{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:41:18Z","timestamp":1788536478028,"version":"build-2803163510"},"reference-count":80,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The development of a second malignancy after the diagnosis of childhood acute lymphoblastic leukemia (ALL) is a rare event. Certain second malignancies have been linked with specific elements of leukemia therapy, yet the etiology of most second neoplasms remains obscure and their optimal management strategies are unclear. This is a first comprehensive report of non-Hodgkin lymphomas (NHLs) following pediatric ALL therapy, excluding stem-cell transplantation. We analyzed data of patients who developed NHL following ALL diagnosis and were enrolled in 12 collaborative pediatric ALL trials between 1980-2018. Eighty-five patients developed NHL, with mature B-cell lymphoproliferations as the dominant subtype (56 of 85 cases). Forty-six of these 56 cases (82%) occurred during or within 6 months of maintenance therapy. The majority exhibited histopathological characteristics associated with immunodeficiency (65%), predominantly evidence of Epstein-Barr virus\u2013driven lymphoproliferation. We investigated 66 cases of post-ALL immunodeficiency-associated lymphoid neoplasms, 52 from our study and 14 additional cases from a literature search. With a median follow-up of 4.9 years, the 5-year overall survival for the 66 patients with immunodeficiency-associated lymphoid neoplasms was 67.4% (95% confidence interval [CI], 56-81). Five-year cumulative risks of lymphoid neoplasm\u2013 and leukemia-related mortality were 20% (95% CI, 10.2-30) and 12.4% (95% CI, 2.7-22), respectively. Concurrent hemophagocytic lymphohistiocytosis was associated with increased mortality (hazard ratio, 7.32; 95% CI, 1.62-32.98; P\u00a0=\u00a0.01). A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.<\/jats:p>","DOI":"10.1182\/blood.2022016975","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T15:57:43Z","timestamp":1667577463000},"page":"743-755","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":7,"title":["EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-7578","authenticated-orcid":false,"given":"Sarah","family":"Elitzur","sequence":"first","affiliation":[{"name":"1Department of Pediatric Hematology and Oncology, Schneider Children\u2019s Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Vora","sequence":"additional","affiliation":[{"name":"2Department of Paediatric Haematology, Great Ormond Street Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-829X","authenticated-orcid":false,"given":"Birgit","family":"Burkhardt","sequence":"additional","affiliation":[{"name":"3Pediatric Hematology and Oncology, University Hospital M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Inaba","sequence":"additional","affiliation":[{"name":"4Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andishe","family":"Attarbaschi","sequence":"additional","affiliation":[{"name":"5Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Baruchel","sequence":"additional","affiliation":[{"name":"6Department of Pediatric Hematology, H\u00f4pital Robert Debr\u00e9, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Escherich","sequence":"additional","affiliation":[{"name":"7Department of Pediatric Hematology and Oncoogy, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Gibson","sequence":"additional","affiliation":[{"name":"8Department of Paediatric Haematology, Royal Hospital for Children, Glasgow, United 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United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"M\u00f6ricke","sequence":"additional","affiliation":[{"name":"12Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Pieters","sequence":"additional","affiliation":[{"name":"13Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-424X","authenticated-orcid":false,"given":"Anne","family":"Uyttebroeck","sequence":"additional","affiliation":[{"name":"14Department of Paediatric Haematology and Oncology, University Hospital Leuven, Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Baird","sequence":"additional","affiliation":[{"name":"15Department of Haematology, Royal 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