{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:22:04Z","timestamp":1792588924424,"version":"4.5.0"},"reference-count":16,"publisher":"American Society of Hematology","issue":"1","license":[{"start":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T00:00:00Z","timestamp":1713657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist, in participants with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by CXCR4 gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged \u226512 years with WHIM syndrome and absolute neutrophil count (ANC) \u22640.4 \u00d7 103\/\u03bcL. Participants received once-daily mavorixafor or placebo for 52 weeks. The primary end point was time (hours) above ANC threshold \u22650.5 \u00d7 103\/\u03bcL (TATANC; over 24 hours). Secondary end points included TAT absolute lymphocyte count \u22651.0 \u00d7 103\/\u03bcL (TATALC; over 24 hours); absolute changes in white blood cell (WBC), ANC, and absolute lymphocyte count (ALC) from baseline; annualized infection rate; infection duration; and total infection score (combined infection number\/severity). In 31 participants (mavorixafor, n\u00a0= 14; placebo, n\u00a0= 17), mavorixafor least squares (LS) mean TATANC was 15.0 hours and 2.8 hours for placebo (P\u00a0&amp;lt; .001). Mavorixafor LS mean TATALC was 15.8 hours and 4.6 hours for placebo (P\u00a0&amp;lt; .001). Annualized infection rates were 60% lower with mavorixafor vs placebo (LS mean 1.7 vs 4.2; nominal P\u00a0= .007), and total infection scores were 40% lower (7.4 [95% confidence interval [CI], 1.6-13.2] vs 12.3 [95% CI, 7.2-17.3]). Treatment with mavorixafor reduced infection frequency, severity, duration, and antibiotic use. No discontinuations occurred due to treatment-emergent adverse events (TEAEs); no related serious TEAEs were observed. Overall, mavorixafor treatment demonstrated significant increases in LS mean TATANC and TATALC, reduced infection frequency, severity\/duration, and was well tolerated. The trial was registered at www.clinicaltrials.gov as #NCT03995108.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023022658","type":"journal-article","created":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T15:54:20Z","timestamp":1713714860000},"page":"35-45","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":63,"title":["A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7375-5410","authenticated-orcid":false,"given":"Raffaele","family":"Badolato","sequence":"first","affiliation":[{"name":"1Department of Clinical and Experimental Sciences, University of Brescia and ASST Spedali Civili, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3559-0018","authenticated-orcid":false,"given":"Laia","family":"Alsina","sequence":"additional","affiliation":[{"name":"2Pediatric Allergy and Clinical Immunology Department, Clinical Immunology and Primary Immunodeficiencies Unit, Hospital Sant Joan de D\u00e9u, Barcelona, Spain"},{"name":"3Department of Surgery and Surgical Specializations, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona, Barcelona, Spain"},{"name":"4Institut de Recerca Sant Joan de D\u00e9u, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Azar","sequence":"additional","affiliation":[{"name":"5Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Bertrand","sequence":"additional","affiliation":[{"name":"6Pediatric Hematology and Oncology Institute, Hospices Civils de Lyon and Claude Bernard University, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5131-1923","authenticated-orcid":false,"given":"Audrey A.","family":"Bolyard","sequence":"additional","affiliation":[{"name":"7University of Washington Medical Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7146-1440","authenticated-orcid":false,"given":"David","family":"Dale","sequence":"additional","affiliation":[{"name":"7University of Washington Medical Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c0ngela","family":"Dey\u00e0-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"2Pediatric Allergy and Clinical Immunology Department, Clinical Immunology and Primary Immunodeficiencies Unit, Hospital Sant Joan de D\u00e9u, Barcelona, Spain"},{"name":"3Department of Surgery and Surgical Specializations, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona, Barcelona, Spain"},{"name":"4Institut de Recerca Sant Joan de D\u00e9u, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Dickerson","sequence":"additional","affiliation":[{"name":"8The University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Ezra","sequence":"additional","affiliation":[{"name":"9California Dermatology Institute, Thousand Oaks, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-9231","authenticated-orcid":false,"given":"Henrik","family":"Hasle","sequence":"additional","affiliation":[{"name":"10Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoung Jin","family":"Kang","sequence":"additional","affiliation":[{"name":"11Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul National University Children\u2019s Hospital, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-4415","authenticated-orcid":false,"given":"Sorena","family":"Kiani-Alikhan","sequence":"additional","affiliation":[{"name":"12Department of Immunology, Royal Free London NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-3370","authenticated-orcid":false,"given":"Taco W.","family":"Kuijpers","sequence":"additional","affiliation":[{"name":"13Department of Pediatric Immunology, Rheumatology and Infectious Disease, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-4136","authenticated-orcid":false,"given":"Alexander","family":"Kulagin","sequence":"additional","affiliation":[{"name":"14RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daman","family":"Langguth","sequence":"additional","affiliation":[{"name":"15Immunology Department, Sullivan Nicolaides Pathology Auchenflower, Wesley Medical Center, Auchenflower, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7774-3529","authenticated-orcid":false,"given":"Carina","family":"Levin","sequence":"additional","affiliation":[{"name":"16Pediatric Hematology Unit, Emek Medical Center, Afula, Israel"},{"name":"17The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Neth","sequence":"additional","affiliation":[{"name":"18Paediatric Infectious Disease, Rheumatology and Immunology Unit, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla, IBiS\/Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Translacional en Infectolog\u00eda Pedi\u00e1trica RITIP, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9853-7903","authenticated-orcid":false,"given":"Peter","family":"Olbrich","sequence":"additional","affiliation":[{"name":"18Paediatric Infectious Disease, Rheumatology and Immunology Unit, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla, IBiS\/Universidad de Sevilla\/CSIC, Red de Investigaci\u00f3n Translacional en Infectolog\u00eda Pedi\u00e1trica RITIP, Seville, Spain"},{"name":"19Departmento de Pediatr\u00eda, Facultad de Medicina, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-5861","authenticated-orcid":false,"given":"Jane","family":"Peake","sequence":"additional","affiliation":[{"name":"20Queensland Children\u2019s Hospital, South Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9857-4456","authenticated-orcid":false,"given":"Yulia","family":"Rodina","sequence":"additional","affiliation":[{"name":"21Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E.","family":"Rutten","sequence":"additional","affiliation":[{"name":"22Department of Hematology, Amsterdam University Medical Centers, Amsterdam, The 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