{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T22:13:16Z","timestamp":1778105596487,"version":"3.51.4"},"reference-count":54,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"14","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,5,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Patients with high-risk (HR) leukemia remain at substantial risk of early relapse, treatment-related toxicity, and poor survival, underscoring the need for effective relapse prevention therapies. To our knowledge, this first-in-human, disease burden\u2013guided study evaluated the feasibility, safety, and efficacy of donor-derived allogeneic interleukin-15\u2013activated cytokine-induced killer cells (IL15-CIK) combining T-cell and natural killer cell properties for post-transplant disease control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In a prospective, multicenter phase I\/II trial (EudraCT 2013-005446-11) and an identically designed pilot study, 53 adult and pediatric patients with HR leukemia received 56 courses of IL15-CIK monotherapy after human leukocyte antigen (HLA)\u2013matched or HLA-mismatched transplantation. Treatment intent was categorized as consolidation (13%), preemptive (61%), or salvage (27%) with 169 infusions administered as a single dose (29%) or according to adaptable dose-escalation regimens (71%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Acute graft-versus-host disease (GVHD) grades 1-2 and grade 3 occurred in 27% and 4% of cases, respectively; no extensive chronic GVHD or treatment-related mortality was observed. IL15-CIK\u2013associated adverse events were predominantly mild. Disease clearance, assessed by the cumulative incidence of complete molecular remission, peaked at day 700, reaching 74% in the preemptive and 13% in the salvage setting. The five-year progression-free survival was 50% overall and highest (69%) in pediatric acute myeloid leukemia. The five-year overall survival (OS) was 71% in the consolidation, 61% in the preemptive, and 20% in the salvage setting. Multivariable analysis demonstrated significantly lower relapse rates with Campath compared with ATG, superior OS in myeloid malignancies, and reduced IL15-CIK efficacy in advanced disease. The median follow-up was 7.3 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>IL15-CIK monotherapy is feasible and safe and demonstrates promising relapse-preventive activity after hematopoietic stem-cell transplantation. Clinical outcomes are strongly influenced by disease burden at treatment initiation and previous serotherapy, supporting optimized patient selection and timing in future post-transplant immunotherapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01966","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T20:00:08Z","timestamp":1775505608000},"page":"1323-1336","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["First-in-Human Study of IL15\u2013Activated Cytokine-Induced Killer Cells After Allogeneic HCT Shows Durable Remission and Serotherapy-Associated Immune Reconstitution in Leukemia"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7178-3147","authenticated-orcid":true,"given":"Eva","family":"Rettinger","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4047-975X","authenticated-orcid":true,"given":"Dirk","family":"Heckl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"},{"name":"Institute for Experimental Pediatric Hematology and Oncology (EPHO), Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7455-8037","authenticated-orcid":true,"given":"Martin","family":"Hutter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Salzmann-Manrique","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Luedtke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Huenecke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Bremm","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Cappel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2359-131X","authenticated-orcid":true,"given":"Gesine","family":"Bug","sequence":"additional","affiliation":[{"name":"Medical Clinical II, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1821-1183","authenticated-orcid":true,"given":"Johann","family":"Greil","sequence":"additional","affiliation":[{"name":"University Children's Hospital, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5230-0628","authenticated-orcid":true,"given":"Roland","family":"Meisel","sequence":"additional","affiliation":[{"name":"Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0728-2253","authenticated-orcid":true,"given":"Eva Maria","family":"Wagner-Drouet","sequence":"additional","affiliation":[{"name":"Johannes Gutenberg-University Mainz, III. 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