Hypereosinophilia (HE) is defined as a persistent elevated eosinophil count of ≥1.5 × 109/L. HE can be one of the dominant manifestations of a hematopoietic myeloid neoplasm or secondary/reactive to an underlying medical condition. If a cause of HE and its associated tissue/organ damage is not determined, the condition is considered to be idiopathic hypereosinophilic syndrome (HES). The work-up of HE can be challenging due to a broad range of causes of HE that can be either reactive or neoplastic. In recent years, with the advent of molecular genetic testing and the introduction of targeted therapy in the management of these patients, there is a growing interest in better characterization of these diseases. Using a multimodality approach and following a proper -algorithm, a diagnosis can be made in a large proportion of patients. In idiopathic HES, myeloid neoplasm associated -somatic mutations as evidence of clonality are reported in -20–25% patients; however, the mutation data should be -interpreted cautiously considering the prevalence of clonal hematopoiesis of indeterminate potential (CHIP). Bone marrow morphology has been shown to have important value in the identification of a true myeloid neoplasm in these disorders. A genome-wide study may be needed to understand the “idiopathic” cases that would ultimately lead to better patient care.

1.
Valent P, Klion AD, Horny HP, Roufosse F, Gotlib J, Weller PF, Hellmann A, Metzgeroth G, Leiferman KM, Arock M, Butterfield JH, Sperr WR, Sotlar K, Vandenberghe P, Haferlach T, Simon HU, Reiter A, Gleich GJ: Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol 2012; 130: 607–612.e9.
2.
Reiter A, Gotlib J: Myeloid neoplasms with eosinophilia. Blood 2017; 129: 704–714.
3.
Gleich GJ: Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol 2000; 105: 651–663.
4.
Gotlib J: World Health Organization--defined eosinophilic disorders: 2015 update on diagnosis, risk stratification, and management. Am J Hematol 2015; 90: 1077–1089.
5.
Gotlib J: World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. Am J Hematol 2017; 92: 1243–1259.
6.
Bain BJ, Horny HP, Hasserjian RP, Orazi A: Chronic Eosinophilic Leukaemia, NOS. Lyon France, IARC Press, 2017, pp 54–56.
7.
Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN: Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. Am J Clin Pathol 2015; 144: 377–392.
8.
Jackson CC, Medeiros LJ, Miranda RN: 8p11 myeloproliferative syndrome: a review. Hum Pathol 2010; 41: 461–476.
9.
Bain BJ, Gilliland DG, Horny HP, Vardiman JW: Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA, PDGFRB or FGFR1; in Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (ed): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, International Agency for Research on Cancer (IARC) 2008, pp 68–73.
10.
Tefferi A, Patnaik MM, Pardanani A: Eosinophilia: secondary, clonal and idiopathic. Br J Haematol 2006; 133: 468–492.
11.
Leder K, Weller PF: Eosinophilia and helminthic infections. Baillieres Best Pract Res Clin Haematol 2000; 13: 301–317.
12.
Salas-Coronas J, Cabezas-Fernandez MT, Vazquez-Villegas J, Soriano-Perez MJ, Lozano-Serrano AB, Perez-Camacho I, Cabeza-Barrera MI, Cobo F: Evaluation of eosinophilia in immigrants in Southern Spain using tailored screening and treatment protocols: a prospective study. Travel Med Infect Dis 2015; 13: 315–321.
13.
Choquet-Kastylevsky G, Intrator L, Chenal C, Bocquet H, Revuz J, Roujeau JC: Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome. Br J Dermatol 1998; 139: 1026–1032.
14.
Akcam FZ, Aygun FO, Akkaya VB: DRESS like severe drug rash with eosinophilia, atypic lymphocytosis and fever secondary to ceftriaxone. J Infect 2006; 53:e51–e53.
15.
Bhatt NY, Allen JN: Update on eosinophilic lung diseases. Semin Respir Crit Care Med 2012; 33: 555–571.
16.
Bain GA, Flower CD: Pulmonary eosinophilia. Eur J Radiol 1996; 23: 3–8.
17.
Pagnoux C, Guilpain P, Guillevin L: Churg-Strauss syndrome. Curr Opin Rheumatol 2007; 19: 25–32.
18.
Catovsky D, Bernasconi C, Verdonck PJ, Postma A, Hows J, van der Does-van den Berg A, Rees JK, Castelli G, Morra E, Galton DA: The association of eosinophilia with lymphoblastic leukaemia or lymphoma: a study of seven patients. Br J Haematol 1980; 45: 523–534.
19.
Kawasaki A, Mizushima Y, Matsui S, Hoshino K, Yano S, Kitagawa M: A case of T-cell lymphoma accompanying marked eosinophilia, chronic eosinophilic pneumonia and eosinophilic pleural effusion. A case report. Tumori 1991; 77: 527–530.
20.
Jin JJ, Butterfield JH, Weiler CR: Hematologic malignancies identified in patients with hypereosinophilia and hypereosinophilic syndromes. J Allergy Clin Immunol Pract 2015; 3: 920–925.
21.
Endo M, Usuki K, Kitazume K, Iwabe K, Okuyama Y, Urabe A: Hypereosinophilic syndrome in Hodgkin’s disease with increased granulocyte-macrophage colony-stimulating factor. Ann Hematol 1995; 71: 313–314.
22.
Todenhofer T, Wirths S, von Weyhern CH, Heckl S, Horger M, Hennenlotter J, Stenzl A, Kanz L, Schwentner C: Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma. BMC Urol 2012; 12: 7.
23.
Bank I, Amariglio N, Reshef A, Hardan I, Confino Y, Trau H, Shtrasburg S, Langevitz P, Monselise Y, Shalit M, Rechavi G: The hypereosinophilic syndrome associated with CD4+CD3- helper type 2 (Th2) lymphocytes. Leuk Lymphoma 2001; 42: 123–133.
24.
Simon HU, Plotz SG, Dummer R, Blaser K: Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med 1999; 341: 1112–1120.
25.
Walker S, Wang C, Walradt T, Hong BS, Tanner JR, Levinsohn JL, Goh G, Subtil A, Lessin SR, Heymann WR, Vonderheid EC, King BA, Lifton RP, Choi J: Identification of a gain-of-function STAT3 mutation (p.Y640F) in lymphocytic variant hypereosinophilic syndrome. Blood 2016; 127: 948–951.
26.
Lefevre G, Copin MC, Staumont-Salle D, Avenel-Audran M, Aubert H, Taieb A, Salles G, Maisonneuve H, Ghomari K, Ackerman F, Legrand F, Baruchel A, Launay D, Terriou L, Leclech C, Khouatra C, Morati-Hafsaoui C, Labalette M, Borie R, Cotton F, Gouellec NL, Morschhauser F, Trauet J, Roche-Lestienne C, Capron M, Hatron PY, Prin L, Kahn JE; French Eosinophil Network: The lymphoid variant of hypereosinophilic syndrome: study of 21 patients with CD3-CD4+ aberrant T-cell phenotype. Medicine (Baltimore) 2014; 93: 255–266.
27.
Loghavi S, Wang SA, Medeiros LJ, Jorgensen JL, Li X, Xu-Monette ZY, Miranda RN, Young KH: Immunophenotypic and diagnostic characterization of angioimmunoblastic T-cell lymphoma by advanced flow cytometric technology. Leuk Lymphoma 2016; 57: 2804–2812.
28.
Lefevre G, Copin MC, Roumier C, Aubert H, Avenel-Audran M, Grardel N, Poulain S, Staumont-Salle D, Seneschal J, Salles G, Ghomari K, Terriou L, Leclech C, Morati-Hafsaoui C, Morschhauser F, Lambotte O, Ackerman F, Trauet J, Geffroy S, Dumezy F, Capron M, Roche-Lestienne C, Taieb A, Hatron PY, Dubucquoi S, Hachulla E, Prin L, Labalette M, Launay D, Preudhomme C, Kahn JE; French Eosinophil Network: CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder. Haematologica 2015; 100: 1086–1095.
29.
Brito-Babapulle F: Clonal eosinophilic disorders and the hypereosinophilic syndrome. Blood Rev 1997; 11: 129–145.
30.
Aggrawal DK, Bhargava R, Dolai TK, Singhal D, Mahapatra M, Rathi S, Bohra B, Rathod N: An unusual presentation of eosinophilic variant of chronic myeloid leukemia (eoCML). Ann Hematol 2009; 88: 89–90.
31.
Gotlib V, Darji J, Bloomfield K, Chadburn A, Patel A, Braunschweig I: Eosinophilic variant of chronic myeloid leukemia with vascular complications. Leuk Lymphoma 2003; 44: 1609–1613.
32.
Hendrickson WA, Ward KB: Atomic models for the polypeptide backbones of myohemerythrin and hemerythrin. Biochem Biophys Res Commun 1975; 66: 1349–1356.
33.
Parasole R, Petruzziello F, De Matteo A, Maisto G, Castelli L, Errico ME, Menna G, Poggi V: Hypereosinophilia in childhood acute lymphoblastic leukaemia at diagnosis: report of 2 cases and review of the literature. Ital J Pediatr 2014; 40: 36.
34.
R.P. BBJHHPADATAH: Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement. Lyon, France, IARC Press, 2017.
35.
Gotlib J, Cools J: Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias. Leukemia 2008; 22: 1999–2010.
36.
Vandenberghe P, Wlodarska I, Michaux L, Zachee P, Boogaerts M, Vanstraelen D, Herregods MC, Van Hoof A, Selleslag D, Roufosse F, Maerevoet M, Verhoef G, Cools J, Gilliland DG, Hagemeijer A, Marynen P: Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias. Leukemia 2004; 18: 734–742.
37.
Metzgeroth G, Walz C, Score J, Siebert R, Schnittger S, Haferlach C, Popp H, Haferlach T, Erben P, Mix J, Muller MC, Beneke H, Muller L, Del Valle F, Aulitzky WE, Wittkowsky G, Schmitz N, Schulte C, Muller-Hermelink K, Hodges E, Whittaker SJ, Diecker F, Dohner H, Schuld P, Hehlmann R, Hochhaus A, Cross NC, Reiter A: Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma. Leukemia 2007; 21: 1183–1188.
38.
Schwaab J, Jawhar M, Naumann N, Schmitt-Graeff A, Fabarius A, Horny HP, Cross NC, Hofmann WK, Reiter A, Metzgeroth G: Diagnostic challenges in the work up of hypereosinophilia: pitfalls in bone marrow core biopsy interpretation. Ann Hematol 2016; 95: 557–562.
39.
Schmitt-Graeff AH, Erben P, Schwaab J, Vollmer-Kary B, Metzgeroth G, Sotlar K, Horny HP, Kreipe HH, Fisch P, Reiter A: The FIP1L1-PDGFRA fusion gene and the KIT D816V mutation are coexisting in a small subset of myeloid/lymphoid neoplasms with eosinophilia. Blood 2014; 123: 595–597.
40.
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; 348: 1201–1214.
41.
Curtis CE, Grand FH, Waghorn K, Sahoo TP, George J, Cross NC: A novel ETV6-PDGFRB fusion transcript missed by standard screening in a patient with an imatinib responsive chronic myeloproliferative disease. Leukemia 2007; 21: 1839–1841.
42.
Score J, Curtis C, Waghorn K, Stalder M, Jotterand M, Grand FH, Cross NC: Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia. Leukemia 2006; 20: 827–832.
43.
Walz C, Curtis C, Schnittger S, Schultheis B, Metzgeroth G, Schoch C, Lengfelder E, Erben P, Muller MC, Haferlach T, Hochhaus A, Hehlmann R, Cross NC, Reiter A: Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9; 4) (q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene. Genes Chromosomes Cancer 2006; 45: 950–956.
44.
Chalmers ZR, Ali SM, Ohgami RS, Campregher PV, Frampton GM, Yelensky R, Elvin JA, Palma NA, Erlich R, Vergilio JA, Chmielecki J, Ross JS, Stephens PJ, Hermann R, Miller VA, Miles CR: Comprehensive genomic profiling identifies a novel TNKS2-PDGFRA fusion that defines a myeloid neoplasm with eosinophilia that responded dramatically to imatinib therapy. Blood Cancer J 2015; 5:e278.
45.
Yoshida M, Tamagawa N, Nakao T, Kanashima H, Ueda H, Murakami A, Yorifuji T, Yamane T: Imatinib non-responsive chronic eosinophilic leukemia with ETV6-PDGFRA fusion gene. Leuk Lymphoma 2015; 56: 768–769.
46.
Baxter EJ, Hochhaus A, Bolufer P, Reiter A, Fernandez JM, Senent L, Cervera J, Moscardo F, Sanz MA, Cross NC: The t(4; 22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA. Hum Mol Genet 2002; 11: 1391–1397.
47.
Crescenzi B, Chase A, Starza RL, Beacci D, Rosti V, Galli A, Specchia G, Martelli MF, Vandenberghe P, Cools J, Jones AV, Cross NC, Marynen P, Mecucci C: FIP1L1-PDGFRA in chronic eosinophilic leukemia and BCR-ABL1 in chronic myeloid leukemia affect different leukemic cells. Leukemia 2007; 21: 397–402.
48.
Yigit N, Wu WW, Subramaniyam S, Mathew S, Geyer JT: BCR-PDGFRA fusion in a T lymphoblastic leukemia/lymphoma. Cancer Genet 2015; 208: 404–407.
49.
Trempat P, Villalva C, Laurent G, Armstrong F, Delsol G, Dastugue N, Brousset P: Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor alpha receptor: a new clinical target for STI571/Glivec. Oncogene 2003; 22: 5702–5706.
50.
Roberts KG, Gu Z, Payne-Turner D, McCastlain K, Harvey RC, Chen IM, Pei D, Iacobucci I, Valentine M, Pounds SB, Shi L, Li Y, Zhang J, Cheng C, Rambaldi A, Tosi M, Spinelli O, Radich JP, Minden MD, Rowe JM, Luger S, Litzow MR, Tallman MS, Wiernik PH, Bhatia R, Aldoss I, Kohlschmidt J, Mrozek K, Marcucci G, Bloomfield CD, Stock W, Kornblau S, Kantarjian HM, Konopleva M, Paietta E, Willman CL, Mullighan CG: High frequency and poor outcome of philadelphia chromosome-like acute lymphoblastic leukemia in adults. J Clin Oncol 2017; 35: 394–401.
51.
La Starza R, Specchia G, Cuneo A, Beacci D, Nozzoli C, Luciano L, Aventin A, Sambani C, Testoni N, Foppoli M, Invernizzi R, Marynen P, Martelli MF, Mecucci C: The hypereosinophilic syndrome: fluorescence in situ hybridization detects the del(4)(q12)-FIP1L1/PDGFRA but not genomic rearrangements of other tyrosine kinases. Haematologica 2005; 90: 596–601.
52.
Pardanani A, Ketterling RP, Li CY, Patnaik MM, Wolanskyj AP, Elliott MA, Camoriano JK, Butterfield JH, Dewald GW, Tefferi A: FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature. Leuk Res 2006; 30: 965–970.
53.
Lierman E, Michaux L, Beullens E, Pierre P, Marynen P, Cools J, Vandenberghe P: FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia 2009; 23: 845–851.
54.
Qu SQ, Qin TJ, Xu ZF, Zhang Y, Ai XF, Li B, Zhang HL, Fang LW, Pan LJ, Hu NB, Xiao ZJ: Long-term outcomes of imatinib in patients with FIP1L1/ PDGFRA associated chronic eosinophilic leukemia: experience of a single center in China. Oncotarget 2016; 7: 33229–33236.
55.
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; 92: 1173–1179.
56.
Naumann N, Schwaab J, Metzgeroth G, Jawhar M, Haferlach C, Gohring G, Schlegelberger B, Dietz CT, Schnittger S, Lotfi S, Gartner M, Dang TA, Hofmann WK, Cross NC, Reiter A, Fabarius A: Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms. Genes Chromosomes Cancer 2015; 54: 762–770.
57.
Gosenca D, Kellert B, Metzgeroth G, Haferlach C, Fabarius A, Schwaab J, Kneba M, Scheid C, Topelt K, Erben P, Haferlach T, Cross NC, Hofmann WK, Seifarth W, Reiter A: Identification and functional characterization of imatinib-sensitive DTD1-PDGFRB and CCDC88C-PDGFRB fusion genes in eosinophilia-associated myeloid/lymphoid neoplasms. Genes Chromosomes Cancer 2014; 53: 411–421.
58.
Kim HG, Jang JH, Koh EH: TRIP11-PDGFRB fusion in a patient with a therapy-related myeloid neoplasm with t(5; 14)(q33;q32) after treatment for acute promyelocytic leukemia. Mol Cytogenet 2014; 7: 103.
59.
Walz C, Haferlach C, Hanel A, Metzgeroth G, Erben P, Gosenca D, Hochhaus A, Cross NC, Reiter A: Identification of a MYO18A-PDGFRB fusion gene in an eosinophilia-associated atypical myeloproliferative neoplasm with a t(5; 17)(q33–34;q11.2). Genes Chromosomes Cancer 2009; 48: 179–183.
60.
Zou YS, Hoppman NL, Singh ZN, Sawhney S, Kotiah SD, Baer MR: Novel t(5; 11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with eosinophilia with response to imatinib mesylate. Cancer Genet 2017; 212–213: 38–44.
61.
Kobayashi K, Mitsui K, Ichikawa H, Nakabayashi K, Matsuoka M, Kojima Y, Takahashi H, Iijima K, Ootsubo K, Oboki K, Okita H, Yasuda K, Sakamoto H, Hata K, Yoshida T, Matsumoto K, Kiyokawa N, Ohara A: -ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children. Br J Haematol 2014; 165: 836–841.
62.
Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J, Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS, Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P, Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL, Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrozek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL, Zhang J, Mullighan CG: Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 2014; 371: 1005–1015.
63.
Ondrejka SL, Jegalian AG, Kim AS, Chabot-Richards DS, Giltnane J, Czuchlewski DR, Shetty S, Sekeres MA, Yenamandra A, Head D, Jagasia M, Hsi ED: PDGFRB-rearranged T-lymphoblastic leukemia/lymphoma occurring with myeloid neoplasms: the missing link supporting a stem cell origin. Haematologica 2014; 99:e148–e151.
64.
Arefi M, Garcia JL, Penarrubia MJ, Queizan JA, Hermosin L, Lopez-Corral L, Megido M, Giraldo P, de las Heras N, Vanegas RJ, Gutierrez NC, Hernandez-Rivas JM: Incidence and clinical characteristics of myeloproliferative neoplasms displaying a PDGFRB rearrangement. Eur J Haematol 2012; 89: 37–41.
65.
David M, Cross NC, Burgstaller S, Chase A, Curtis C, Dang R, Gardembas M, Goldman JM, Grand F, Hughes G, Huguet F, Lavender L, McArthur GA, Mahon FX, Massimini G, Melo J, Rousselot P, Russell-Jones RJ, Seymour JF, Smith G, Stark A, Waghorn K, Nikolova Z, Apperley JF: Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 2007; 109: 61–64.
66.
Steer EJ, Cross NC: Myeloproliferative disorders with translocations of chromosome 5q31–35: role of the platelet-derived growth factor receptor Beta. Acta Haematol 2002; 107: 113–122.
67.
Lierman E, Cools J: TV6 and PDGFRB: a license to fuse. Haematologica 2007; 92: 145–147.
68.
Jawhar M, Naumann N, Knut M, Score J, Ghazzawi M, Schneider B, Kreuzer KA, Hallek M, Drexler HG, Chacko J, Wallis L, Fabarius A, Metzgeroth G, Hofmann WK, Chase A, Tapper W, Reiter A, Cross NCP: Cytogenetically cryptic ZMYM2-FLT3 and DIAPH1-PDGFRB gene fusions in myeloid neoplasms with eosinophilia. Leukemia 2017; 31: 2271–2273.
69.
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; 123: 3574–3577.
70.
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; 347: 481–487.
71.
Strati P, Tang G, Duose DY, Mallampati S, Luthra R, Patel KP, Hussaini M, Mirza AS, Komrokji RS, Oh S, Mascarenhas J, Najfeld V, Subbiah V, Kantarjian H, Garcia-Manero G, Verstovsek S, Daver N: Myeloid/lymphoid neoplasms with FGFR1 rearrangement. Leuk Lymphoma 2017;1–5.
72.
Khodadoust MS, Luo B, Medeiros BC, Johnson RC, Ewalt MD, Schalkwyk AS, Bangs CD, Cherry AM, Arai S, Arber DA, Zehnder JL, Gotlib J: Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia. Leukemia 2016; 30: 947–950.
73.
Abruzzo LV, Jaffe ES, Cotelingam JD, Whang-Peng J, Del Duca V Jr, Medeiros LJ: T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol 1992; 16: 236–245.
74.
Wang W, Tang G, Kadia T, Lu X, Li Y, Huang L, Montenegro-Garreaud X, Miranda RN, Wang SA: Cytogenetic evolution associated with disease progression in hematopoietic neoplasms with t(8; 22)(p11;q11)/BCR-FGFR1 rearrangement. J Natl Compr Canc Netw 2016; 14: 708–711.
75.
Montenegro-Garreaud X, Miranda RN, Reynolds A, Tang G, Wang SA, Yabe M, Wang W, Fang L, Bueso-Ramos CE, Lin P, Medeiros LJ, Lu X: Myeloproliferative neoplasms with t(8; 22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase. Hum Pathol 2017; 65: 147–156.
76.
Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O’Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC: The t(8; 9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res 2005; 65: 2662–2667.
77.
Rumi E, Milosevic JD, Selleslag D, Casetti I, Lierman E, Pietra D, Cavalloni C, Bellini M, Milanesi C, Dambruoso I, Astori C, Kralovics R, Vandenberghe P, Cazzola M: Efficacy of ruxolitinib in myeloid neoplasms with PCM1-JAK2 fusion gene. Ann Hematol 2015; 94: 1927–1928.
78.
Weller PF, Bubley GJ: The idiopathic hypereosinophilic syndrome. Blood 1994; 83: 2759–2779.
79.
Bain BJ, Gilliland DG, Vardiman JW, Horny HP: Chronic eosinophilic leukemia, not otherwise specified; in Swerdlow SH, Campo E, Harris NL, et al. (ed): WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues, Lyon, IARC Press, 2008, pp 51–53.
80.
Schwaab J, Umbach R, Metzgeroth G, Naumann N, Jawhar M, Sotlar K, Horny HP, Gaiser T, Hofmann WK, Schnittger S, Cross NC, Fabarius A, Reiter A: KIT D816V and JAK2 V617F mutations are seen recurrently in hypereosinophilia of unknown significance. Am J Hematol 2015; 90: 774–777.
81.
Wang SA, Tam W, Tsai AG, Arber DA, Hasserjian RP, Geyer JT, George TI, Czuchlewski DR, Foucar K, Rogers HJ, Hsi ED, Bryan Rea B, Bagg A, Dal Cin P, Zhao C, Kelley TW, Verstovsek S, Bueso-Ramos C, Orazi A: 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: 854–864.
82.
Lee JS, Seo H, Im K, Park SN, Kim SM, Lee EK, Kim JA, Lee JH, Kwon S, Kim M, Koh I, Hwang S, Park HW, Kang HR, Park KS, Kim JH, Lee DS: Idiopathic hypereosinophilia is clonal disorder? Clonality identified by targeted sequencing. PLoS One 2017; 12: e0185602.
83.
Cargo CA, Rowbotham N, Evans PA, Barrans SL, Bowen DT, Crouch S, Jack AS: Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression. Blood 2015; 126: 2362–2365.
84.
Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL: Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 2015; 126: 9–16.
85.
Wang SA, Hasserjian RP, Tam W, Tsai AG, Geyer JT, George TI, Foucar K, Rogers HJ, Hsi ED, Rea BA, Bagg A, Bueso-Ramos CE, Arber DA, Verstovsek S, Orazi A: Bone marrow morphology is a strong discriminator between chronic eosinophilic leukemia, not otherwise specified and reactive idiopathic hypereosinophilic syndrome. Haematologica 2017; 102: 1352–1360.
86.
Crane MM, Chang CM, Kobayashi MG, Weller PF: Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol 2010; 126: 179–181.
87.
Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous MH, Sheikh J, Simon D, Simon HU, Stein ML, Wardlaw A, Weller PF, Klion AD: Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 2009; 124: 1319–1325.e1313.
88.
Helbig G, Soja A, Bartkowska-Chrobok A, Kyrcz-Krzemien S: Chronic eosinophilic leukemia-not otherwise specified has a poor prognosis with unresponsiveness to conventional treatment and high risk of acute transformation. Am J Hematol 2012; 87: 643–645.
89.
Lefebvre C, Bletry O, Degoulet P, Guillevin L, Bentata-Pessayre M, Le Thi Huong D, Godeau P: (Prognostic factors of hypereosinophilic syndrome. Study of 40 cases). Ann Med Interne (Paris) 1989; 140: 253–257.
90.
Podjasek JC, Butterfield JH: Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature. Leuk Res 2013; 37: 392–395.
91.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391–2405.
92.
Chusid MJ, Dale DC, West BC, Wolff SM: The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore) 1975; 54: 1–27.
93.
Flaum MA, Schooley RT, Fauci AS, Gralnick HR: A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. I. Hematologic manifestations. Blood 1981; 58: 1012–1020.
94.
Kueck BD, Smith RE, Parkin J, Peterson LC, Hanson CA: Eosinophilic leukemia: a myeloproliferative disorder distinct from the hypereosinophilic syndrome. Hematol Pathol 1991; 5: 195–205.
95.
Bain BJ: Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. Br J Haematol 1996; 95: 2–9.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.