{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T11:59:02Z","timestamp":1766404742279,"version":"3.48.0"},"reference-count":54,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting\u2014when MRD is not detectable. However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its wide application. To address this challenge, several alternative cell-based strategies have been developed. One of these is represented by cytokine-induced killer (CIK) cells, generated from donor peripheral blood mononuclear cells through stimulation with anti-CD3 antibodies, interferon-\u03b3, and interleukin-2. These cells are characterized by a hybrid phenotype, combining T-cell functions with natural killer-like properties, and exhibit antitumor activity in an MHC-unrestricted manner. CIK cells are generally well tolerated and associated with low toxicity but their efficacy is so far modest. Based on the experience of CAR-T in the treatment of B-cell lymphoid disease, CIK cells have been engineered with chimeric antigen receptors (CAR) developing the CARCIK cells. This novel cellular strategy represents a promising approach in the treatment of acute myeloid and lymphoid leukemia relapsed post-allo-HSCT. This review provides an overview of the current CAR-CIK experiences in the setting of acute leukemias and outlines future directions for their clinical translation.<\/jats:p>","DOI":"10.3390\/cancers18010032","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T11:43:31Z","timestamp":1766403811000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of CAR-CIK Cells in Acute Leukemia Relapsed Post Allogeneic Stem Cell Transplantation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4703-6280","authenticated-orcid":false,"given":"Martina","family":"Canichella","sequence":"first","affiliation":[{"name":"Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"de Fabritiis","sequence":"additional","affiliation":[{"name":"Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy"},{"name":"Department of Biomedicina e Prevenzione, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-6491","authenticated-orcid":false,"given":"Elisabetta","family":"Abruzzese","sequence":"additional","affiliation":[{"name":"Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy"},{"name":"Department of Biomedicina e Prevenzione, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1182\/blood-2006-05-018192","article-title":"Outcome of 609 Adults After Relapse of Acute Lymphoblastic Leukemia (ALL)","volume":"109","author":"Fielding","year":"2007","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"808","DOI":"10.3324\/haematol.2009.014274","article-title":"Outcome after relapse of acute lymphoblastic leukemia in adult patients","volume":"95","author":"Oriol","year":"2010","journal-title":"Haematologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/bmt.2012.195","article-title":"Outcomes of second allogeneic hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia","volume":"48","author":"Poon","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_4","first-page":"3543","article-title":"Outcomes and genetic dynamics of acute myeloid leukemia at first relapse","volume":"109","author":"Bataller","year":"2024","journal-title":"Haematologica"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.bbmt.2014.11.007","article-title":"Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: A Center for International Blood and Marrow Transplant Research study","volume":"21","author":"Bejanyan","year":"2015","journal-title":"Biol. 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