{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:48:13Z","timestamp":1791388093144,"version":"4.3.3"},"reference-count":71,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2020-02783 (FBT)"],"award-info":[{"award-number":["2020-02783 (FBT)"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2023-02193 (AM)"],"award-info":[{"award-number":["2023-02193 (AM)"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Swedish state via the ALF agreement","award":["ALFGBG-718421 (KH)"],"award-info":[{"award-number":["ALFGBG-718421 (KH)"]}]},{"name":"The Swedish state via the ALF agreement","award":["ALFGBG-724881 (AM)"],"award-info":[{"award-number":["ALFGBG-724881 (AM)"]}]},{"name":"The Swedish state via the ALF agreement","award":["ALFGBG-963642 (FBT)"],"award-info":[{"award-number":["ALFGBG-963642 (FBT)"]}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["21 1864 Pj (KH)"],"award-info":[{"award-number":["21 1864 Pj (KH)"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["22 2128 Pj (AM)"],"award-info":[{"award-number":["22 2128 Pj (AM)"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["22 2388 Pj (FBT)"],"award-info":[{"award-number":["22 2388 Pj (FBT)"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Hematology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    Effective strategies to maintain complete remission in adults with acute myeloid leukemia (AML) are critically needed. Early clinical trials aimed at preventing relapse in the postconsolidation phase explored prolonged chemotherapy, single-agent immunotherapy, and hybrid chemo-immunotherapy, but none of these approaches produced practice-changing results. More recent trials have identified efficacious remission maintenance strategies, including (1) midostaurin or quizartinib for patients with\n                    <jats:italic toggle=\"yes\">FLT3<\/jats:italic>\n                    -mutated AML, (2) oral azacitidine for older AML patients, and (3) immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC\/IL-2) for younger patients. In this review, we examine key phase III trial and follow-up study results for approved remission maintenance therapies, with a particular focus on HDC\/IL-2. We discuss clinical efficacy in relation to patient age and anti-leukemic immunity as well as leukemic cell chemosensitivity, chromosomal integrity, and mutational profiles. Finally, we propose a role for HDC\/IL-2 within an evolving landscape of strategies to achieve durable remission in a broader population of AML patients.\n                  <\/jats:p>","DOI":"10.1177\/20406207251351086","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T05:51:38Z","timestamp":1751089898000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Histamine dihydrochloride and low-dose interleukin-2 in an emerging landscape of relapse prevention in acute myeloid leukemia"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-2617","authenticated-orcid":false,"given":"Malin S.","family":"Nilsson","sequence":"first","affiliation":[{"name":"TIMM Laboratory, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-5221","authenticated-orcid":false,"given":"Anna","family":"Martner","sequence":"additional","affiliation":[{"name":"TIMM Laboratory, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovisa","family":"Wennstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hansson","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik B.","family":"Thor\u00e9n","sequence":"additional","affiliation":[{"name":"TIMM Laboratory, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer","family":"Hellstrand","sequence":"additional","affiliation":[{"name":"TIMM Laboratory, Sahlgrenska Center for Cancer Research, University of Gothenburg, Box 425, 40530 Gothenburg, Sweden"},{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100873"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280798"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.240754"},{"key":"e_1_3_4_6_2","unstructured":"Cancer.Net. Leukemia\u2014acute myeloid\u2014AML: Statistics https:\/\/www.cancer.net\/cancer-types\/leukemia-acute-myeloid-aml\/statistics (2023 accessed 18 August 2023)."},{"key":"e_1_3_4_7_2","unstructured":"Cancer Research UK. Survival for acute myeloid leukaemia (AML) https:\/\/www.cancerresearchuk.org\/about-cancer\/acute-myeloid-leukaemia-aml\/survival (2022 accessed 18 September 2023)."},{"key":"e_1_3_4_8_2","first-page":"124","article-title":"Outcomes of patients with relapsed or refractory acute myeloid leukemia: a population-based real-world study","volume":"10","author":"Brandwein JM","year":"2020","unstructured":"Brandwein JM, Saini L, Geddes MN, et al. Outcomes of patients with relapsed or refractory acute myeloid leukemia: a population-based real-world study. Am J Blood Res 2020; 10: 124\u2013133.","journal-title":"Am J Blood Res"},{"key":"e_1_3_4_9_2","first-page":"2289","article-title":"Maintenance therapy in acute myeloid leukemia: advances and controversies","volume":"108","author":"Senapati J","year":"2023","unstructured":"Senapati J, Kadia TM, Ravandi F. Maintenance therapy in acute myeloid leukemia: advances and controversies. Haematologica 2023; 108: 2289\u20132304.","journal-title":"Haematologica"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614359"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00464-6"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2004444"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100829"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4073"},{"key":"e_1_3_4_15_2","unstructured":"European Medicines Agency. Ceplene https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/ceplene (2018 accessed 24 June 2025)."},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2013.06.006"},{"key":"e_1_3_4_17_2","article-title":"Role of natural killer cell subsets and natural cytotoxicity receptors for the outcome of immunotherapy in acute myeloid leukemia","volume":"5","author":"Martner A","year":"2015","unstructured":"Martner A, Rydstr\u00f6m A, Riise RE, et al. Role of natural killer cell subsets and natural cytotoxicity receptors for the outcome of immunotherapy in acute myeloid leukemia. Oncoimmunology 2015; 5: e1041701.","journal-title":"Oncoimmunology"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7210"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1636598"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16320"},{"key":"e_1_3_4_21_2","first-page":"3781","article-title":"Histamine dihydrochloride and low-dose interleukin-2 has anti-leukemic efficacy in NPM1-mutated and myelomonocytic\/monocytic acute myeloid leukemia","volume":"109","author":"Nilsson MS","year":"2024","unstructured":"Nilsson MS, Fiegl M, Hiddemann W, et al. Histamine dihydrochloride and low-dose interleukin-2 has anti-leukemic efficacy in NPM1-mutated and myelomonocytic\/monocytic acute myeloid leukemia. Haematologica 2024; 109: 3781\u20133784.","journal-title":"Haematologica"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100905"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01179-4"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.02.018"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007223"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001920"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016293"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-10-879866"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-337725"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-466706"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1702411"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-157326"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2018.12.001"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.05.002"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100654"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101073"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2022.100991"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-01980-3"},{"key":"e_1_3_4_39_2","first-page":"724","article-title":"In vitro susceptibility of acute leukemia cells to the cytotoxic activity of allogeneic and autologous lymphokine activated killer (LAK) effectors: correlation with the rate and duration of complete remission and with survival","volume":"8","author":"Lauria F","year":"1994","unstructured":"Lauria F, Raspadori D, Rondelli D, et al. In vitro susceptibility of acute leukemia cells to the cytotoxic activity of allogeneic and autologous lymphokine activated killer (LAK) effectors: correlation with the rate and duration of complete remission and with survival. Leukemia 1994; 8: 724\u2013728.","journal-title":"Leukemia"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00218"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-391722"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999099313073"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.066399"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.11.4940"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1996.d01-291.x"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1053\/sonc.2002.33081"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1996.tb01383.x"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0382"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0528-1"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.00389.x"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6215-12-86"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.039131"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-009-0642-1"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V110.11.4381.4381"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.3109\/07357907.2011.568563"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5559"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.5VMA1116-455R"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-2040-9"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1599110"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2253-6"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2021.1944538"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.151"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0711"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-874990"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.796072"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0274-y"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa074306"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-2164"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2024.2444466"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2248"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.252"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100863"}],"container-title":["Therapeutic Advances in Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207251351086","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20406207251351086","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207251351086","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:17:49Z","timestamp":1777591069000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20406207251351086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":71,"alternative-id":["10.1177\/20406207251351086"],"URL":"https:\/\/doi.org\/10.1177\/20406207251351086","relation":{},"ISSN":["2040-6207","2040-6215"],"issn-type":[{"value":"2040-6207","type":"print"},{"value":"2040-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,28]]},"article-number":"20406207251351086"}}