View source for HAEM4Backup:Myeloid/Lymphoid Neoplasms with PDGFRA Rearrangement

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==Primary Author(s)*==

Jay Alden, DO

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==Cancer Category/Type==

Acute Myeloid Leukemia/Myeloid/lymphoid neoplasms 

==Cancer Sub-Classification / Subtype==

Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement

==Definition / Description of Disease==

Myeloproliferative neoplasms associated with PDGFRA rearrangements are primary/neoplastic hypereosinophilic syndromes associated with recurrent rearrangements of the PDGFRA gene <ref name=":0">Bain BJ, et al., (2017). Myeloid/lymphoid neoplasms with PDGFRA rearrangement in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p73-75.</ref>. It is most commonly associated with FIP1L1-PDGFRA (F/P) fusion resulting from a cryptic deletion at 4q12, <ref name=":5">{{Cite journal|last=Cools|first=Jan|last2=DeAngelo|first2=Daniel J.|last3=Gotlib|first3=Jason|last4=Stover|first4=Elizabeth H.|last5=Legare|first5=Robert D.|last6=Cortes|first6=Jorges|last7=Kutok|first7=Jeffrey|last8=Clark|first8=Jennifer|last9=Galinsky|first9=Ilene|date=2003|title=A Tyrosine Kinase Created by Fusion of the PDGFRA and FIP1L1 Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome|url=http://www.nejm.org/doi/abs/10.1056/NEJMoa025217|journal=New England Journal of Medicine|language=en|volume=348|issue=13|pages=1201–1214|doi=10.1056/NEJMoa025217|issn=0028-4793}}</ref> and often presents as chronic eosinophilic leukemia (CEL), or less commonly, acute myeloid leukemia or T-lymphoblastic leukemia/lymphoma. <ref name=":1">{{Cite journal|last=Metzgeroth|first=G.|last2=Walz|first2=C.|last3=Score|first3=J.|last4=Siebert|first4=R.|last5=Schnittger|first5=S.|last6=Haferlach|first6=C.|last7=Popp|first7=H.|last8=Haferlach|first8=T.|last9=Erben|first9=P.|date=2007|title=Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/17377585|journal=Leukemia|volume=21|issue=6|pages=1183–1188|doi=10.1038/sj.leu.2404662|issn=0887-6924|pmid=17377585}}</ref>

==Synonyms / Terminology==

Chronic eosinophilic leukemia with FIP1L1-PDGFRA

''FIP1L1-PDGFRA'' –associated chronic eosinophilic leukemia

Myeloid and lymphoid neoplasms associated with PDGFRA rearrangement

PDGFRA-associated Hypereosinophilic syndrome

Myeloid and lymphoid neoplasms with PDGFRA rearrangement

Myeloproliferative variant of the hypereosinophilic syndrome <ref name=":2">{{Cite journal|last=Klion|first=Amy D.|last2=Robyn|first2=Jamie|last3=Akin|first3=Cem|last4=Noel|first4=Pierre|last5=Brown|first5=Margaret|last6=Law|first6=Melissa|last7=Metcalfe|first7=Dean D.|last8=Dunbar|first8=Cynthia|last9=Nutman|first9=Thomas B.|date=2004|title=Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/14504092|journal=Blood|volume=103|issue=2|pages=473–478|doi=10.1182/blood-2003-08-2798|issn=0006-4971|pmid=14504092}}</ref>

==Epidemiology / Prevalence==

The incidence and prevalence of myeloid/lymphoid neoplasms with PDGFRA rearrangement is not well characterized as demographic data is scarce <ref name=":6">{{Cite journal|last=Shomali|first=William|last2=Gotlib|first2=Jason|date=2019|title=World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management|url=https://www.ncbi.nlm.nih.gov/pubmed/31423623|journal=American Journal of Hematology|volume=94|issue=10|pages=1149–1167|doi=10.1002/ajh.25617|issn=1096-8652|pmid=31423623}}</ref>. The incidence of HES of any cause is estimated at 0.036 per 100,000, <ref>{{Cite journal|last=Crane|first=Martin M.|last2=Chang|first2=Cindy Ma|last3=Kobayashi|first3=Monica G.|last4=Weller|first4=Peter F.|date=2010|title=Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence|url=https://www.ncbi.nlm.nih.gov/pubmed/20639012|journal=The Journal of Allergy and Clinical Immunology|volume=126|issue=1|pages=179–181|doi=10.1016/j.jaci.2010.03.035|issn=1097-6825|pmc=5781228|pmid=20639012}}</ref> though cases in which a causative genetic abnormality constitute a minority of these cases <ref name=":6" />. The F/P rearrangement  is the most common abnormality identified, and is estimated to comprise approximately 10%  of patients with significant hypereosinophilia <ref>{{Cite journal|last=Pardanani|first=Animesh|last2=Brockman|first2=Stephanie R.|last3=Paternoster|first3=Sarah F.|last4=Flynn|first4=Heather C.|last5=Ketterling|first5=Rhett P.|last6=Lasho|first6=Terra L.|last7=Ho|first7=Ching-Liang|last8=Li|first8=Chin-Yang|last9=Dewald|first9=Gordon W.|date=2004|title=FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia|url=https://www.ncbi.nlm.nih.gov/pubmed/15284118|journal=Blood|volume=104|issue=10|pages=3038–3045|doi=10.1182/blood-2004-03-0787|issn=0006-4971|pmid=15284118}}</ref> <ref>{{Cite journal|last=Pardanani|first=A.|last2=Ketterling|first2=R. P.|last3=Li|first3=C.-Y.|last4=Patnaik|first4=M. M.|last5=Wolanskyj|first5=A. P.|last6=Elliott|first6=M. A.|last7=Camoriano|first7=J. K.|last8=Butterfield|first8=J. H.|last9=Dewald|first9=G. W.|date=2006|title=FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature|url=https://www.ncbi.nlm.nih.gov/pubmed/16406016|journal=Leukemia Research|volume=30|issue=8|pages=965–970|doi=10.1016/j.leukres.2005.11.011|issn=0145-2126|pmid=16406016}}</ref>. The entity is recently described, and disorders once called idiopathic hypereosinophilic syndrome are now being classified with genetic testing as specific primary neoplasms  or reactive conditions. The  F/P rearrangment is significantly more common in males with a male:female ratio of about 17:1. The age range varies from ages 7-77 with most patients being between 25 and 55 years. <ref>{{Cite journal|last=Bain|first=Barbara J.|last2=Fletcher|first2=Sarah H.|date=2007|title=Chronic eosinophilic leukemias and the myeloproliferative variant of the hypereosinophilic syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17868855|journal=Immunology and Allergy Clinics of North America|volume=27|issue=3|pages=377–388|doi=10.1016/j.iac.2007.06.001|issn=0889-8561|pmid=17868855}}</ref>

==Clinical Features==

Clinical presentation ranges from asymptomatic to fulminant, life threatening multi-system organ failure. Presenting signs and symptoms are typically related to eosinophilic infiltration, and consistent with hypereosinophilic syndromes of any cause. The largest clinical analysis of patients with hypereosinophilic syndromes (HES) demonstrated the following manifestations at presentation:<ref>{{Cite journal|last=Ogbogu|first=Princess U.|last2=Bochner|first2=Bruce S.|last3=Butterfield|first3=Joseph H.|last4=Gleich|first4=Gerald J.|last5=Huss-Marp|first5=Johannes|last6=Kahn|first6=Jean Emmanuel|last7=Leiferman|first7=Kristin M.|last8=Nutman|first8=Thomas B.|last9=Pfab|first9=Florian|date=2009|title=Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy|url=https://www.ncbi.nlm.nih.gov/pubmed/19910029|journal=The Journal of Allergy and Clinical Immunology|volume=124|issue=6|pages=1319–1325.e3|doi=10.1016/j.jaci.2009.09.022|issn=1097-6825|pmc=2829669|pmid=19910029}}</ref>

*Dermatologic (eg, rash) – 57 percent
*Pulmonary (cough and breathlessness) – 25 percent
*Gastrointestinal – 14 percent
*Cardiac – <5 percent
*Asymptomatic -- 6 percent

Neoplastic PDGFRA-associated hypereosinophilic syndromes are more likely to present with eosinophilic cardiopulmonary disease than HES of any cause. A survey of 44 cases demonstrated skin, spleen, lung, and heart involvement in 57, 52, 45, and 34 percent of cases respectively with a similar rate of asymptomatic cases. <ref name=":8">{{Cite journal|last=Legrand|first=Fanny|last2=Renneville|first2=Aline|last3=MacIntyre|first3=Elizabeth|last4=Mastrilli|first4=Samuel|last5=Ackermann|first5=Felix|last6=Cayuela|first6=Jean Michel|last7=Rousselot|first7=Philippe|last8=Schmidt-Tanguy|first8=Aline|last9=Fain|first9=Olivier|date=2013|title=The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia: New Insights Based on a Survey of 44 Cases|url=https://www.ncbi.nlm.nih.gov/pubmed/23982058|journal=Medicine|volume=92|issue=5|pages=e1–e9|doi=10.1097/MD.0b013e3182a71eba|issn=1536-5964|pmc=4553979|pmid=23982058}}</ref> 

==Sites of Involvement==

Leukemia associated with F/P is a systemic disease occupying the bone marrow and peripheral blood. Neoplastic cells may infiltrate various tissues such as the heart, lungs, nervous systems, skin and GI tract resulting in degranulation and cytokine mediated injury. <ref name=":0" />

==Morphologic Features==
[[File:1-2.jpg|thumb|Hematoxylin and Eosin stained endomyocardial biopsy showing eosinophilic infiltration of endocardium in eosinophilic myocarditis]]
Histopathologic features are dependent on the organs involved. Eosinophilic infiltration is noted on diagnostic tissue biopsy. Eosinophilia and increased eosinophilic precursors can be identified on trephine bone marrow biopsy and peripheral blood smears. There is no histologic correlate to clonality, and genetic studies are required for diagnosis. 
[[File:1-14.jpg|thumb|Hematoxylin and Eosin stained section of bone marrow showing increased eosinophils and eosinophilic precursors]]

==Immunophenotype==

These neoplastic eosinophils may express markers of activation such as CD23, CD25, and CD69<ref name=":2" />. The basophils can sometimes be distinguished from those in systemic mastocytosis as CD2 is typically negative in the mast cells of PDGFRA rearrangement, but positive in systemic mastocytosis. <ref name=":3">{{Cite journal|last=Klion|first=Amy D.|last2=Noel|first2=Pierre|last3=Akin|first3=Cem|last4=Law|first4=Melissa A.|last5=Gilliland|first5=D. Gary|last6=Cools|first6=Jan|last7=Metcalfe|first7=Dean D.|last8=Nutman|first8=Thomas B.|date=2003|title=Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness|url=https://www.ncbi.nlm.nih.gov/pubmed/12676775|journal=Blood|volume=101|issue=12|pages=4660–4666|doi=10.1182/blood-2003-01-0006|issn=0006-4971|pmid=12676775}}</ref><ref name=":1" />

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (subset)||CD25 <ref name=":2" />
|-
|Positive (subset)
|CD23 <ref name=":2" />
|-
|Positive (subset)||CD69 <ref name=":2" />
|-
|Negative (Mast cells)||CD2 <ref name=":3" /><ref name=":1" />
|-
|Posivite (Mast cells, subset
|CD25 <ref name=":3" /><ref name=":1" />
|}

==Chromosomal Rearrangements (Gene Fusions)==

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Prevalence
|-
|Cryptic del(4)(q12)||FIP1L1-PDGFRA||Majority
|-
|T(1;4) (q44;q12)
|FIP1L1-PDGFRA
|Rare <ref name=":4">{{Cite journal|last=Cools|first=Jan|last2=DeAngelo|first2=Daniel J.|last3=Gotlib|first3=Jason|last4=Stover|first4=Elizabeth H.|last5=Legare|first5=Robert D.|last6=Cortes|first6=Jorges|last7=Kutok|first7=Jeffrey|last8=Clark|first8=Jennifer|last9=Galinsky|first9=Ilene|date=2003|title=A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12660384|journal=The New England Journal of Medicine|volume=348|issue=13|pages=1201–1214|doi=10.1056/NEJMoa025217|issn=1533-4406|pmid=12660384}}</ref>
|-
|T(4;10)(q12;p11.1-p11.2)
|FIP1L1-PDGFRA
|Rare <ref>{{Cite journal|last=Tashiro|first=Haruko|last2=Shirasaki|first2=Ryosuke|last3=Noguchi|first3=Mitsuho|last4=Gotoh|first4=Moritaka|last5=Kawasugi|first5=Kazuo|last6=Shirafuji|first6=Naoki|date=2006|title=Molecular analysis of chronic eosinophilic leukemia with t(4;10) showing good response to imatinib mesylate|url=https://www.ncbi.nlm.nih.gov/pubmed/16787876|journal=International Journal of Hematology|volume=83|issue=5|pages=433–438|doi=10.1532/IJH97.05180|issn=0925-5710|pmid=16787876}}</ref>
|-
|T(4;22)(q12;q11.2)
|BCR-PDGFRA
|At least 9 cases <ref>{{Cite journal|last=Baxter|first=E. Joanna|last2=Hochhaus|first2=Andreas|last3=Bolufer|first3=Pascual|last4=Reiter|first4=Andreas|last5=Fernandez|first5=José M.|last6=Senent|first6=Leonor|last7=Cervera|first7=José|last8=Moscardo|first8=Federico|last9=Sanz|first9=Miguel A.|date=2002|title=The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA|url=https://www.ncbi.nlm.nih.gov/pubmed/12023981|journal=Human Molecular Genetics|volume=11|issue=12|pages=1391–1397|doi=10.1093/hmg/11.12.1391|issn=0964-6906|pmid=12023981}}</ref><ref>{{Cite journal|last=Van Etten|first=Richard A.|last2=Cross|first2=Nicholas C. P.|last3=Gavrilescu|first3=L. Cristina|date=2006|title=Distinct Leukemogenic Activity and Imatinib Responsiveness of a BCR-PFGFRα Fusion Tyrosine Kinase.|url=https://ashpublications.org/blood/article/108/11/3634/127080/Distinct-Leukemogenic-Activity-and-Imatinib|journal=Blood|language=en|volume=108|issue=11|pages=3634–3634|doi=10.1182/blood.V108.11.3634.3634|issn=0006-4971}}</ref><ref>{{Cite journal|last=Safley|first=Anne Michele|last2=Sebastian|first2=Siby|last3=Collins|first3=Timothy S.|last4=Tirado|first4=Carlos A.|last5=Stenzel|first5=Timothy T.|last6=Gong|first6=Jerald Z.|last7=Goodman|first7=Barbara K.|date=2004|title=Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with atypical chronic myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/15034867|journal=Genes, Chromosomes & Cancer|volume=40|issue=1|pages=44–50|doi=10.1002/gcc.20014|issn=1045-2257|pmid=15034867}}</ref><ref>{{Cite journal|last=Trempat|first=Pascal|last2=Villalva|first2=Claire|last3=Laurent|first3=Guy|last4=Armstrong|first4=Florence|last5=Delsol|first5=Georges|last6=Dastugue|first6=Nicole|last7=Brousset|first7=Pierre|date=2003|title=Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor alpha receptor: a new clinical target for STI571/Glivec|url=https://www.ncbi.nlm.nih.gov/pubmed/12944919|journal=Oncogene|volume=22|issue=36|pages=5702–5706|doi=10.1038/sj.onc.1206543|issn=0950-9232|pmid=12944919}}</ref>
|-
|T(2;4)(p24;q12)
|STRN-PDGFRA
|At least 1 case <ref name=":7">{{Cite journal|last=Curtis|first=Claire E.|last2=Grand|first2=Francis H.|last3=Musto|first3=Pellegrino|last4=Clark|first4=Andrew|last5=Murphy|first5=John|last6=Perla|first6=Gianni|last7=Minervini|first7=Maria M.|last8=Stewart|first8=Janet|last9=Reiter|first9=Andreas|date=2007|title=Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic leukaemia|url=https://www.ncbi.nlm.nih.gov/pubmed/17555450|journal=British Journal of Haematology|volume=138|issue=1|pages=77–81|doi=10.1111/j.1365-2141.2007.06628.x|issn=0007-1048|pmid=17555450}}</ref>
|-
|T(4;12)(q12;p13.2)
|ETV6-PDGFRA
|At least 1 case <ref name=":7" />
|-
|ins(9;4)(q33;q12q25)
|CDK5RAP2-PDGFRA
|At least 1 case <ref>{{Cite journal|last=Walz|first=Christoph|last2=Curtis|first2=Claire|last3=Schnittger|first3=Susanne|last4=Schultheis|first4=Beate|last5=Metzgeroth|first5=Georgia|last6=Schoch|first6=Claudia|last7=Lengfelder|first7=Eva|last8=Erben|first8=Philipp|last9=Müller|first9=Martin C.|date=2006|title=Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene|url=https://www.ncbi.nlm.nih.gov/pubmed/16845659|journal=Genes, Chromosomes & Cancer|volume=45|issue=10|pages=950–956|doi=10.1002/gcc.20359|issn=1045-2257|pmid=16845659}}</ref>
|-
|T(4;10)(q12;q23.3)
|TNKS2-PDGFRA
|At least 1 case <ref>{{Cite journal|last=Chalmers|first=Z. R.|last2=Ali|first2=S. M.|last3=Ohgami|first3=R. S.|last4=Campregher|first4=P. V.|last5=Frampton|first5=G. M.|last6=Yelensky|first6=R.|last7=Elvin|first7=J. A.|last8=Palma|first8=N. A.|last9=Erlich|first9=R.|date=2015|title=Comprehensive genomic profiling identifies a novel TNKS2-PDGFRA fusion that defines a myeloid neoplasm with eosinophilia that responded dramatically to imatinib therapy|url=https://www.ncbi.nlm.nih.gov/pubmed/25658984|journal=Blood Cancer Journal|volume=5|pages=e278|doi=10.1038/bcj.2014.95|issn=2044-5385|pmc=4349257|pmid=25658984}}</ref>
|}		
			
==Characteristic Chromosomal Aberrations / Patterns==

Cytogenetic studies are usually normal though trisomy of chromosome 8 has been described, and may represent disease evolution <ref name=":0" />.

==Gene Mutations (SNV/INDEL)==

An activating point mutation in PDGFRA has also been described <ref>{{Cite journal|last=Elling|first=Christian|last2=Erben|first2=Philipp|last3=Walz|first3=Christoph|last4=Frickenhaus|first4=Marie|last5=Schemionek|first5=Mirle|last6=Stehling|first6=Martin|last7=Serve|first7=Hubert|last8=Cross|first8=Nicholas C. P.|last9=Hochhaus|first9=Andreas|date=2011|title=Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease|url=https://www.ncbi.nlm.nih.gov/pubmed/21224473|journal=Blood|volume=117|issue=10|pages=2935–2943|doi=10.1182/blood-2010-05-286757|issn=1528-0020|pmid=21224473}}</ref>.
==Genes and Main Pathways Involved==

the F/P tyrosine kinase is thought to become constitutively active in the setting of PDGRA juxtamembrane interruption as breakpoints in the PDGRA gene are tightly clustered, resulting in the removal of a portion of the juxtamembrane domain and activation of the kinase domain upon rearrangement. The role of the FIP1L1 in the neoplastic process is thought to be less significant. <ref>{{Cite journal|last=J. Cools|last2=Gotlib|first2=J.|date=2008|title=Five years since the discovery of FIP1L1–PDGFRA : what we have learned about the fusion and other molecularly defined eosinophilias|url=https://www.nature.com/articles/leu2008287|journal=Leukemia|language=en|volume=22|issue=11|pages=1999–2010|doi=10.1038/leu.2008.287|issn=1476-5551}}</ref>  The eosinophilic proliferation observed in these patients is thought to result from multiple signalling pathways including phosphoinositol 3-kinase, ERK 1/2 and STAT5, though the precise mechanism remains elusive. <ref name=":5" /><ref>{{Cite journal|last=Buitenhuis|first=Miranda|last2=Verhagen|first2=Liesbeth P.|last3=Cools|first3=Jan|last4=Coffer|first4=Paul J.|date=2007|title=Molecular mechanisms underlying FIP1L1-PDGFRA-mediated myeloproliferation|url=https://www.ncbi.nlm.nih.gov/pubmed/17440089|journal=Cancer Research|volume=67|issue=8|pages=3759–3766|doi=10.1158/0008-5472.CAN-06-4183|issn=0008-5472|pmid=17440089}}</ref>

==Diagnostic Testing Methods==

Myeloid/lymphoid neoplasms with PDGFRA are diagnosed with a combination of morphologic, immunophenotypic and genomic modalities; typically with a bone marrow biopsy and peripheral blood smear review, preferably drawn prior to administration of high dose corticosteroids. Additional studies performed at the time of workup include CBC to quantify any abnormalities in other cell lines, tests of hepatic and renal function, troponin for evidence of myocarditis, vitamin B12, serum tryptase, antineutrophil cytoplasmic antibodies, and a high resolution chest CT for evidence of pulmonary involvement. <ref>Rosemarin, A, and Feldweg, A. Hypereosinophilic syndromes: Treatement. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA. April 2020</ref> The diagnosis is made when the F/P fusion gene or a variant fusion gene with rearrangement of PDGFRA or an activating mutation of PDGFRA is identified in the setting of a myeloid or lymphoid neoplasm, usually with prominent eosinophilia <ref name=":0" />. 

The F/P fusion gene can be detected by reverse transcriptase PCR (RT-PCR) <ref name=":4" />, or the deletion can be detected using a probe for the CHIC2 gene, or with a break apart probe encompassing FIP1L1 and PDGFRA. <ref name=":0" /> 

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

The responsiveness of F/P associated myeloid/lymphoid neoplasms to imatinib mesylate is well documented <ref name=":6" />.  Adverse outcomes are typically related to late presentation, where irreversible organ damage precedes diagnosis, or when the disease is diagnosed in an accelerated phase when complications are more likely. Induction dosing of imatinib ranges from 100-400 mg daily, with much lower maintenence dosing recommended to prevent relapse <ref>{{Cite journal|last=Baccarani|first=Michele|last2=Cilloni|first2=Daniela|last3=Rondoni|first3=Michela|last4=Ottaviani|first4=Emanuela|last5=Messa|first5=Francesca|last6=Merante|first6=Serena|last7=Tiribelli|first7=Mario|last8=Buccisano|first8=Francesco|last9=Testoni|first9=Nicoletta|date=2007|title=The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study|url=https://www.ncbi.nlm.nih.gov/pubmed/17666373|journal=Haematologica|volume=92|issue=9|pages=1173–1179|doi=10.3324/haematol.11420|issn=1592-8721|pmid=17666373}}</ref> <ref>{{Cite journal|last=Jovanovic|first=Jelena V.|last2=Score|first2=Joannah|last3=Waghorn|first3=Katherine|last4=Cilloni|first4=Daniela|last5=Gottardi|first5=Enrico|last6=Metzgeroth|first6=Georgia|last7=Erben|first7=Philipp|last8=Popp|first8=Helena|last9=Walz|first9=Christoph|date=2007|title=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|url=https://www.ncbi.nlm.nih.gov/pubmed/17299092|journal=Blood|volume=109|issue=11|pages=4635–4640|doi=10.1182/blood-2006-10-050054|issn=0006-4971|pmid=17299092}}</ref>. Complete hematologic and molecular remission is observed in nearly all patients taking imatinib, usually within 3 months. <ref>{{Cite journal|last=Baccarani|first=Michele|last2=Cilloni|first2=Daniela|last3=Rondoni|first3=Michela|last4=Ottaviani|first4=Emanuela|last5=Messa|first5=Francesca|last6=Merante|first6=Serena|last7=Tiribelli|first7=Mario|last8=Buccisano|first8=Francesco|last9=Testoni|first9=Nicoletta|date=2007|title=The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study|url=https://www.ncbi.nlm.nih.gov/pubmed/17666373|journal=Haematologica|volume=92|issue=9|pages=1173–1179|doi=10.3324/haematol.11420|issn=1592-8721|pmid=17666373}}</ref> <ref>{{Cite journal|last=Quéméneur|first=Thomas|last2=Mouthon|first2=Luc|last3=Cacoub|first3=Patrice|last4=Meyer|first4=Olivier|last5=Michon-Pasturel|first5=Ulrique|last6=Vanhille|first6=Philippe|last7=Hatron|first7=Pierre-Yves|last8=Guillevin|first8=Loïc|last9=Hachulla|first9=Eric|date=2013|title=Systemic vasculitis during the course of systemic sclerosis: report of 12 cases and review of the literature|url=https://www.ncbi.nlm.nih.gov/pubmed/23263715|journal=Medicine|volume=92|issue=1|pages=1–9|doi=10.1097/MD.0b013e31827781fd|issn=1536-5964|pmc=5370746|pmid=23263715}}</ref> <ref>{{Cite journal|last=Helbig|first=Grzegorz|last2=Stella-Hołowiecka|first2=Beata|last3=Majewski|first3=Mirosław|last4=Całbecka|first4=Małgorzata|last5=Gajkowska|first5=Jolanta|last6=Klimkiewicz|first6=Ryszard|last7=Moskwa|first7=Andrzej|last8=Grzegorczyk|first8=Janina|last9=Lewandowska|first9=Monika|date=2008|title=A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients|url=https://www.ncbi.nlm.nih.gov/pubmed/18307562|journal=British Journal of Haematology|volume=141|issue=2|pages=200–204|doi=10.1111/j.1365-2141.2008.07033.x|issn=1365-2141|pmid=18307562}}</ref> Imatinib maintains efficacy in accelerated or blast phase disease, and resistance is rare <ref name=":8" /> <ref>{{Cite journal|last=Lierman|first=E.|last2=Michaux|first2=L.|last3=Beullens|first3=E.|last4=Pierre|first4=P.|last5=Marynen|first5=P.|last6=Cools|first6=J.|last7=Vandenberghe|first7=P.|date=2009|title=FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib|url=https://www.ncbi.nlm.nih.gov/pubmed/19212337|journal=Leukemia|volume=23|issue=5|pages=845–851|doi=10.1038/leu.2009.2|issn=1476-5551|pmid=19212337}}</ref>.

==Familial Forms==

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==Other Information==

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==Links==

[[PDGFRA]]

==References==
<references />

==Notes==
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