Effective Immunosurveillance After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia

References

• PasswegJR, BaldomeroH, BaderP, et al.; for the European Society for Blood and Marrow Transplantation (EBMT). Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. Bone Marrow Transplant. 2016;51(6):786–792. doi:10.1038/bmt.2016.20.26901709
   PubMed Web of Science ®Google Scholar
• CornelissenJJ, GratwohlA, SchlenkRF, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012;9(10):579–590. doi:10.1038/nrclinonc.2012.15022949046
   PubMed Web of Science ®Google Scholar
• KorethJ, SchlenkR, KopeckyKJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301(22):2349–2361. doi:10.1001/jama.2009.81319509382
   PubMed Web of Science ®Google Scholar
• PasswegJR, BaldomeroH, BaderP, et al.; for the European Society for Blood and Marrow Transplantation (EBMT). Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant. 2018;53(9):1139–1148. doi:10.1038/s41409-018-0153-1.29540849
   PubMed Web of Science ®Google Scholar
• DuarteRF, LabopinM, BaderP, et al.; for the European Society for Blood and Marrow Transplantation (EBMT). Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant. 2019;54(10):1525–1552. doi:10.1038/s41409-019-0516-2.30953028
   PubMed Web of Science ®Google Scholar
• DöhnerH, EsteyE, GrimwadeD, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447. doi:10.1182/blood-2016-08-73319627895058
   PubMed Web of Science ®Google Scholar
• StölzelF, PlatzbeckerU, MohrB, et al. Early intervention with allogeneic hematopoietic cell transplantation during chemotherapy-induced aplasia in patients with high-risk acute myeloid leukemia. Leukemia. 2013;27(10):2068–2072. doi:10.1038/leu.2013.14223648670
   PubMed Web of Science ®Google Scholar
• MiddekeJM, HerbstR, ParmentierS, et al.; for the Study Alliance Leukemia (SAL). Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016;30(2):261–267. doi:10.1038/leu.2015.226.26283567
   PubMed Web of Science ®Google Scholar
• de LimaM, PorterDL, BattiwallaM, et al. Proceedings from the National Cancer Institute’s Second International Workshop on the biology, prevention, and treatment of relapse after hematopoietic stem cell transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transplant. 2014;20(1):4–13. doi:10.1016/j.bbmt.2013.08.01224018392
   PubMed Web of Science ®Google Scholar
• HorowitzM, SchreiberH, ElderA, et al. Epidemiology and biology of relapse after stem cell transplantation. Bone Marrow Transplant. 2018;53(11):1379–1389. doi:10.1038/s41409-018-0171-z29670211
   PubMed Web of Science ®Google Scholar
• BejanyanN, WeisdorfDJ, LoganBR, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transplant. 2015;21(3):454–459. doi:10.1016/j.bbmt.2014.11.00725460355
   PubMed Web of Science ®Google Scholar
• SchmidC, LabopinM, NaglerA, et al. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood. 2012;119(6):1599–1606. doi:10.1182/blood-2011-08-37584022167752
   PubMed Web of Science ®Google Scholar
• SchmidC, LabopinM, NaglerA, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT acute leukemia working party. J Clin Oncol. 2007;25(31):4938–4945. doi:10.1200/JCO.2007.11.605317909197
   PubMed Web of Science ®Google Scholar
• ChristopeitM, KussO, FinkeJ, et al. Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. J Clin Oncol. 2013;31(26):3259–3271. doi:10.1200/JCO.2012.44.796123918951
   PubMed Web of Science ®Google Scholar
• LeeCJ, SavaniBN, MohtyM, et al. Post-remission strategies for the prevention of relapse following allogeneic hematopoietic cell transplantation for high-risk acute myeloid leukemia: expert review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2019;54(4):519–530. doi:10.1038/s41409-018-0286-230104717
   PubMed Web of Science ®Google Scholar
• RautenbergC, GermingU, HaasR, KobbeG, SchroederT. Relapse of acute myeloid leukemia after allogeneic stem cell transplantation: prevention, detection, and treatment. Int J Mol Sci. 2019;20(1):228. doi:10.3390/ijms20010228
   PubMed Web of Science ®Google Scholar
• HorowitzMM, GaleR, SondelPM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–562. doi:10.1182/blood.V75.3.555.bloodjournal7535552297567
   PubMed Web of Science ®Google Scholar
• WeidenPL, SullivanKM, FlournoyN, StorbR, ThomasED. Antileukemic effect of chronic graft-versus-host disease. N Engl J Med. 1981;304(25):1529–1533. doi:10.1056/NEJM1981061830425077015133
   PubMed Web of Science ®Google Scholar
• ButturiniA, BortinM, GaleR. Graft-versus-leukemia following bone marrow transplantation. Bone Marrow Transplant. 1987;2(3):233–242.3332173
   PubMed Web of Science ®Google Scholar
• BornhäuserM, KienastJ, TrenschelR, et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012;13(10):1035–1044. doi:10.1016/S1470-2045(12)70349-222959335
   PubMed Web of Science ®Google Scholar
• BeelenDW, TrenschelR, StelljesM, et al. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 2020;7(1):e28–e39. doi:10.1016/S2352-3026(19)30157-731606445
   PubMed Web of Science ®Google Scholar
• RingdénO, BoumendilA, LabopinM, et al. Outcome of allogeneic hematopoietic stem cell transplantation in patients age >69 years with acute myelogenous leukemia: on behalf of the acute leukemia working party of the European society for blood and marrow transplantation. Biol Blood Marrow Transplant. 2019;25(10):1975–1983. doi:10.1016/j.bbmt.2019.05.03731181255
   PubMed Web of Science ®Google Scholar
• LiJ-M, GiverCR, LuY, HossainMS, AkhtariM, WallerK. Separating graft-versus-leukemia from graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Immunotherapy. 2010;34:599–621.
   Google Scholar
• WarrenEH, DeegHJ. Dissecting graft-versus-leukemia from graft-versus-host-disease using novel strategies: dissecting GVL from GVHD. Tissue Antigens. 2013;81(4):183–193. doi:10.1111/tan.1209023510414
   PubMedGoogle Scholar
• NegrinRS. Graft-versus-host disease versus graft-versus-leukemia. Hematology. 2015;2015(1):225–230. doi:10.1182/asheducation-2015.1.22526637726
   PubMed Web of Science ®Google Scholar
• ChangY-J, ZhaoX-Y, HuangX-J. Strategies for enhancing and preserving anti-leukemia effects without aggravating graft-versus-host disease. Front Immunol. 2018;9:3041. doi:10.3389/fimmu.2018.0304130619371
   PubMed Web of Science ®Google Scholar
• RobinsonJ, HalliwellJA, HayhurstJD, et al. IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2015;43(D1):D423–D431. doi:10.1093/nar/gku116125414341
   PubMed Web of Science ®Google Scholar
• AnasettiC, BeattyPG, StorbR, et al. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990;29(2):79–91. doi:10.1016/0198-8859(90)90071-V2249952
   PubMed Web of Science ®Google Scholar
• AyukF, BeelenDW, BornhäuserM, et al. Relative impact of HLA matching and non-HLA donor characteristics on outcomes of allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2018;24(12):2558–2567. doi:10.1016/j.bbmt.2018.06.02629966760
   PubMed Web of Science ®Google Scholar
• PiemonteseS, CiceriF, LabopinM, et al.; on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia. J Hematol Oncol. 2017;10(1):24. doi:10.1186/s13045-017-0394-2.28103944
   PubMed Web of Science ®Google Scholar
• KasamonYL, LuznikL, LeffellMS, et al. Nonmyeloablative HLA-haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on outcome. Biol Blood Marrow Transplant. 2010;16(4):482–489. doi:10.1016/j.bbmt.2009.11.01119925877
   PubMed Web of Science ®Google Scholar
• SolomonSR, AubreyMT, ZhangX, et al. Selecting the best donor for haploidentical transplant: impact of HLA, killer cell immunoglobulin-like receptor genotyping, and other clinical variables. Biol Blood Marrow Transplant. 2018;24(4):789–798. doi:10.1016/j.bbmt.2018.01.01329355721
   PubMed Web of Science ®Google Scholar
• FleischhauerK, ShawBE. HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities. Blood. 2017;130(9):1089–1096. doi:10.1182/blood-2017-03-74234628667011
   PubMed Web of Science ®Google Scholar
• FleischhauerK, ShawBE, GooleyT, et al. Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study. Lancet Oncol. 2012;13(4):366–374. doi:10.1016/S1470-2045(12)70004-922340965
   PubMed Web of Science ®Google Scholar
• PetersdorfEW, CarringtonM, O’hUiginC, et al. Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation: a retrospective cohort study. Lancet Haematol. 2020;7(1):e50–e60. doi:10.1016/S2352-3026(19)30208-X31669248
   PubMed Web of Science ®Google Scholar
• KollmanC, SpellmanSR, ZhangM-J, et al. The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy. Blood. 2016;127(2):260–267. doi:10.1182/blood-2015-08-66382326527675
   PubMed Web of Science ®Google Scholar
• KollmanC, HoweCWS, AnasettiC, et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood. 2001;98(7):2043–2051. doi:10.1182/blood.V98.7.204311567988
   PubMed Web of Science ®Google Scholar
• CanaaniJ, SavaniBN, LabopinM, et al. Donor age determines outcome in acute leukemia patients over 40 undergoing haploidentical hematopoietic cell transplantation. Am J Hematol. 2018;93(2):246–253. doi:10.1002/ajh.2496329114918
   PubMed Web of Science ®Google Scholar
• CiureaSO, ShahMV, SalibaRM, et al. Haploidentical transplantation for older patients with acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2018;24(6):1232–1236. doi:10.1016/j.bbmt.2017.09.00528918304
   PubMed Web of Science ®Google Scholar
• RezvaniAR, StorerBE, GuthrieKA, et al. Impact of donor age on outcome after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21(1):105–112. doi:10.1016/j.bbmt.2014.09.02125278458
   PubMed Web of Science ®Google Scholar
• MariottiJ, RaiolaAM, EvangelistaA, et al. Impact of donor age and kinship on clinical outcomes after T-cell–replete haploidentical transplantation with PT-Cy. Blood Adv. 2020;4(16):3900–3912. doi:10.1182/bloodadvances.202000162032813875
   PubMed Web of Science ®Google Scholar
• SternM, BrandR, de WitteT, et al. Female-versus-male alloreactivity as a model for minor histocompatibility antigens in hematopoietic stem cell transplantation. Am J Transplant. 2008;8(10):2149–2157. doi:10.1111/j.1600-6143.2008.02374.x18828773
   PubMed Web of Science ®Google Scholar
• KongtimP, Di StasiA, RondonG, et al. Can a female donor for a male recipient decrease the relapse rate for patients with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation?Biol Blood Marrow Transplant. 2015;21(4):713–719. doi:10.1016/j.bbmt.2014.12.01825540936
   PubMed Web of Science ®Google Scholar
• PasswegJR, BaldomeroH, BaderP, et al.; for the European Society for Blood and Marrow Transplantation (EBMT). Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant. 2015;50(4):476–482. doi:10.1038/bmt.2014.312.25642761
   PubMed Web of Science ®Google Scholar
• AnasettiC, LoganBR, LeeSJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367(16):1487–1496. doi:10.1056/NEJMoa120351723075175
   PubMed Web of Science ®Google Scholar
• ByrneM, SavaniBN, MohtyM, NaglerA. Peripheral blood stem cell versus bone marrow transplantation: a perspective from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Exp Hematol. 2016;44(7):567–573. doi:10.1016/j.exphem.2016.04.00527106798
   PubMed Web of Science ®Google Scholar
• SavaniBN, LabopinM, BlaiseD, et al. Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT. Haematologica. 2016;101(2):256–262. doi:10.3324/haematol.2015.13569926565001
   PubMed Web of Science ®Google Scholar
• TeipelR, OelschlägelU, WetzkoK, et al. Differences in cellular composition of peripheral blood stem cell grafts from healthy stem cell donors mobilized with either Granulocyte Colony-Stimulating Factor (G-CSF) alone or G-CSF and plerixafor. Biol Blood Marrow Transplant. 2018;24(11):2171–2177. doi:10.1016/j.bbmt.2018.06.02329935214
   PubMed Web of Science ®Google Scholar
• SchroederMA, RettigMP, LopezS, et al. Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft. Blood. 2017;129(19):2680–2692. doi:10.1182/blood-2016-09-73972228292947
   PubMed Web of Science ®Google Scholar
• FisherSA, LamikanraA, DoréeC, et al. Increased regulatory T cell graft content is associated with improved outcome in haematopoietic stem cell transplantation: a systematic review. Br J Haematol. 2017;176(3):448–463. doi:10.1111/bjh.1443328094847
   PubMed Web of Science ®Google Scholar
• EdingerM, HoffmannP, ErmannJ, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9(9):1144–1150. doi:10.1038/nm91512925844
   PubMed Web of Science ®Google Scholar
• SaraceniF, Shem-TovN, OlivieriA, NaglerA. Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective. Bone Marrow Transplant. 2015;50(7):886–891. doi:10.1038/bmt.2014.33025665044
   PubMed Web of Science ®Google Scholar
• DuvalM, KleinJP, HeW, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28(23):3730–3738. doi:10.1200/JCO.2010.28.885220625136
   PubMed Web of Science ®Google Scholar
• WalterRB, GyurkoczaB, StorerBE, et al. Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia. 2015;29(1):137–144. doi:10.1038/leu.2014.17324888275
   PubMed Web of Science ®Google Scholar
• ArakiD, WoodBL, OthusM, et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease–based definition of complete remission?J Clin Oncol. 2016;34(4):329–336. doi:10.1200/JCO.2015.63.382626668349
   PubMed Web of Science ®Google Scholar
• ShayegiN, KramerM, BornhäuserM, et al. The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML. Blood. 2013;122(1):83–92. doi:10.1182/blood-2012-10-46174923656730
   PubMed Web of Science ®Google Scholar
• NorkinM, KatragaddaL, ZouF, et al. Minimal residual disease by either flow cytometry or cytogenetics prior to an allogeneic hematopoietic stem cell transplant is associated with poor outcome in acute myeloid leukemia. Blood Cancer J. 2017;7(12):634. doi:10.1038/s41408-017-0007-x29176662
   PubMed Web of Science ®Google Scholar
• Jongen-LavrencicM, GrobT, HanekampD, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378(13):1189–1199. doi:10.1056/NEJMoa171686329601269
   PubMed Web of Science ®Google Scholar
• Rodríguez-ArbolíE, LabopinM, TischerJ, et al. FLAMSA-based reduced-intensity conditioning versus myeloablative conditioning in younger patients with relapsed/refractory acute myeloid leukemia with active disease at the time of allogeneic stem cell transplantation: an analysis from the acute leukemia working party of the European Society For Blood And Marrow Transplantation. Biol Blood Marrow Transplant. 2020;26(11):2165–2173. doi:10.1016/j.bbmt.2020.07.02032717436
   PubMed Web of Science ®Google Scholar
• UstunC, CourvilleEL, DeForT, et al. Myeloablative, but not reduced-intensity, conditioning overcomes the negative effect of flow-cytometric evidence of leukemia in acute myeloid leukemia. Biol Blood Marrow Transplant. 2016;22(4):669–675. doi:10.1016/j.bbmt.2015.10.02426551635
   PubMed Web of Science ®Google Scholar
• LintV. The combined effect of total body irradiation (TBI) and cyclosporin A (CyA) on the risk of relapse in patients with acute myeloid leukaemia undergoing allogeneic bone marrow transplantation: effect of TBI and CyA on post-transplant relapse in AML. Br J Haematol. 2000;108(1):99–104. doi:10.1046/j.1365-2141.2000.01809.x10651732
   PubMed Web of Science ®Google Scholar
• SchmidC, SchleuningM, LedderoseG, TischerJ, KolbH-J. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005;23(24):5675–5687. doi:10.1200/JCO.2005.07.06116110027
   PubMed Web of Science ®Google Scholar
• SteckelNK, GrothC, MikeschJ-H, et al. High-dose melphalan-based sequential conditioning chemotherapy followed by allogeneic haematopoietic stem cell transplantation in adult patients with relapsed or refractory acute myeloid leukaemia. Br J Haematol. 2018;180(6):840–853. doi:10.1111/bjh.1513729468631
   PubMed Web of Science ®Google Scholar
• DoppelhammerM, FraccaroliA, PrevalsekD, et al. Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning—a matched pair analysis. Ann Hematol. 2019;98(3):753–762. doi:10.1007/s00277-019-03593-230617644
   PubMed Web of Science ®Google Scholar
• StölzelF. From remission to cure: bypass or detour?Br J Haematol. 2018;180(3):317–318. doi:10.1111/bjh.1503129193005
   PubMed Web of Science ®Google Scholar
• CliftR, BucknerC, AppelbaumF, et al. Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens [see comments]. Blood. 1990;76(9):1867–1871. doi:10.1182/blood.V76.9.1867.18672224134
   PubMed Web of Science ®Google Scholar
• AoudjhaneM, LabopinM, GorinN, et al. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia. 2005;19(12):2304–2312.16193083
   PubMed Web of Science ®Google Scholar
• MartinoR, de WreedeL, FioccoM, et al.; for the Acute Leukemia Working Party the subcommittee for Myelodysplastic Syndromes of the Chronic Malignancies Working Party of the European group for Blood Marrow Transplantation Group (EBMT). Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with <10% BM blasts: a report from EBMT. Bone Marrow Transplant. 2013;48(6):761–770. doi:10.1038/bmt.2012.236.23208314
   PubMed Web of Science ®Google Scholar
• PasswegJR, BaldomeroH, GratwohlA, et al.; for the European Group for Blood and Marrow Transplantation (EBMT). The EBMT activity survey: 1990–2010. Bone Marrow Transplant. 2012;47(7):906–923. doi:10.1038/bmt.2012.66.22543746
   PubMed Web of Science ®Google Scholar
• LugerSM, RingdénO, ZhangM-J, et al. Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS. Bone Marrow Transplant. 2012;47(2):203–211. doi:10.1038/bmt.2011.6921441963
   PubMed Web of Science ®Google Scholar
• ScottBL, PasquiniMC, LoganBR, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35(11):1154–1161. doi:10.1200/JCO.2016.70.709128380315
   PubMed Web of Science ®Google Scholar
• ValcárcelD, MartinoR, PiñanaJL, SierraJ. Allogeneic stem cell transplantation after reduced-intensity conditioning for acute myeloid leukaemia: impact of chronic graft-versus-host disease. Curr Opin Oncol. 2009;21:S35–S37.19561412
   PubMedGoogle Scholar
• RosenowF, BerkemeierA, KrugU, et al. CD34+ lineage specific donor cell chimerism for the diagnosis and treatment of impending relapse of AML or myelodysplastic syndrome after allo-SCT. Bone Marrow Transplant. 2013;48(8):1070–1076. doi:10.1038/bmt.2013.223376821
   PubMed Web of Science ®Google Scholar
• ZeiserR, BlazarBR. Acute graft-versus-host disease — biologic process, prevention, and therapy. N Engl J Med. 2017;377(22):2167–2179. doi:10.1056/NEJMra160933729171820
   PubMed Web of Science ®Google Scholar
• FerraraJL, LevineJE, ReddyP, HollerE. Graft-versus-host disease. Lancet. 2009;373(9674):1550–1561. doi:10.1016/S0140-6736(09)60237-319282026
   PubMed Web of Science ®Google Scholar
• KolbH-J. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112(12):4371–4383. doi:10.1182/blood-2008-03-07797419029455
   PubMed Web of Science ®Google Scholar
• LuznikL, O’DonnellPV, SymonsHJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641–650. doi:10.1016/j.bbmt.2008.03.00518489989
   PubMed Web of Science ®Google Scholar
• LuznikL, O’DonnellPV, FuchsEJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Haploidentical Bone Marrow Transplant. 2012;39(6):683–693. doi:10.1053/j.seminoncol.2012.09.005
   Web of Science ®Google Scholar
• CiureaSO, ZhangM-J, BacigalupoAA, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126(8):1033–1040. doi:10.1182/blood-2015-04-63983126130705
   PubMed Web of Science ®Google Scholar
• MielcarekM, FurlongT, O’DonnellPV, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502–1508. doi:10.1182/blood-2015-10-67207126764356
   PubMed Web of Science ®Google Scholar
• RobinsonTM, O’DonnellPV, FuchsEJ, LuznikL. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Altern Donor Transplant. 2016;53(2):90–97. doi:10.1053/j.seminhematol.2016.01.005
   Web of Science ®Google Scholar
• GangulyS, RossDB, Panoskaltsis-MortariA, et al. Donor CD4+ Foxp3+ regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice. Blood. 2014;124(13):2131–2141. doi:10.1182/blood-2013-10-52587325139358
   PubMed Web of Science ®Google Scholar
• WachsmuthLP, PattersonMT, EckhausMA, VenzonDJ, GressRE, KanakryCG. Posttransplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression. J Clin Invest. 2019;129(6):2357–2373. doi:10.1172/JCI12421830913039
   PubMed Web of Science ®Google Scholar
• BlazarBR, MacDonaldKPA, HillGR. Immune regulatory cell infusion for graft-versus-host disease prevention and therapy. Blood. 2018;131(24):2651–2660. doi:10.1182/blood-2017-11-78586529728401
   PubMed Web of Science ®Google Scholar
• BertainaA, RoncaroloMG. Graft engineering and adoptive immunotherapy: new approaches to promote immune tolerance after hematopoietic stem cell transplantation. Front Immunol. 2019;10:13.30728822
   PubMed Web of Science ®Google Scholar
• KanakryCG, Bolaños-MeadeJ, KasamonYL, et al. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. Blood. 2017;129(10):1389–1393. doi:10.1182/blood-2016-09-73782528049637
   PubMed Web of Science ®Google Scholar
• McCurdySR, KanakryCG, TsaiH-L, et al. Grade II acute graft-versus-host disease and higher nucleated cell graft dose improve progression-free survival after HLA-haploidentical transplant with post-transplant cyclophosphamide. Biol Blood Marrow Transplant. 2018;24(2):343–352. doi:10.1016/j.bbmt.2017.10.02329055682
   PubMed Web of Science ®Google Scholar
• BlazarBR, MurphyWJ, AbediM. Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol. 2012;12(6):443–458. doi:10.1038/nri321222576252
   PubMed Web of Science ®Google Scholar
• AshRC, HorowitzMM, GaleRP, et al. Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion. Bone Marrow Transplant. 1991;7(6):443–452.1873591
   PubMed Web of Science ®Google Scholar
• LocatelliF, MerliP, PagliaraD, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion. Blood. 2017;130(5):677–685. doi:10.1182/blood-2017-04-77976928588018
   PubMed Web of Science ®Google Scholar
• MartelliMF, Di IanniM, RuggeriL, et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014;124(4):638–644. doi:10.1182/blood-2014-03-56440124923299
   PubMed Web of Science ®Google Scholar
• Di StasiA, TeyS-K, DottiG, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365(18):1673–1683. doi:10.1056/NEJMoa110615222047558
   PubMed Web of Science ®Google Scholar
• ZhangY-L, ZhuY, XiaoQ, WangL, LiuL, LuoX-H. Cytomegalovirus infection is associated with AML relapse after allo-HSCT: a meta-analysis of observational studies. Ann Hematol. 2019;98(4):1009–1020. doi:10.1007/s00277-018-3585-130666434
   PubMed Web of Science ®Google Scholar
• KwekkeboomJ. Potential beneficial effects of cytomegalovirus infection after transplantation. Front Immunol. 2018;9:11.29416536
   PubMed Web of Science ®Google Scholar
• LjungmanP, BrandR, HoekJ, et al. Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European Group for Blood and Marrow Transplantation. Clin Infect Dis. 2014;59(4):473–481. doi:10.1093/cid/ciu36424850801
   PubMed Web of Science ®Google Scholar
• HorowitzA, GuethleinLA, Nemat-GorganiN, et al. Regulation of adaptive NK cells and CD8 T cells by HLA-C correlates with allogeneic hematopoietic cell transplantation and with cytomegalovirus reactivation. J Immunol. 2015;195(9):4524. doi:10.4049/jimmunol.140199026416275
   PubMed Web of Science ®Google Scholar
• CesaroS, CrocchioloR, TridelloG, et al. Comparable survival using a CMV-matched or a mismatched donor for CMV+ patients undergoing T-replete haplo-HSCT with PT-Cy for acute leukemia: a study of behalf of the infectious diseases and acute leukemia working parties of the EBMT. Bone Marrow Transplant. 2018;53(4):422–430. doi:10.1038/s41409-017-0016-129330396
   PubMed Web of Science ®Google Scholar
• YewPY, AlachkarH, YamaguchiR, et al. Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2015;50(9):1227–1234. doi:10.1038/bmt.2015.13326052909
   PubMed Web of Science ®Google Scholar
• NovielloM, ManfrediF, RuggieroE, et al. Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT. Nat Commun. 2019;10(1):1065. doi:10.1038/s41467-019-08871-130911002
   PubMed Web of Science ®Google Scholar
• SchmidC, LabopinM, SchaapN, et al. Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation in acute leukaemia - a matched pair analysis by the Acute Leukaemia Working Party of EBMT. Br J Haematol. 2019;184(5):782–787. doi:10.1111/bjh.1569130467839
   PubMed Web of Science ®Google Scholar
• BornhauserM, OelschlaegelU, PlatzbeckerU, et al. Monitoring of donor chimerism in sorted CD34+ peripheral blood cells allows the sensitive detection of imminent relapse after allogeneic stem cell transplantation. Haematologica. 2009;94(11):1613–1617. doi:10.3324/haematol.2009.00776519880783
   PubMed Web of Science ®Google Scholar
• GrecoR, OliveiraG, StanghelliniMTL, et al. Improving the safety of cell therapy with the TK-suicide gene. Front Pharmacol. 2015;6. doi:10.3389/fphar.2015.00095
   PubMed Web of Science ®Google Scholar
• AndersonBE, McNiffJ, YanJ, et al. Memory CD4+ T cells do not induce graft-versus-host disease. J Clin Invest. 2003;112(1):101–108. doi:10.1172/JCI1760112840064
   PubMed Web of Science ®Google Scholar
• MufflyL, SheehanK, ArmstrongR, et al. Infusion of donor-derived CD8+ memory T cells for relapse following allogeneic hematopoietic cell transplantation. Blood Adv. 2018;2(6):681–690. doi:10.1182/bloodadvances.201701210429572391
   PubMed Web of Science ®Google Scholar
• GhisoA, RaiolaAM, GualandiF, et al. DLI after haploidentical BMT with post-transplant CY. Bone Marrow Transplant. 2015;50(1):56–61. doi:10.1038/bmt.2014.21725310304
   PubMed Web of Science ®Google Scholar
• SchroederT, RachlisE, BugG, et al. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions—a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant. 2015;21(4):653–660. doi:10.1016/j.bbmt.2014.12.01625540937
   PubMed Web of Science ®Google Scholar
• RuggeriL, CapanniM, UrbaniE, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097. doi:10.1126/science.106844011896281
   PubMed Web of Science ®Google Scholar
• CooleyS, TrachtenbergE, BergemannTL, et al. Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood. 2009;113(3):726–732. doi:10.1182/blood-2008-07-17192618945962
   PubMed Web of Science ®Google Scholar
• MichaelisSU, MezgerM, BornhäuserM, et al. KIR haplotype B donors but not KIR-ligand mismatch result in a reduced incidence of relapse after haploidentical transplantation using reduced intensity conditioning and CD3/CD19-depleted grafts. Ann Hematol. 2014;93(9):1579–1586. doi:10.1007/s00277-014-2084-224771045
   PubMed Web of Science ®Google Scholar
• MancusiA, RuggeriL, UrbaniE, et al. Haploidentical hematopoietic transplantation from KIR ligand–mismatched donors with activating KIRs reduces nonrelapse mortality. Blood. 2015;125(20):3173–3182. doi:10.1182/blood-2014-09-59999325769621
   PubMed Web of Science ®Google Scholar
• LeungW, IyengarR, TurnerV, et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol. 2004;172(1):644–650. doi:10.4049/jimmunol.172.1.64414688377
   PubMed Web of Science ®Google Scholar
• RuggeriL, MancusiA, CapanniM, et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007;110(1):433–440. doi:10.1182/blood-2006-07-03868717371948
   PubMed Web of Science ®Google Scholar
• RuggeriL, VagoL, EikemaD-J, et al. Natural killer cell alloreactivity in HLA-haploidentical hematopoietic transplantation: a study on behalf of the CTIWP of the EBMT. Bone Marrow Transplant. 2021;56(8):1900–1907. doi:10.1038/s41409-021-01259-033767404
   PubMed Web of Science ®Google Scholar
• StrongRK, McFarlandBJ. NKG2D and related immunoreceptors. Adv Protein Chem. 2004;68:281–312. doi:10.1016/S0065-3233(04)68008-915500864
   PubMedGoogle Scholar
• PaczullaAM, RothfelderK, RaffelS, et al. Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion. Nature. 2019;572(7768):254–259. doi:10.1038/s41586-019-1410-131316209
   PubMed Web of Science ®Google Scholar
• Sanchez-CorreaB, GayosoI, BerguaJM, et al. Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients. Immunol Cell Biol. 2012;90(1):109–115. doi:10.1038/icb.2011.1521383766
   PubMed Web of Science ®Google Scholar
• FauriatC, Just-LandiS, MalletF, et al. Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood. 2007;109(1):323–330. doi:10.1182/blood-2005-08-02797916940427
   PubMed Web of Science ®Google Scholar
• MathewNR, BaumgartnerF, BraunL, et al. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018;24(3):282–291. doi:10.1038/nm.448429431743
   PubMed Web of Science ®Google Scholar
• LitjensNHR, van der WagenL, KuballJ, KwekkeboomJ. Potential beneficial effects of cytomegalovirus infection after transplantation. Front Immunol. 2018;9:389. doi:10.3389/fimmu.2018.0038929545802
   PubMed Web of Science ®Google Scholar
• CiureaSO, SchaferJR, BassettR, et al. Phase 1 clinical trial using mbIL21 ex vivo–expanded donor-derived NK cells after haploidentical transplantation. Blood. 2017;130(16):1857–1868. doi:10.1182/blood-2017-05-78565928835441
   PubMed Web of Science ®Google Scholar
• MaggsL, KinsellaF, ChanYLT, et al. The number of CD56dim NK cells in the graft has a major impact on risk of disease relapse following allo-HSCT. Blood Adv. 2017;1(19):1589–1597. doi:10.1182/bloodadvances.201700863129296800
   PubMed Web of Science ®Google Scholar
• SavaniBN, MielkeS, AdamsS, et al. Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia. Leukemia. 2007;21(10):2145–2152. doi:10.1038/sj.leu.240489217673900
   PubMed Web of Science ®Google Scholar
• BugginsAGS, MilojkovicD, ArnoMJ, et al. Microenvironment produced by acute myeloid leukemia cells prevents T cell activation and proliferation by inhibition of NF-κB, c-Myc, and pRb pathways. J Immunol. 2001;167(10):6021–6030. doi:10.4049/jimmunol.167.10.602111698483
   PubMed Web of Science ®Google Scholar
• ColpittsSL, StonierSW, StoklasekTA, et al. Transcriptional regulation of IL-15 expression during hematopoiesis. J Immunol. 2013;191(6):3017–3024. doi:10.4049/jimmunol.130138923966624
   PubMed Web of Science ®Google Scholar
• CieriN, CamisaB, CocchiarellaF, et al. IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood. 2013;121(4):573–584. doi:10.1182/blood-2012-05-43171823160470
   PubMed Web of Science ®Google Scholar
• ThiantS, Yakoub-AghaI, MagroL, et al. Plasma levels of IL-7 and IL-15 in the first month after myeloablative BMT are predictive biomarkers of both acute GVHD and relapse. Bone Marrow Transplant. 2010;45(10):1546–1552. doi:10.1038/bmt.2010.1320190846
   PubMed Web of Science ®Google Scholar
• BurchertA, BugG, FritzLV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3 –internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38(26):2993–3002. doi:10.1200/JCO.19.0334532673171
   PubMed Web of Science ®Google Scholar
• MunnDH, SharmaMD, BabanB, et al. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity. 2005;22(5):633–642. doi:10.1016/j.immuni.2005.03.01315894280
   PubMed Web of Science ®Google Scholar
• MussaiF, De SantoC, Abu-DayyehI, et al. Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood. 2013;122(5):749–758. doi:10.1182/blood-2013-01-48012923733335
   PubMed Web of Science ®Google Scholar
• HäuslerSFM, Montalbán Del BarrioI, StrohscheinJ, et al. Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity. Cancer Immunol Immunother. 2011;60(10):1405–1418. doi:10.1007/s00262-011-1040-421638125
   PubMed Web of Science ®Google Scholar
• Beavis PaulA, StaggJ, DarcyPK, SmythMJ. CD73: a potent suppressor of antitumor immune responses. Trends Immunol. 2012;33(5):231–237. doi:10.1016/j.it.2012.02.00922487321
   PubMed Web of Science ®Google Scholar
• DulphyN, HenryG, HemonP, et al. Contribution of CD39 to the immunosuppressive microenvironment of acute myeloid leukaemia at diagnosis. Br J Haematol. 2014;165(5):722–725. doi:10.1111/bjh.1277424666252
   PubMed Web of Science ®Google Scholar
• UhlFM, ChenS, O’SullivanD, et al. Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans. Sci Transl Med. 2020;12(567):eabb8969. doi:10.1126/scitranslmed.abb896933115954
   PubMed Web of Science ®Google Scholar
• JanM, LeventhalMJ, MorganEA, et al. Recurrent genetic HLA loss in AML relapsed after matched unrelated allogeneic hematopoietic cell transplantation. Blood Adv. 2019;3(14):2199–2204. doi:10.1182/bloodadvances.201900044531324640
   PubMed Web of Science ®Google Scholar
• VagoL, PernaSK, ZanussiM, et al. Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med. 2009;361(5):478–488. doi:10.1056/NEJMoa081103619641204
   PubMed Web of Science ®Google Scholar
• WaterhouseM, PfeiferD, PanticM, EmmerichF, BertzH, FinkeJ. Genome-wide profiling in AML patients relapsing after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17(10):1450–1459.e1. doi:10.1016/j.bbmt.2011.07.01221781950
   PubMed Web of Science ®Google Scholar
• StölzelF, HackmannK, KuithanF, et al. Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation. Transplantation. 2012;93(7):744–749. doi:10.1097/TP.0b013e318248111322314337
   PubMed Web of Science ®Google Scholar
• MasudaK, HirakiA, FujiiN, et al. Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts. Cancer Sci. 2007;98(1):102–108. doi:10.1111/j.1349-7006.2006.00356.x17083564
   PubMed Web of Science ®Google Scholar
• DuboisV, Sloan-BénaF, CesbronA, et al. Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy. Leukemia. 2012;26(9):2079–2085. doi:10.1038/leu.2012.6822488219
   PubMed Web of Science ®Google Scholar
• CrucittiL, CrocchioloR, ToffaloriC, et al. Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation. Leukemia. 2015;29(5):1143–1152. doi:10.1038/leu.2014.31425371177
   PubMed Web of Science ®Google Scholar
• BarrettJ, BlazarBR. Genetic trickery — escape of leukemia from immune attack. N Engl J Med. 2009;361(5):524–525. doi:10.1056/NEJMe090317719641211
   PubMed Web of Science ®Google Scholar
• VagoL, CiceriF. Choosing the alternative. Biol Blood Marrow Transplant. 2017;23(11):1813–1814. doi:10.1016/j.bbmt.2017.09.00928939457
   PubMed Web of Science ®Google Scholar
• RovattiPE, GambacortaV, LorentinoF, CiceriF, VagoL. Mechanisms of leukemia immune evasion and their role in relapse after haploidentical hematopoietic cell transplantation. Front Immunol. 2020;11:147. doi:10.3389/fimmu.2020.0014732158444
   PubMed Web of Science ®Google Scholar
• ZhukovskyEA, MorseRJ, MausMV. Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection. Antigen Process Spec Sect New Concepts Antib Ther. 2016;40:24–35. doi:10.1016/j.coi.2016.02.006
   Google Scholar
• ToffaloriC, ZitoL, GambacortaV, et al. Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation. Nat Med. 2019;25(4):603–611. doi:10.1038/s41591-019-0400-z30911134
   PubMed Web of Science ®Google Scholar
• ChristopherMJ, PettiAA, RettigMP, et al. Immune escape of relapsed AML cells after allogeneic transplantation. N Engl J Med. 2018;379(24):2330–2341. doi:10.1056/NEJMoa180877730380364
   PubMed Web of Science ®Google Scholar
• NordeWJ, MaasF, HoboW, et al. PD-1/PD-L1 interactions contribute to functional T-cell impairment in patients who relapse with cancer after allogeneic stem cell transplantation. Cancer Res. 2011;71(15):5111–5122. doi:10.1158/0008-5472.CAN-11-010821659460
   PubMed Web of Science ®Google Scholar
• GreilR, HuttererE, HartmannTN, PleyerL. Reactivation of dormant anti-tumor immunity – a clinical perspective of therapeutic immune checkpoint modulation. Cell Commun Signal. 2017;15(1):5. doi:10.1186/s12964-016-0155-928100240
   PubMed Web of Science ®Google Scholar
• AlbringJC, InselmannS, SauerT, et al. PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation. Bone Marrow Transplant. 2017;52(2):317–320. doi:10.1038/bmt.2016.27427892950
   PubMed Web of Science ®Google Scholar
• DavidsMS, KimHT, BachireddyP, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016;375(2):143–153. doi:10.1056/NEJMoa160120227410923
   PubMed Web of Science ®Google Scholar
• IjazA, KhanAY, MalikSU, et al. Significant risk of graft-versus-host disease with exposure to checkpoint inhibitors before and after allogeneic transplantation. Biol Blood Marrow Transplant. 2019;25(1):94–99. doi:10.1016/j.bbmt.2018.08.02830195074
   PubMed Web of Science ®Google Scholar
• DaverN, BodduP, Garcia-ManeroG, et al. Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Leukemia. 2018;32(5):1094–1105. doi:10.1038/s41375-018-0070-829487386
   PubMed Web of Science ®Google Scholar
• DaverN, Garcia-ManeroG, BasuS, et al. Efficacy, safety, and biomarkers of response to azacitidine and nivolumab in relapsed/refractory acute myeloid leukemia: a nonrandomized, open-label, phase II study. Cancer Discov. 2019;9(3):370–383. doi:10.1158/2159-8290.CD-18-077430409776
   PubMed Web of Science ®Google Scholar
• GhoshA, BarbaP, PeralesM. Checkpoint inhibitors in AML: are we there yet?Br J Haematol. 2020;188(1):159–167. doi:10.1111/bjh.1635831808941
   PubMed Web of Science ®Google Scholar
• EhxG, LaroucheJ-D, DuretteC, et al. Atypical acute myeloid leukemia-specific transcripts generate shared and immunogenic MHC class-I-associated epitopes. Immunity. 2021;54(4):737–752.e10. doi:10.1016/j.immuni.2021.03.00133740418
   PubMed Web of Science ®Google Scholar
• ZeiserR, VagoL. Mechanisms of immune escape after allogeneic hematopoietic cell transplantation. Blood. 2019;133(12):1290–1297. doi:10.1182/blood-2018-10-84682430578254
   PubMed Web of Science ®Google Scholar
• AmbinderAJ, LevisM. Potential targeting of FLT3 acute myeloid leukemia. Haematologica. 2020;106(3):671–681. doi:10.3324/haematol.2019.240754
   Web of Science ®Google Scholar
• DaverN, SchlenkRF, RussellNH, LevisMJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299–312. doi:10.1038/s41375-018-0357-930651634
   PubMed Web of Science ®Google Scholar
• KottaridisPD, GaleRE, FrewME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98(6):1752–1759. doi:10.1182/blood.V98.6.175211535508
   PubMed Web of Science ®Google Scholar
• StoneRM, MandrekarSJ, SanfordBL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454–464. doi:10.1056/NEJMoa161435928644114
   PubMed Web of Science ®Google Scholar
• CortesJE, KhaledS, MartinelliG, et al. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019;20(7):984–997. doi:10.1016/S1470-2045(19)30150-031175001
   PubMed Web of Science ®Google Scholar
• PerlAE, MartinelliG, CortesJE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3 -mutated AML. N Engl J Med. 2019;381(18):1728–1740. doi:10.1056/NEJMoa190268831665578
   PubMed Web of Science ®Google Scholar
• MillCP, FiskusW, DiNardoCD, et al. RUNX1-targeted therapy for AML expressing somatic or germline mutation in RUNX1. Blood. 2019;134(1):59–73. doi:10.1182/blood.201889398231023702
   PubMed Web of Science ®Google Scholar
• PhillipsDC, JinS, GregoryGP, et al. A novel CDK9 inhibitor increases the efficacy of venetoclax (ABT-199) in multiple models of hematologic malignancies. Leukemia. 2020;34(6):1646–1657. doi:10.1038/s41375-019-0652-031827241
   PubMed Web of Science ®Google Scholar
• BogenbergerJ, WhatcottC, HansenN, et al. Combined venetoclax and alvocidib in acute myeloid leukemia. Oncotarget. 2017;8(63):107206–107222. doi:10.18632/oncotarget.2228429291023
   PubMedGoogle Scholar
• OellerichT, MohrS, CorsoJ, et al. FLT3-ITD and TLR9 use Bruton tyrosine kinase to activate distinct transcriptional programs mediating AML cell survival and proliferation. Blood. 2015;125(12):1936–1947. doi:10.1182/blood-2014-06-58521625605370
   PubMed Web of Science ®Google Scholar
• GöllnerS, OellerichT, Agrawal-SinghS, et al. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia. Nat Med. 2017;23(1):69–78. doi:10.1038/nm.424727941792
   PubMed Web of Science ®Google Scholar
• AtanackovicD, LuetkensT, KlothB, et al. Cancer-testis antigen expression and its epigenetic modulation in acute myeloid leukemia. Am J Hematol. 2011;86(11):918–922. doi:10.1002/ajh.2214121898529
   PubMed Web of Science ®Google Scholar
• GoodyearO, AgathanggelouA, Novitzky-BassoI, et al. Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 2010;116(11):1908–1918. doi:10.1182/blood-2009-11-24947420530795
   PubMed Web of Science ®Google Scholar
• GoodyearOC, DennisM, JilaniNY, et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood. 2012;119(14):3361–3369. doi:10.1182/blood-2011-09-37704422234690
   PubMed Web of Science ®Google Scholar
• ChoiJ, RitcheyJ, PriorJL, et al. In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia. Blood. 2010;116(1):129–139. doi:10.1182/blood-2009-12-25725320424188
   PubMed Web of Science ®Google Scholar
• ØrskovAD, TreppendahlMB, SkovboA, et al. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients: a rationale for combined targeting of PD-1 and DNA methylation. Oncotarget. 2015;6(11):9612–9626. doi:10.18632/oncotarget.332425823822
   PubMed Web of Science ®Google Scholar
• LaportGG, SheehanK, BakerJ, et al. Adoptive immunotherapy with cytokine-induced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17(11):1679–1687. doi:10.1016/j.bbmt.2011.05.01221664472
   PubMed Web of Science ®Google Scholar