{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:01:20Z","timestamp":1761897680094,"version":"build-2065373602"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Funds via Foundation for Science and Technology (FCT)","award":["UID\/NEU\/04539\/2019","UIDB\/04539\/2020","UIDP\/04539\/2020"],"award-info":[{"award-number":["UID\/NEU\/04539\/2019","UIDB\/04539\/2020","UIDP\/04539\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Onco"],"abstract":"<jats:p>Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy. We aimed to study ICI as monotherapy and\/or combined therapy (with chemotherapy (QT), for AML patients. The PRISMA statement was used. The literature used comprised clinical trials, randomized controlled trials, and systematic reviews published within the last 7 years. The blockade of CTLA-4 presented a 42% of complete remission within AML. Nivolumab in high-risk AML showed a median recurrence-free survival (RFS) of 8.48 months. The same drug on relapsed hematologic malignancies after allogenic transplantation shows a 1-year OS of 56%. The use of prophylaxis post allogenic transplantation cyclophosphamide (PTCy), following checkpoint inhibition, demonstrated different baseline disease and transplantation characteristics when compared to no-PCTy patients, being 32% and 10%, respectively. CTLA-4 blockage was a worthy therapeutic approach in relapsed hematologic malignancies, presenting long-lasting responses. The approach to AML and myelodysplastic syndrome patients with ICI before allogenic hematopoietic stem cell transplantation and the use of a graft-versus-host disease prophylaxis have shown improvement in the transplantation outcomes, and therefore AML treatment.<\/jats:p>","DOI":"10.3390\/onco2030011","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T03:50:36Z","timestamp":1657597836000},"page":"164-180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"2","author":[{"given":"Margarida","family":"Silva","sequence":"first","affiliation":[{"name":"Polytechnic of Coimbra, ESTESC, UCPCBL, Rua 5 de Outubro, SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1457-8992","authenticated-orcid":false,"given":"Diana","family":"Martins","sequence":"additional","affiliation":[{"name":"Polytechnic of Coimbra, ESTESC, UCPCBL, Rua 5 de Outubro, SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"},{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Ci\u00eancias Aplicadas \u00e0 Sa\u00fade (LabinSa\u00fade), Polit\u00e9cnico de Coimbra, ESTESC, Rua 5 de Outubro\u2013SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"},{"name":"Biophysics Institute of Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5205-8939","authenticated-orcid":false,"given":"Fernando","family":"Mendes","sequence":"additional","affiliation":[{"name":"Polytechnic of Coimbra, ESTESC, UCPCBL, Rua 5 de Outubro, SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"},{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Ci\u00eancias Aplicadas \u00e0 Sa\u00fade (LabinSa\u00fade), Polit\u00e9cnico de Coimbra, ESTESC, Rua 5 de Outubro\u2013SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"},{"name":"Biophysics Institute of Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"},{"name":"European Association for Professions in Biomedical Sciences, B-1000 Brussels, Belgium"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"882531","DOI":"10.3389\/fonc.2022.882531","article-title":"Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: A Meta-Analysis","volume":"12","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_2","first-page":"38","article-title":"Acute Myeloid Leukemia: A Review","volume":"103","author":"Pelcovits","year":"2020","journal-title":"Rhode Isl. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/ijc.31937","article-title":"Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods","volume":"144","author":"Ferlay","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_4","first-page":"1","article-title":"Clinical and epidemiological aspects of leukemias Aspectos cl\u00ednicos y epidemiol\u00f3gicos de las leucemias","volume":"33","author":"Almeida","year":"2017","journal-title":"Rev. Cuba. Hematol. Inmunol. Hemoter."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.blre.2019.04.005","article-title":"Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges","volume":"36","author":"Shallis","year":"2019","journal-title":"Blood Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41392-020-00361-x","article-title":"Targeting multiple signaling pathways: The new approach to acute myeloid leukemia therapy","volume":"5","author":"Carter","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103607","DOI":"10.1016\/j.critrevonc.2022.103607","article-title":"Diagnosis and treatment of therapy-related acute myeloid leukemia","volume":"171","author":"Strickland","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1038\/bcj.2016.50","article-title":"Acute myeloid leukemia: A comprehensive review and 2016 update","volume":"6","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/ijlh.13135","article-title":"How I investigate acute myeloid leukemia","volume":"42","author":"Narayanan","year":"2020","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_10","first-page":"2391","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood Am. Soc. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"n2026","DOI":"10.1136\/bmj.n2026","article-title":"Advances in acute myeloid leukemia","volume":"375","author":"Newell","year":"2021","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.biopha.2017.10.100","article-title":"Immunotherapy for acute myeloid leukemia (AML): A potent alternative therapy","volume":"97","author":"Acheampong","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"963","DOI":"10.2217\/fon-2017-0459","article-title":"Advances in immunotherapy for acute myeloid leukemia","volume":"14","author":"Przespolewski","year":"2018","journal-title":"Futur. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5502","DOI":"10.1158\/1078-0432.CCR-17-3016","article-title":"Novel approaches to acute myeloid leukemia immunotherapy","volume":"24","author":"Gill","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"612880","DOI":"10.3389\/fonc.2020.612880","article-title":"FLT3 Mutations in Acute Myeloid Leukemia: Key Concepts and Emerging Controversies","volume":"10","author":"Kennedy","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"610820","DOI":"10.3389\/fonc.2020.610820","article-title":"TP53 Mutations in Acute Myeloid Leukemia: Still a Daunting Challenge?","volume":"10","author":"Molica","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.2147\/DDDT.S89114","article-title":"Receptor tyrosine kinase (c-Kit) inhibitors: A potential therapeutic target in cancer cells","volume":"10","author":"Babaei","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1182\/blood.2019004226","article-title":"NPM1-mutated acute myeloid leukemia: From bench to bedside","volume":"15","author":"Falini","year":"2020","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"806137","DOI":"10.3389\/fonc.2022.806137","article-title":"Acute Myeloid Leukemia With CEBPA Mutations: Current Progress and Future Directions","volume":"12","author":"Su","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_20","first-page":"1","article-title":"Acute myeloid leukemia in the older adults","volume":"6","author":"Almeida","year":"2016","journal-title":"Leuk. Res. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/bmt.2016.274","article-title":"PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation","volume":"52","author":"Albring","year":"2017","journal-title":"Bone Marrow Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1101\/gad.349368.122","article-title":"Translating recent advances in the pathogenesis of acute myeloid leukemia to the clinic","volume":"34","author":"Bewersdorf","year":"2022","journal-title":"Genes Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00005-019-00566-1","article-title":"HER2-Positive Breast Cancer Immunotherapy: A Focus on Vaccine Development","volume":"68","author":"Arab","year":"2020","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Henriques, B., Mendes, F., and Martins, D. (2021). Immunotherapy in Breast Cancer: When, How, and What Challenges?. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111687"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1056\/NEJMoa1809615","article-title":"Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer","volume":"379","author":"Schmid","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.acuro.2020.01.009","article-title":"Prostate cancer, new treatment advances\u2014Immunotherapy","volume":"44","author":"Silva","year":"2020","journal-title":"Actas Urol\u00f3gicas Espa\u00f1olas"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1007\/s00345-018-2332-5","article-title":"Development of immunotherapy in bladder cancer: Present and future on targeting PD(L)1 and CTLA-4 pathways","volume":"36","author":"Rouanne","year":"2018","journal-title":"World J. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1001\/jamaoncol.2017.5440","article-title":"Atezolizumab (MPDL3280A) monotherapy for patients with metastatic urothelial cancer long-term outcomes from a phase 1 study","volume":"4","author":"Petrylak","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2147\/DDDT.S141491","article-title":"Durvalumab: An investigational anti-pd-l1 monoclonal antibody for the treatment of urothelial carcinoma","volume":"12","author":"Faiena","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1590\/s1677-5538.ibju.2020.0681","article-title":"The role of immunotherapy in advanced renal cell carcinoma: Review","volume":"47","author":"Mondlane","year":"2021","journal-title":"Int. Braz. J. Urol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1056\/NEJMoa1816714","article-title":"Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma","volume":"380","author":"Rini","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.3324\/haematol.2016.143180","article-title":"Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a growth factor independence 1 dependent manner","volume":"101","author":"Botezatu","year":"2016","journal-title":"Haematologica"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1080\/10428194.2017.1344905","article-title":"The emerging role of immune checkpoint based approaches in AML and MDS","volume":"59","author":"Boddu","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/bfgp\/ely027","article-title":"Immune checkpoints and cancer in the immunogenomics era","volume":"18","author":"Park","year":"2019","journal-title":"Brief. Funct. Genom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.bbcan.2016.02.002","article-title":"The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation","volume":"1865","author":"Mendes","year":"2016","journal-title":"Biochim. Biophys. Acta-Rev. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fimmu.2022.811144","article-title":"Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches","volume":"13","author":"Menter","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/0145-2126(91)90033-P","article-title":"Cellular cytotoxic function and potential in acute myelogenous leukaemia","volume":"15","author":"Lim","year":"1991","journal-title":"Leuk. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1182\/blood-2009-02-206946","article-title":"Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts","volume":"114","author":"Taussig","year":"2009","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fimmu.2012.00051","article-title":"Molecular mechanisms of treg-mediated T cell suppression","volume":"3","author":"Schmidt","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/10245332.2015.1106814","article-title":"Indoleamine 2,3-dioxygenase and regulatory T cells in acute myeloid leukemia","volume":"21","author":"Mansour","year":"2016","journal-title":"Hematology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3389\/fonc.2021.632623","article-title":"Reactive Oxygen Species Rewires Metabolic Activity in Acute Myeloid Leukemia","volume":"11","author":"Robinson","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1182\/blood-2009-03-206672","article-title":"PD-1\/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model","volume":"114","author":"Zhang","year":"2009","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.3389\/fonc.2021.753677","article-title":"TIM-3 in Leukemia; Immune Response and Beyond","volume":"11","author":"Rezaei","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"294","DOI":"10.5045\/br.2018.53.4.294","article-title":"Overexpression of indoleamine 2,3-dioxygenase correlates with regulatory T cell phenotype in acute myeloid leukemia patients with normal karyotype","volume":"53","author":"Arandi","year":"2018","journal-title":"Blood Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.3389\/fimmu.2018.02227","article-title":"Acute Myeloid Leukemia Cells Express ICOS Ligand to Promote the Expansion of Regulatory T Cells","volume":"9","author":"Han","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41375-021-01350-x","article-title":"Catch me if you can: How AML and its niche escape immunotherapy","volume":"36","author":"Tettamanti","year":"2022","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1182\/blood-2013-01-480129","article-title":"Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment","volume":"122","author":"Mussai","year":"2013","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1111\/cas.13827","article-title":"Reinforce the antitumor activity of CD8+ T cells via glutamine restriction","volume":"109","author":"Nabe","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"919","DOI":"10.3389\/fonc.2021.584884","article-title":"Tumor Microenvironmental Competitive Endogenous RNA Network and Immune Cells Act as Robust Prognostic Predictor of Acute Myeloid Leukemia","volume":"11","author":"Cheng","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41586-019-1410-1","article-title":"Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion","volume":"572","author":"Paczulla","year":"2019","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/gene.2014.58","article-title":"Methylation of NKG2D ligands contributes to immune system evasion in acute myeloid leukemia","volume":"16","author":"Fernandez","year":"2015","journal-title":"Genes Immun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13045-017-0486-z","article-title":"Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia","volume":"10","author":"Zhu","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1158\/1078-0432.CCR-15-2626","article-title":"T-cell immunoglobulin and ITIM domain (TIGIT) associates with CD8+ T-cell exhaustion and poor clinical outcome in AML patients","volume":"22","author":"Kong","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1471-4906(02)02302-5","article-title":"Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes","volume":"23","author":"Mantovani","year":"2002","journal-title":"Trends Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3389\/fimmu.2020.01371","article-title":"Myeloid-Derived Suppressor Cells in Tumors: From Mechanisms to Antigen Specificity and Microenvironmental Regulation","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1062208","DOI":"10.1080\/2162402X.2015.1062208","article-title":"Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome","volume":"5","author":"Kittang","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1056\/NEJMoa1808777","article-title":"Immune Escape of Relapsed AML Cells after Allogeneic Transplantation","volume":"379","author":"Christopher","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11912-019-0781-7","article-title":"Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets","volume":"21","author":"Stahl","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1002\/sctm.20-0147","article-title":"Cell-based and antibody-mediated immunotherapies directed against leukemic stem cells in acute myeloid leukemia: Perspectives and open issues","volume":"9","author":"Valent","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11864-020-00765-5","article-title":"Treatment of Relapsed Acute Myeloid Leukemia","volume":"21","author":"Thol","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-3-319-67577-0_5","article-title":"Immunogenic and non-immunogenic cell death in the tumor microenvironment","volume":"1036","author":"Pitt","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.canlet.2018.01.050","article-title":"Immunogenic chemotherapy: Dose and schedule dependence and combination with immunotherapy","volume":"419","author":"Wu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/bjh.16185","article-title":"Graft-versus-host disease and graft-versus-leukaemia effects in secondary acute myeloid leukaemia: A retrospective, multicentre registry analysis from the Acute Leukaemia Working Party of the EBMT","volume":"188","author":"Baron","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/bjh.16355","article-title":"The role of allogeneic stem cell transplantation in the management of acute myeloid leukaemia: A triumph of hope and experience","volume":"188","author":"Loke","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1182\/blood-2017-01-761346","article-title":"PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: High response rate but frequent GVHD","volume":"130","author":"Haverkos","year":"2017","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.3389\/fonc.2019.01217","article-title":"The Graft-Versus-Leukemia Effect in AML","volume":"9","author":"Sweeney","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13046-021-01987-7","article-title":"Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer","volume":"40","author":"Zhang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/ijc.33415","article-title":"Targeting CTLA-4 in cancer: Is it the ideal companion for PD-1 blockade immunotherapy combinations?","volume":"149","author":"Aiello","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13045-017-0474-3","article-title":"Checkpoint inhibitors in hematological malignancies","volume":"10","author":"Ok","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Giannopoulos, K. (2019). Targeting Immune Signaling Checkpoints in Acute Myeloid Leukemia. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020236"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jimbu, L., Mesaros, O., Popescu, C., Neaga, A., Berceanu, I., Dima, D., Gaman, M., and Zdrenghea, M. (2021). Is there a place for PD-1-PD-L blockade in acute myeloid leukemia?. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040288"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1056\/NEJMoa1601202","article-title":"Ipilimumab for Patients with Relapse after Allogeneic Transplantation","volume":"375","author":"Davids","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1172\/JCI129204","article-title":"Immune escape and immunotherapy of acute myeloid leukemia","volume":"130","author":"Vago","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41408-021-00453-z","article-title":"Nivolumab maintenance in high-risk acute myeloid leukemia patients: A single-arm, open-label, phase II study","volume":"11","author":"Reville","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1182\/blood.2019004710","article-title":"A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation","volume":"135","author":"Davids","year":"2020","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/ajh.25750","article-title":"Harnessing the immune system after allogeneic stem cell transplant in acute myeloid leukemia","volume":"95","author":"Sterling","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e480","DOI":"10.1016\/S2352-3026(19)30114-0","article-title":"Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: A single-arm, phase 2 study","volume":"6","author":"Ravandi","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1002\/cncr.32796","article-title":"Posttransplantation cyclophosphamide improves transplantation outcomes in patients with AML\/MDS who are treated with checkpoint inhibitors","volume":"126","author":"Oran","year":"2020","journal-title":"Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3389\/fphar.2019.00609","article-title":"A review of efficacy and safety of checkpoint inhibitor for the treatment of acute myeloid leukemia","volume":"10","author":"Liao","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Davidson-Moncada, J., Viboch, E., Church, S.E., Warren, S.E., and Rutella, S. (2018). Dissecting the immune landscape of acute myeloid leukemia. Biomedicines, 6.","DOI":"10.3390\/biomedicines6040110"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"656218","DOI":"10.3389\/fonc.2021.656218","article-title":"Immunotherapy in Acute Myeloid Leukemia: Where We Stand","volume":"11","author":"Isidori","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/14737140.2019.1589374","article-title":"Immune checkpoint-based therapy in myeloid malignancies: A promise yet to be fulfilled","volume":"19","author":"Bewersdorf","year":"2019","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"634435","DOI":"10.3389\/fimmu.2021.634435","article-title":"The Role of Immune Checkpoint Molecules for Relapse After Allogeneic Hematopoietic Cell Transplantation","volume":"12","author":"Ruess","year":"2021","journal-title":"Front. 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