}===
 
===Regimen {{#subobject:d51fc2|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.21186/full Jabbour et al. 2005]
+
|[https://doi.org/10.1002/cncr.21186 Jabbour et al. 2005]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
+
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 
|-
 
|-
 
|}
 
|}
−
''Note that the timing of drug administration is in hours in the manuscript, starting at t = 0 hours.''
+
''Note: the timing of drug administration is in hours in the manuscript, starting at t = 0 hours.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Cladribine (Leustatin)]] 12 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 2 (total dose: 60 mg/m<sup>2</sup>)
 
*[[Cladribine (Leustatin)]] 12 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 2 (total dose: 60 mg/m<sup>2</sup>)
 
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 3, 4, 5, 6
 
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 3, 4, 5, 6
−
 
 
'''21-day cycle, repeated once if PR/CR; see text for definition of PR'''
 
'''21-day cycle, repeated once if PR/CR; see text for definition of PR'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# 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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.21186/full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15977212 PubMed]
+
# 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. [https://doi.org/10.1002/cncr.21186 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15977212/ PubMed]
−
 
 
 
==Hydroxyurea monotherapy {{#subobject:e819ce|Regimen=1}}==
 
==Hydroxyurea monotherapy {{#subobject:e819ce|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
 
 
===Regimen {{#subobject:4e5567|Variant=1}}===
 
===Regimen {{#subobject:4e5567|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://annals.org/article.aspx?articleid=692211 Parrillo et al. 1978]
+
|[https://doi.org/10.7326/0003-4819-89-2-167 Parrillo et al. 1978]
−
|style="background-color:#ffffbe"|Non-randomized, <20 pts
+
|style="background-color:#ffffbe"|Non-randomized, fewer than 20 pts
 
|-
 
|-
 
|}
 
|}
−
''To be completed; treatment details are not available in the abstract.''
+
''Note: treatment details are not available in the abstract.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Hydroxyurea (Hydrea)]]
 
*[[Hydroxyurea (Hydrea)]]
−
 
+
</div></div>
 
===References===
 
===References===
−
# Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med. 1978 Aug;89(2):167-72. [http://annals.org/article.aspx?articleid=692211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/677578 PubMed]
+
# Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med. 1978 Aug;89(2):167-72. [https://doi.org/10.7326/0003-4819-89-2-167 link to original article] [https://pubmed.ncbi.nlm.nih.gov/677578/ PubMed]
−
 
 
 
==Imatinib monotherapy {{#subobject:77c7b0|Regimen=1}}==
 
==Imatinib monotherapy {{#subobject:77c7b0|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
 
 
===Regimen {{#subobject:0be8cc|Variant=1}}===
 
===Regimen {{#subobject:0be8cc|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
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|-
 
|-
 
|}
 
|}
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://doi.org/10.1016/S0140-6736(02)08505-7 Gleich et al. 2002]
 
|[https://doi.org/10.1016/S0140-6736(02)08505-7 Gleich et al. 2002]
−
|style="background-color:#ffffbe"|Non-randomized, <20 pts
+
|NR
 +
|style="background-color:#ffffbe"|Case series
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJMoa020150 Apperley et al. 2002]
+
|[https://doi.org/10.1056/NEJMoa020150 Apperley et al. 2002 (STIB2225)]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
+
|NR
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/101/9/3391.long Pardanani et al. 2002]
 
|[http://www.bloodjournal.org/content/101/9/3391.long Pardanani et al. 2002]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
+
|NR
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/101/12/4714.long Cortes et al. 2003]
 
|[http://www.bloodjournal.org/content/101/12/4714.long Cortes et al. 2003]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
+
|2001-2002
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 
|-
 
|-
 
|[https://doi.org/10.1056/NEJMoa025217 Cools et al. 2003]
 
|[https://doi.org/10.1056/NEJMoa025217 Cools et al. 2003]
−
|style="background-color:#ffffbe"|Non-randomized, <20 pts
+
|2001-2002
 +
|style="background-color:#ffffbe"|Non-randomized, fewer than 20 pts
 +
|-
 +
|[http://www.haematologica.org/content/92/9/1173.long Baccarani et al. 2007 (HES0203)]
 +
|2001-2007
 +
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/103/2/473.long Klion et al. 2003]
 
|[http://www.bloodjournal.org/content/103/2/473.long Klion et al. 2003]
−
|style="background-color:#ffffbe"|Non-randomized, <20 pts
+
|2003
−
|-
+
|style="background-color:#ffffbe"|Non-randomized, fewer than 20 pts
−
|[http://www.haematologica.org/content/92/9/1173.long Baccarani et al. 2007]
 
−
|style="background-color:#91cf61"|Phase 2
 
 
|-
 
|-
−
|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2008.07033.x/full Helbig et al. 2008]
+
|[https://doi.org/10.1111/j.1365-2141.2008.07033.x Helbig et al. 2008]
−
|style="background-color:#ffffbe"|Non-randomized, <20 pts
+
|NR
 +
|style="background-color:#ffffbe"|Non-randomized, fewer than 20 pts
 
|-
 
|-
−
|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2008.07294.x/full Metzgeroth et al. 2008]
+
|[https://doi.org/10.1111/j.1365-2141.2008.07294.x Metzgeroth et al. 2008]
 +
|NR
 
|style="background-color:#91cf61"|Phase 2
 
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Dosing is as described in the Metzgeroth et al. 2008 paper.''
+
''Note: Dosing is as described in the Metzgeroth et al. 2008 paper.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Imatinib (Gleevec)]] by the following mutation-specific criteria:
 
*[[Imatinib (Gleevec)]] by the following mutation-specific criteria:
−
**FIP1L1-PDGFRA positive patients: 100 mg PO once per day
+
**FIP1L1-PDGFRA fusion positive: 100 mg PO once per day
 
**PDGFRB fusion positive or without known molecular aberration: 400 mg PO once per day
 
**PDGFRB fusion positive or without known molecular aberration: 400 mg PO once per day
−
 
 
'''28-day cycle for 13 or more cycles'''
 
'''28-day cycle for 13 or more cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
  
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*Helbig et al. 2008: Patients proceeded to a maintenance phase after 3 to 6 months of therapy which consisted of weekly dosing; dose not specified in the manuscript
+
*Helbig et al. 2008: Patients proceeded to [[#Imatinib_monotherapy|imatinib]] maintenance after 3 to 6 months of therapy which consisted of weekly dosing; dose not specified in the manuscript
 +
</div></div>
  
 
===References===
 
===References===
−
# 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. [https://doi.org/10.1016/S0140-6736(02)08505-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12047970 PubMed]
+
# 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. [https://doi.org/10.1016/S0140-6736(02)08505-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12047970/ PubMed]
−
# 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. [https://doi.org/10.1056/NEJMoa020150 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12181402 PubMed]
+
# '''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. [https://doi.org/10.1056/NEJMoa020150 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12181402/ PubMed]
−
## '''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. [http://www.bloodjournal.org/content/123/23/3574.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047496/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687085 PubMed]PubMed PMID: 24687085
+
## '''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. [http://www.bloodjournal.org/content/123/23/3574.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047496/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687085/ PubMed]
−
# 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. [http://www.bloodjournal.org/content/101/9/3391.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12506022 PubMed]
+
# 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. [http://www.bloodjournal.org/content/101/9/3391.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12506022/ PubMed]
−
# 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. [http://www.bloodjournal.org/content/101/12/4714.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12595304 PubMed]  
+
# 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. [http://www.bloodjournal.org/content/101/12/4714.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12595304/ PubMed]  
−
# 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. [https://doi.org/10.1056/NEJMoa025217 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12660384 PubMed]
+
# 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. [https://doi.org/10.1056/NEJMoa025217 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12660384/ PubMed]
−
# 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. [http://www.bloodjournal.org/content/103/2/473.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14504092 PubMed]
+
# 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. [http://www.bloodjournal.org/content/103/2/473.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14504092/ PubMed]
−
# 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. [http://www.haematologica.org/content/92/9/1173.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17666373 PubMed]
+
#'''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. [http://www.haematologica.org/content/92/9/1173.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17666373/ PubMed] [https://clinicaltrials.gov/study/NCT00276926 NCT00276926]
−
# 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2008.07033.x/full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18307562 PubMed]
+
# 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. [https://doi.org/10.1111/j.1365-2141.2008.07033.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18307562/ PubMed]
−
# 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2008.07294.x/full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18950453 PubMed]
+
# 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. [https://doi.org/10.1111/j.1365-2141.2008.07294.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18950453/ PubMed]
  
 
==Mepolizumab monotherapy {{#subobject:39b7a4|Regimen=1}}==
 
==Mepolizumab monotherapy {{#subobject:39b7a4|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:2ef22d|Variant=1}}===
 
===Regimen {{#subobject:2ef22d|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
Line 179: Line 187:
 
|2004-2006
 
|2004-2006
 
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
| style="background-color:#1a9851" |Phase 3 (E-esc)
−
|[[#Placebo_88|Placebo]]
+
|[[#Placebo|Placebo]]
 
| style="background-color:#1a9850" |Superior primary endpoint
 
| style="background-color:#1a9850" |Superior primary endpoint
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Mepolizumab (Nucala)]] 750 mg IV once on day 1
 
*[[Mepolizumab (Nucala)]] 750 mg IV once on day 1
−
 
 
'''21-day cycle for 8 cycles'''
 
'''21-day cycle for 8 cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# '''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. [https://doi.org/10.1056/NEJMoa070812 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18344568 PubMed] NCT00086658
+
# '''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. [https://doi.org/10.1056/NEJMoa070812 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18344568/ PubMed] [https://clinicaltrials.gov/study/NCT00086658 NCT00086658]
−
## '''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. [http://www.jacionline.org/article/S0091-6749(12)01309-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23040887 PubMed]
+
## '''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. [https://doi.org/10.1016/j.jaci.2012.07.055 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3558744/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23040887/ PubMed]
−
 
 
 
==Nilotinib monotherapy {{#subobject:007581|Regimen=1}}==
 
==Nilotinib monotherapy {{#subobject:007581|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:267a4e|Variant=1}}===
 
===Regimen {{#subobject:267a4e|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://doi.org/10.1056/NEJMoa055104 Kantarjian et al. 2006 (A2101)]
 
|[https://doi.org/10.1056/NEJMoa055104 Kantarjian et al. 2006 (A2101)]
−
|style="background-color:#ffffbe"|Phase 1/2, <20 pts of this subtype
+
|2004-2005
 +
|style="background-color:#ffffbe"|Phase 1/2, fewer than 20 pts of this subtype
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Nilotinib (Tasigna)]] 400 mg PO twice per day
+
*[[Nilotinib (Tasigna)]] 400 mg PO twice per day on days 1 to 28
−
 
+
'''28-day cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# '''A2101:''' Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. [https://doi.org/10.1056/NEJMoa055104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16775235 PubMed] NCT00109707
+
# '''A2101:''' Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. [https://doi.org/10.1056/NEJMoa055104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16775235/ PubMed] [https://clinicaltrials.gov/study/NCT00109707 NCT00109707]
−
## '''Subgroup analysis:''' 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. [http://link.springer.com/article/10.1007/s00432-013-1529-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24057647 PubMed]
+
## '''Subgroup analysis:''' 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. [http://link.springer.com/article/10.1007/s00432-013-1529-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5556980/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24057647/ PubMed]
  
 
==Peginterferon alfa-2a monotherapy {{#subobject:010d91|Regimen=1}}==
 
==Peginterferon alfa-2a monotherapy {{#subobject:010d91|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
 
 
===Regimen {{#subobject:72ed60|Variant=1}}===
 
===Regimen {{#subobject:72ed60|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
Line 221: Line 232:
 
|-
 
|-
 
|}
 
|}
−
 
+
''Note: The authors describe using peginterferon alfa-2b initially but switched to peginterferon alfa-2a when the first was "no longer available. Dosing details are not available in the abstract."  
−
''The authors describe using peginterferon alfa-2b initially but switched to peginterferon alfa-2a when the first was "no longer available. Dosing details are not available in the abstract."  
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Peginterferon alfa-2a (Pegasys)]]
 
*[[Peginterferon alfa-2a (Pegasys)]]
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''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. [http://www.lrjournal.com/article/S0145-2126(11)00469-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22118911 PubMed]
+
# '''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. [http://www.lrjournal.com/article/S0145-2126(11)00469-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22118911/ PubMed]
−
 
 
 
==Ruxolitinib monotherapy {{#subobject:87790c|Regimen=1}}==
 
==Ruxolitinib monotherapy {{#subobject:87790c|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
 
 
===Regimen {{#subobject:f86a11|Variant=1}}===
 
===Regimen {{#subobject:f86a11|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
Line 241: Line 250:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Ruxolitinib (Jakafi)]] 15 mg PO twice per day
 
*[[Ruxolitinib (Jakafi)]] 15 mg PO twice per day
−
 
 
'''Duration not specified'''
 
'''Duration not specified'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''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. [https://doi.org/10.1200/jco.2012.46.4370 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23630205 PubMed]
+
# '''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. [https://doi.org/10.1200/jco.2012.46.4370 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23630205/ PubMed]
−
 
 
 
[[Category:Hypereosinophilic syndrome regimens]]
 
[[Category:Hypereosinophilic syndrome regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Myeloproliferative neoplasms]]
 
[[Category:Myeloproliferative neoplasms]]
−
[[Category:Clinical pharmacology]]
 

Revision as of 10:49, 7 May 2024

Back to Top

Section editor
Sanjay mohan.png
 Sanjay R. Mohan, MD, MSCI
Vanderbilt University
Nashville, TN, USA
9 regimens on this page
9 variants on this page

For placebo or observational studies in this condition, please visit this page.


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

All lines of therapy

Alemtuzumab monotherapy

Regimen

Study Evidence
Wagner et al. 2009 Case report

Note: treatment is to be given bi-weekly, exact days not specified; below is an example. Duration also not specified.

Targeted therapy

7-day 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 contains dosing details in abstract PubMed
  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 link to PMC article PubMed

Benralizumab monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Kuang et al. 2019 (NIAID 14-I-0081) 2014-2017 Randomized Phase 2, fewer than 20 pts (E-esc) Placebo Seems to have superior primary endpoint

Immunosuppressive therapy

28-day cycle for 6 or more cycles

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 contains dosing details in manuscript link to PMC article PubMed NCT00001406

Cladribine & Cytarabine

Regimen

Study Evidence
Jabbour et al. 2005 Phase 2, fewer than 20 pts

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

Chemotherapy

21-day cycle, repeated once if PR/CR; see text 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 contains dosing details in manuscript PubMed

Hydroxyurea monotherapy

Regimen

Study Evidence
Parrillo et al. 1978 Non-randomized, fewer than 20 pts

Note: treatment details are not available in the abstract.

Chemotherapy

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 PubMed

Imatinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Gleich et al. 2002 NR Case series
Apperley et al. 2002 (STIB2225) NR Phase 2, fewer than 20 pts
Pardanani et al. 2002 NR Phase 2, fewer than 20 pts
Cortes et al. 2003 2001-2002 Phase 2, fewer than 20 pts
Cools et al. 2003 2001-2002 Non-randomized, fewer than 20 pts
Baccarani et al. 2007 (HES0203) 2001-2007 Phase 2
Klion et al. 2003 2003 Non-randomized, fewer than 20 pts
Helbig et al. 2008 NR Non-randomized, fewer than 20 pts
Metzgeroth et al. 2008 NR Phase 2

Note: Dosing is as described in the Metzgeroth et al. 2008 paper.

Targeted therapy

  • Imatinib (Gleevec) by the following mutation-specific criteria:
    • FIP1L1-PDGFRA fusion positive: 100 mg PO once per day
    • PDGFRB fusion positive or without known molecular aberration: 400 mg PO once per day

28-day cycle for 13 or more cycles

Subsequent treatment

  • Helbig et al. 2008: 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 PubMed
  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 contains dosing details in abstract PubMed
    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 link to PMC article PubMed
  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 contains dosing details in abstract PubMed
  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 contains dosing details in manuscript PubMed
  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 contains dosing details in abstract PubMed
  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 contains dosing details in abstract PubMed
  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 contains dosing details in abstract PubMed NCT00276926
  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 contains dosing details in abstract PubMed
  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 contains dosing details in manuscript PubMed

Mepolizumab monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Rothenberg et al. 2008 (GSK 100185) 2004-2006 Phase 3 (E-esc) Placebo Superior primary endpoint

Immunosuppressive therapy

21-day cycle for 8 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 contains dosing details in manuscript PubMed NCT00086658
    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 link to PMC article PubMed

Nilotinib monotherapy

Regimen

Study Dates of enrollment Evidence
Kantarjian et al. 2006 (A2101) 2004-2005 Phase 1/2, fewer than 20 pts of this subtype

Targeted therapy

28-day cycles

References

  1. A2101: Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. link to original article PubMed NCT00109707
    1. Subgroup analysis: 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 link to PMC article PubMed

Peginterferon alfa-2a monotherapy

Regimen

Study Evidence
Butterfield et al. 2011 Case series

Note: The authors describe using peginterferon alfa-2b initially but switched to peginterferon alfa-2a when the first was "no longer available. Dosing details are not available in the abstract."

Immunotherapy

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 PubMed

Ruxolitinib monotherapy

Regimen

Study Evidence
Rumi et al. 2013 Case report

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 contains dosing details in abstract PubMed
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