{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:59:41Z","timestamp":1788303581894,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Lymphocyte\u2010variant hypereosinophilic syndrome (L\u2010HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin\u20105 (IL\u20105). Treatment is challenging because L\u2010HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L\u2010HES. In all, 25 studies were selected; two were randomised controlled trials of IL\u20105 blockade, which included some patients with L\u2010HES, and the rest were observational studies. Corticosteroids are often used as first\u2010line therapy, but patients with L\u2010HES have lower response rates than other types of HES. Treatments that reduce symptoms and steroid dependence in some patients include interferon\u2010alpha (IFN\u2010\u03b1), anti\u2010IL\u20105 monoclonal antibodies, cyclosporine and mycophenolate. These drugs target T\u2010cell activation and proliferation, or IL\u20105 directly. Although effective, IFN\u2010\u03b1 and cyclosporine were commonly reported to cause side\u2010effects resulting in discontinuation. Alemtuzumab can induce remissions, but these are generally short lived. The anti\u2010IL\u20105 monoclonal antibodies mepolizumab and benralizumab are effective and well tolerated, but with a high rate of relapse once withdrawn. Hydroxyurea, methotrexate, imatinib were unsuccessful in most patients studied. More prospective clinical trials are needed for patients with L\u2010HES.<\/jats:p>","DOI":"10.1111\/bjh.17615","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T12:05:05Z","timestamp":1623240305000},"page":"669-680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Treatment of lymphocyte\u2010variant hypereosinophilic syndrome (L\u2010HES): what to consider after confirming the elusive diagnosis"],"prefix":"10.1111","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9455-8985","authenticated-orcid":false,"given":"Alastair K.","family":"Williams","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of British Columbia Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Dou","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of British Columbia Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-2951","authenticated-orcid":false,"given":"Luke Y. C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology University of British Columbia Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqaa227"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24880"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000088"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000053723"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12842"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13437"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.01.030"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.09.022"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-551614"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2018.04.030"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)01003-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2008.02958.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.4049\/jimmunol.163.10.5624","article-title":"Differential regulation of epithelial\u2010derived C\u2010C chemokine expression by IL\u20104 and the glucocorticoid budesonide","volume":"163","author":"Stellato C","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hemonc.2016.11.001"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01765"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199402243300804"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2017.03.030"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16332"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.06.006"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808010"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23018"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.061390"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.02097.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e318169569a"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.04.033"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1586\/eci.11.27"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.06.049"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2018.04.033"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812185"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05206.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21874"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1302"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2014.007"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2006.10.005"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdcr.2019.05.026"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.10.044"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.04.039"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-02-835330"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2010.02436.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.08.037"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24826"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00570"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.6.2354.bloodjournal8762354"},{"key":"e_1_2_8_45_1","unstructured":"PharmaceuticalsN. (2015).Neoral\/Sandimmune I.V. Dorval QC. Available fromhttps:\/\/www\u2010myrxtx\u2010ca.ezproxy.library.ubc.ca\/search. Accessed 13 February 2021."},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1441"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm1004286"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-06-654277"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805283382206"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.4.1353.bloodjournal8741353"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0371-y"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.08.001"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-0700-2"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-258772"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1997.tb00181.x"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.2.2819"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0374-8"},{"key":"e_1_2_8_58_1","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.4049\/jimmunol.144.6.2109","article-title":"Mechanism of action of cyclosporine A in\u00a0vivo. II. T cell priming in\u00a0vivo to alloantigen can be mediated by an IL\u20102\u2010independent cyclosporine A\u2010resistant pathway","volume":"144","author":"Pereira GM","year":"1990","journal-title":"J Immunol"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780170403"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0268-960X(92)90028-O"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04801.x"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199834050-00002"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0373-9"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.17615","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.17615","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.17615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T08:13:54Z","timestamp":1693210434000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.17615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,8]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1111\/bjh.17615"],"URL":"https:\/\/doi.org\/10.1111\/bjh.17615","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,8]]},"assertion":[{"value":"2021-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}