Acute myeloid leukaemia relapse after allogeneic haematopoietic stem cell transplantation: Mechanistic diversity and therapeutic directions.
T-cell exhaustion
acute myeloid leukaemia
allogeneic stem cell transplantation
immune checkpoint molecules
immune escape
relapse
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
28
08
2023
received:
11
07
2023
accepted:
12
09
2023
medline:
29
11
2023
pubmed:
3
10
2023
entrez:
3
10
2023
Statut:
ppublish
Résumé
Emerging biological and clinical data, along with advances in new technologies, have exposed the mechanistic diversity in post-haematopoietic stem cell transplant (HCT) relapse. Post-HCT relapse mechanisms are relevant for guiding sophisticated selection of therapeutic interventions and identification of areas for further research. Clonal evolution and emergence of resistant leukemic strains is a common mechanism shared by relapse post-chemotherapy and post-HCT, other mechanisms such as leukemic immune escape and donor T cell exhaustion are unique entities to post-HCT relapse. Due to diversity in the mechanisms behind post-HCT relapse, the subsequent clinical approach relies on clinician discretion, rather than objective evidence. Lack of standardized selection based on post-HCT relapse mechanism(s) could be a contributing factor to observed poor outcomes. Therapeutic strategies including donor lymphocyte infusion (DLI), second transplant, immunotherapies, hypomethylating agents, and targeted strategies are supported options and efficacy may be enhanced when post-HCT AML relapse mechanism is established and guides treatment selection. This review aims, through compilation of supporting studies, to describe mechanisms of post-HCT relapse and their implications for subsequent treatment selection and inspiration for future research.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
722-735Informations de copyright
© 2023 British Society for Haematology and John Wiley & Sons Ltd.
Références
Ghazawi FM, Ramanakumar AV, Alakel A, Lagacé F, Chen A, Le M, et al. Incidence of acute myeloid leukemia: a regional analysis of Canada. Cancer. 2020;126:1356-1361.
Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021;11:41.
Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001;411:385-389.
Medeiros BC, Chan SM, Daver NG, Jonas BA, Pollyea DA. Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia. Am J Hematol. 2019;94:803-811.
Bejanyan N, Weisdorf DJ, Logan BR, Wang HL, Devine SM, de Lima M, 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.
Stratmann S, Yones SA, Mayrhofer M, Norgren N, Skaftason A, Sun J, et al. Genomic characterization of relapsed acute myeloid leukemia reveals novel putative therapeutic targets. Blood Adv. 2021;5(3):900-912.
Giacopelli B, Wang M, Cleary A, Wu YZ, Schultz AR, Schmutz M, et al. DNA methylation epitypes highlight underlying developmental and disease pathways in acute myeloid leukemia. Genome Res. 2021;31(5):747-761.
Toffalori C, Zito L, Gambacorta V, Riba M, Oliveira G, Bucci G, et al. Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation. Nat Med. 2019;25(4):603-611.
Morita K, Wang F, Jahn K, Hu T, Tanaka T, Sasaki Y, et al. Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics. Nat Commun. 2020;11(1):2823.
Ediriwickrema A, Aleshin A, Reiter JG, Corces MR, Kohnke T, Stafford M, et al. Single-cell mutational profiling enhances the clinical evaluation of AML MRD. Blood Adv. 2020;4(5):943-952.
Caiado F, Maia-Silva D, Jardim C, Schmolka N, Carvalho T, Reforço C, et al. Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection. Nat Commun. 2019;10(1):5451.
Smith CC, Levis MJ, Perl AE, Hill JE, Rosales M, Bahceci E. Molecular profile of FLT3 mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib. Blood Adv. 2022;6(7):2144-2155.
Cohler Peretz CA, McGary LHF, Kumar TF, Jackson JH, Jacob J, Durruthy-Durruthy R, et al. Single cell sequencing reveals evolution of tumor heterogeneity of acute myeloid leukemia on quizartinib. Blood. 2019;134(Suppl_1):1440.
Vago L. Clonal evolution and immune evasion in post transplantation relapses. Hematology Am Soc Hematol Educ Program. 2019;2019(1):610-616.
Quek L, Ferguson P, Metzner M, Ahmed I, Kennedy A, Garnett C, et al. Mutational analysis of disease relapse in patients allografted for acute myeloid leukemia. Blood Adv. 2016;1(3):193-204.
Vosberg S, Hartmann L, Metzeler KH, Konstandin NP, Schneider S, Varadharajan A, et al. Relapse of acute myeloid leukemia after allogeneic stem cell transplantation is associated with gain of WT1 alterations and high mutation load. Haematologica. 2018;103:e581-e584.
Kim TH, Moon JH, Ahn JS, Kim YK, Lee SS, Ahn SY, et al. Next-generation sequencing based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse. Blood. 2018;132(15):1604-1613.
Christopher MJ, Petti AA, Rettig MP, Miller CA, Chendamarai E, Duncavage EJ, et al. Immune escape of relapsed AML cells after allogeneic transplantation. N Engl J Med. 2018;379(24):2330-2341.
Wang A, Li W, Zhao F, Zheng Z, Yang T, Wang S, et al. Clinical characteristics and outcome analysis for HLA loss patients following partially mismatched related donor transplantation using HLA chimerism for loss of heterozygosity analysis by next-generation sequencing. Cell Transplant. 2022;31:096368972211029.
Jan M, Leventhal MJ, Morgan EA, Wengrod JC, Nag A, Drinan SD, et al. Recurrent genetic HLA loss in AML relapsed after matched unrelated allogeneic hematopoietic cell transplantation. Blood Adv. 2019;3(14):2199-2204.
Vago L, Perna SK, Zanussi M, Mazzi B, Stanghellini MTL, Perrelli NF, et al. Genomic loss of the mismatched HLA locus in leukemia is a major mechanism of in vivo escape from T cell immunosurveillance following haploidentical HSCT. Blood. 2008;112(11):828.
Vago L, Stanghellini MTL, Clerici D, Crotta A, Messina C, Forno B, et al. Loss of mismatched HLA as a mechanism of leukemia immune escape in family haploidentical and unrelated HSCT: analysis of 103 transplants from alternative donors. Blood. 2009;114(22):203.
Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, et al. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy article. Nat Immunol. 2018;19(1):76-84.
Berglund A, Mills M, Putney RM, Hamaidi I, Mulé J, Kim S. Methylation of immune synapse genes modulates tumor immunogenicity. J Clin Investig. 2020;130(2):974-980.
Deng M, Gui X, Kim J, Xie L, Chen W, Li Z, et al. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature. 2018;562(7728):605-609.
Galli S, Zlobec I, Schürch C, Perren A, Ochsenbein AF, Banz Y. CD47 protein expression in acute myeloid leukemia: a tissue microarray-based analysis. Leuk Res. 2015;39(7):749-756.
Gournay V, Vallet N, Peux V, Vera K, Bordenave J, Lambert M, et al. Immune landscape after allo-HSCT: tigit- and CD161-expressing CD4 T cells are associated with subsequent leukemia relapse. Blood. 2022;140(11):1305-1321. https://doi.org/10.1182/blood.2022015522
Sakoda T, Kikushige Y, Harada T, Irifune H, Hayashi M, Yoshimoto G, et al. Evaluation of tim-3-positive LSCs post allo-SCT is a highly sensitive strategy to predict AML relapses. Blood. 2019;134(Suppl_1):2702. https://doi.org/10.1182/blood-2019-127779
Williams P, Basu S, Garcia-Manero G, Hourigan CS, Oetjen KA, Cortes JE, et al. The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia. Cancer. 2018;125(9):1470-1481. https://doi.org/10.1002/cncr.31896
Xu ZJ, Zhang XL, Jin Y, Wang SS, Gu Y, Ma JC, et al. Pan-cancer analysis reveals distinct clinical, genomic, and immunological features of the LILRB immune checkpoint family in acute myeloid leukemia. Mol Ther Oncolytics. 2022;26:88-104.
Bachireddy P, Hainz U, Rooney M, Pozdnyakova O, Aldridge J, Zhang W, et al. Reversal of in situ T-cell exhaustion during effective human antileukemia responses to donor lymphocyte infusion. Blood. 2014;123(9):1412-1421.
Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, et al. PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J. 2015;5(7):e330.
Liu L, Chang YJ, Xu LP, Zhang XH, Wang Y, Liu KY, et al. Reversal of T cell exhaustion by the first donor lymphocyte infusion is associated with the persistently effective antileukemic responses in patients with relapsed AML after allo-HSCT. Biol Blood Marrow Transplant. 2018;24(7):1350-1359.
Minnie SA, Waltner OG, Ensbey KS, Nemychenkov NS, Schmidt CR, Bhise SS, et al. Depletion of exhausted alloreactive T cells enables targeting of stem-like memory T cells to generate tumor-specific immunity. Sci Immunol. 2022;7(76):eabo3420.
Norde WJ, Maas F, Hobo W, Korman A, Quigley M, Kester MGD, 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.
Noviello M, Manfredi F, Ruggiero E, Perini T, Oliveira G, Cortesi F, et al. Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT. Nat Commun. 2019;10(1):1065.
Rovatti PE, Gambacorta V, Lorentino F, Ciceri F, Vago L. Mechanisms of leukemia immune evasion and their role in relapse after haploidentical hematopoietic cell transplantation. Front Immunol. 2020;11:147.
Ciotti G, Marconi G, Martinelli G. Hypomethylating agent-based combination therapies to treat post-hematopoietic stem cell transplant relapse of acute myeloid leukemia. Front Oncol. 2022;11:810387.
Loo YH, Bell E, Ettayebi I, de Almeida FC, Boukhaled GM, Shen SY, et al. DNA hypomethylating agents increase activation and cytolytic activity of CD8+ T cells. Mol Cell. 2021;81(7):1469-1483.e8.
Peton B, Valerio M, Taniguchi M, Rodriguez I, Nafie E, Marcucci G, et al. The impact of hypomethylating agents and BCL-2 inhibitor on HLA expression on THP-1 cells. Blood. 2021;138(Suppl. 1):3990.
Bashey A, Medina B, Corringham S, Pasek M, Carrier E, Vrooman L, et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood. 2009;113(7):1581-1588.
Davids MS, Kim HT, Costello C, Herrera AF, Locke FL, Maegawa RO, et al. A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation. Blood. 2020;135(24):2182-2191.
Feng D, Gip P, McKenna KM, Zhao F, Mata O, Choi TS, et al. Combination treatment with 5F9 and azacitidine enhances phagocytic elimination of acute myeloid leukemia. Blood. 2018;132(Suppl. 1):2729.
Guillaume T, Malard F, Magro L, Labopin M, Tabrizi R, Borel C, et al. Prospective phase II study of prophylactic low-dose azacitidine and donor lymphocyte infusions following allogeneic hematopoietic stem cell transplantation for high-risk acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant. 2019;54(11):1815-1826. https://doi.org/10.1038/s41409-019-0536-y
Koestner W, Hapke M, Herbst J, Klein C, Welte K, Fruehauf J, et al. PD-L1 blockade effectively restores strong graft-versus-leukemia effects without graft-versus-host disease after delayed adoptive transfer of T-cell receptor gene-engineered allogeneic CD8+ T cells. Blood. 2011;117(3):1030-1041. https://doi.org/10.1182/blood-2010-04-283119
Sallman DA, Asch AS, Al Malki MM, Lee DJ, Donnellan WB, Marcucci G, et al. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results. Blood. 2019;134(Suppl_1):569.
Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng Q-R, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2013;28(6):1280-1288. https://doi.org/10.1038/leu.2013.355
Dobosz P, Stempor PA, Ramírez Moreno M, Bulgakova NA. Transcriptional and post transcriptional regulation of checkpoint genes on the tumour side of the immunological synapse. Heredity (Edinb). 2022;129(1):64-74.
Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350-1355.
Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol. 2022;19:254-267.
Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016;375(2):143-153.
Zhao J, Zhong S, Niu X, Jiang J, Zhang R, Li Q. The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy. Scand J Immunol. 2019;90:e12804.
Van der Touw W, Chen HM, Pan PY, Chen SH. LILRB receptor-mediated regulation of myeloid cell maturation and function. Cancer Immunol Immunother. 2017;66:1079-1087.
Zhang J, Mai S, Chen HM, Kang K, Li XC, Chen SH, et al. Leukocyte immunoglobulin-like receptors in human diseases: an overview of their distribution, function, and potential application for immunotherapies. J Leukoc Biol. 2017;102(2):351-360.
Eladl E, Tremblay-Lemay R, Rastgoo N, Musani R, Chen W, Liu A, et al. Role of CD47 in hematological malignancies. J Hematol Oncol. 2020;13:96.
Haddad Addad F, Daver N. Targeting CD47/sirpα in acute myeloid leukemia and myelodysplastic syndrome: preclinical and clinical developments of magrolimab. J Immunother Precis Oncol. 2021;4:67-71.
Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, et al. Defining ‘T cell exhaustion’. Nat Rev Immunol. 2019;19(11):665-674.
Carosella ED, Gregori S, Tronik-Le RD. HLA-G/LILRBs: a cancer immunotherapy challenge. Trends Cancer. 2021;7:389-392.
Nikiforow S, Alyea EP. Maximizing GVL in allogeneic transplantation: role of donor lymphocyte infusions. Hematology Am Soc Hematol Educ Program. 2014;2014(1):570-575.