{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:00:35Z","timestamp":1790190035334,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Health and Labor Sciences Research"},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labor and Welfare of Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["JP21K07847\/JP23K14953)"],"award-info":[{"award-number":["JP21K07847\/JP23K14953)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic active Epstein\u2013Barr virus (EBV) disease (CAEBV) is an uncommon lethal infection involving EBV-infected T cells and\/or natural killer (NK) cells, often complicated by hemophagocytic lymphohistiocytosis (HLH). Patients need curative hematopoietic cell transplantation (HCT), but the indication and timing remain unclear. This study aimed to assess the prognostic value of EBV-infected lymphocyte subsets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 52 pediatric\/young-adult patients diagnosed with persistently EBV infection from 2003 to 2025 at a single tertiary center in Japan, excluding acute infectious mononucleosis and secondary immunodeficiencies. Dominant EBV-infected cell types (CD4+, CD8+, and \u03b3\u03b4 T cells; CD19+ B cells; and CD56+ NK cells) were determined at diagnosis of CAEBV (n = 21), EBV-HLH (n = 19), or inborn errors of immunity (IEI, n = 12). The long-term outcomes were analyzed by major infected cell types and treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CAEBV included 12 T-cell\u2013dominant (6 CD4+, 4 CD8+, and 2 \u03b3\u03b4) and 9 NK-cell\u2013dominant infections. EBV-HLH and IEI exclusively involved CD8+ T-cell and B-cell infections, respectively. Thirteen CAEBV patients (62%) underwent HCT to control progression, including 5 patients who presented with HLH. The 3-year overall survival was 88%, although CD4+ T-cell disease (all CAEBV) showed a significantly lower survival rate. Posttransplant deaths occurred in 3 of 13 CAEBV patients and none of the EBV-HLH patients. Among 9 CAEBV patients with median 11-year progression-free survival without HCT, each one of CD4+ T-cell or NK-cell cases transformed to lymphoma or leukemia after being untreated for &amp;gt;10 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EBV-infected lymphocyte profiling guided prolonged HCT-free control of CAEBV. CD4+ T-cell CAEBV requires a prompt rather than elective HCT to prevent progression and transformation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag191","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:43:48Z","timestamp":1774442628000},"page":"385-395","source":"Crossref","is-referenced-by-count":1,"title":["Long-term Outcomes of Chronic Active Epstein\u2013Barr Virus Infection in Childhood After Dominantly Infected Lymphocyte Subpopulation Management"],"prefix":"10.1093","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2480-8747","authenticated-orcid":false,"given":"Nobutaka","family":"Harada","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]},{"name":"Pediatric Infection and Immunology, Fukuoka Children's Hospital , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0167-3322","authenticated-orcid":false,"given":"Motoshi","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ohga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-7971","authenticated-orcid":false,"given":"Katsuhide","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2916-7889","authenticated-orcid":false,"given":"Shunichi","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishiro","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7519-7336","authenticated-orcid":false,"given":"Yutaro","family":"Yada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-3587","authenticated-orcid":false,"given":"Akira","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Kurume University , Kurume 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