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The Role of Stem Cell Transplant in the Therapy of Acute Myeloid Leukemia (AML)

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Acute Leukemias

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

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Abstract

Acute myeloid leukemia (AML) is the most common indication for allogeneic hematopoietic stem cell transplant (HSCT). Decision-making around allogeneic HSCT for AML patients in first remission should be based on the estimated risks of relapse and non-relapse mortality (NRM). Risk of relapse is most strongly informed by testing for cytogenetics, somatic mutations, and minimal residual disease (MRD) testing. Several risk scores based on the Hematopoietic Cell Transplant-Co-morbidity Index are available to estimate the risk of NRM using patient comorbidities, and these should be calculated prior to HSCT to inform decision-making. Conditioning chemotherapy should be individualized based on patient comorbidities. In younger fit patients, high-intensity or myeloablative conditioning is generally preferred to reduce relapse. In older (>65 years) patients or those with significant comorbid conditions, reduced intensity conditioning regimens are likely preferred. In vivo T-cell depletion with anti-thymocyte globulin and post-transplant cyclophosphamide reduces the risk of chronic graft-versus-host disease without a significant increase in risk of relapse. HLA-matched related relatives are preferred as donors although unrelated, haploidentical, and umbilical cord blood donors are all possible alternatives for patients without this option. Relapse remains a major problem following alloHSCT and use of chimerism monitoring and MRD testing can be used to inform treatments to prevent relapse including withdrawal of immunosuppression, donor lymphocyte infusion, and hypomethylating agents.

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References

  1. D’Souza A, Fretham, C (2018) Current uses and outcomes of hematopoietic stem cell transplantation – summary slides CIBMTR website 2018. Available from: https://www.cibmtr.org/Pages/index.aspx

  2. Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhauser M, Juliusson G, 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):579–90.

    Article  CAS  PubMed  Google Scholar 

  3. Appelbaum FR, Dahlberg S, Thomas ED, Buckner CD, Cheever MA, Clift RA, et al. Bone marrow transplantation or chemotherapy after remission induction for adults with acute nonlymphoblastic leukemia. A prospective comparison. Ann Intern Med. 1984;101(5):581–8.

    Article  CAS  PubMed  Google Scholar 

  4. Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, 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):2349–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schlenk RF, Dohner K, Krauter J, Frohling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358(18):1909–18.

    Article  CAS  PubMed  Google Scholar 

  6. Teira P, Battiwalla M, Ramanathan M, Barrett AJ, Ahn KW, Chen M, et al. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis. Blood. 2016;127(20):2427–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gerstung M, Papaemmanuil E, Martincorena I, Bullinger L, Gaidzik VI, Paschka P, et al. Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nat Genet. 2017;49(3):332–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378(13):1189–99.

    Article  CAS  PubMed  Google Scholar 

  9. Versluis J, Kalin B, Zeijlemaker W, Passweg J, Graux C, Manz MG, Vekemans MC, Biemond BJ, Legdeur M, van Marwijk Kooy M, de Weerdt O, Wijermans PW, Hoogendoorn M, Bargetzi MJ, Kuball J, Schouten HC, van der Velden V, Janssen J, Pabst T, Lowenberg B, Jongen-Lavrencic M, Schuurhuis G, Ossenkoppele G, Cornelissen JJ. Graft-versus-leukemia effect of allogeneic stem-cell transplantation and minimal residual disease in patients with acute myeloid leukemia in first complete remission. JCO Precis Oncol. 2017; https://doi.org/10.1200/PO.17.00078.

  10. Balsat M, Renneville A, Thomas X, de Botton S, Caillot D, Marceau A, et al. Postinduction minimal residual disease predicts outcome and benefit from allogeneic stem cell transplantation in acute myeloid leukemia with NPM1 mutation: a study by the Acute Leukemia French Association Group. J Clin Oncol. 2017;35(2):185–93.

    Article  CAS  PubMed  Google Scholar 

  11. Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, et al. Assessment of minimal residual disease in standard-risk AML. N Engl J Med. 2016;374(5):422–33.

    Article  CAS  PubMed  Google Scholar 

  12. Araki D, Wood BL, Othus M, Radich JP, Halpern AB, Zhou Y, 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):329–36.

    Article  PubMed  Google Scholar 

  13. Zhou Y, Othus M, Walter RB, Estey EH, Wu D, Wood BL. Deep NPM1 sequencing following allogeneic hematopoietic cell transplantation improves risk assessment in adults with NPM1-mutated AML. Biol Blood Marrow Transplant. 2018;24(8):1615–20.

    Article  CAS  PubMed  Google Scholar 

  14. Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005;23(9):1969–78.

    Article  PubMed  Google Scholar 

  15. Forman SJ, Rowe JM. The myth of the second remission of acute leukemia in the adult. Blood. 2013;121(7):1077–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ganzel C, Sun Z, Cripe LD, Fernandez HF, Douer D, Rowe JM, et al. Very poor long-term survival in past and more recent studies for relapsed AML patients: the ECOG-ACRIN experience. Am J Hematol. 2018;93:1074.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Burnett AK, Goldstone A, Hills RK, Milligan D, Prentice A, Yin J, et al. Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission. J Clin Oncol. 2013;31(10):1293–301.

    Article  PubMed  Google Scholar 

  18. Network NCC (2019) Acute myeloid leukemia (version 2.2019). Available from: https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf

  19. Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, et al. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015;16(9):1025–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gyurkocza B, Lazarus HM, Giralt S. Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission: potentially curative therapy. Bone Marrow Transplant. 2017;52(8):1083–90.

    Article  CAS  PubMed  Google Scholar 

  21. Nagler A, Savani BN, Labopin M, Polge E, Passweg J, Finke J, et al. Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. Lancet Haematol. 2015;2(9):e384–92.

    Article  PubMed  Google Scholar 

  22. Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28(23):3730–8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011;118(23):6037–42.

    Article  CAS  PubMed  Google Scholar 

  24. Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. UK Medical Research Council Adult and Children’s Leukaemia Working Parties. Lancet. 1998;351(9104):700–8.

    Article  CAS  PubMed  Google Scholar 

  25. Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med. 1995;332(4):217–23.

    Article  CAS  PubMed  Google Scholar 

  26. Gorin NC, Labopin M, Piemontese S, Arcese W, Santarone S, Huang H, et al. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis. Haematologica. 2015;100(4):558–64.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Keating A, DaSilva G, Perez WS, Gupta V, Cutler CS, Ballen KK, et al. Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research. Haematologica. 2013;98(2):185–92.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Saraceni F, Labopin M, Gorin NC, Blaise D, Tabrizi R, Volin L, et al. Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT. J Hematol Oncol. 2016;9(1):79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. The European Society for Blood and Marrow Transplantation (2017) EBMT annual report 2017. European Society for Blood and Marrow Transplantation. 1 Mar 2018

    Google Scholar 

  30. Lowenberg B, Voogt P. Autologous stem-cell transplantation and purging. J Clin Oncol. 1996;14(8):2194–6.

    Article  CAS  PubMed  Google Scholar 

  31. Cornelissen JJ, Versluis J, Passweg JR, van Putten WL, Manz MG, Maertens J, et al. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years. Leukemia. 2015;29(5):1041–50.

    Article  CAS  PubMed  Google Scholar 

  32. Limvorapitak W, Barnett MJ, Hogge DE, Forrest DL, Nevill TJ, Narayanan S, et al. Outcomes of intermediate risk karyotype acute myeloid leukemia in first remission undergoing autologous stem cell transplantation compared with allogeneic stem cell transplantation and chemotherapy consolidation: a retrospective, propensity-score adjusted analysis. Clin Lymphoma Myeloma Leuk. 2018;18(11):e481–e91.

    Article  PubMed  Google Scholar 

  33. Saraceni F, Bruno B, Lemoli RM, Meloni G, Arcese W, Falda M, et al. Autologous stem cell transplantation is still a valid option in good- and intermediate-risk AML: a GITMO survey on 809 patients autografted in first complete remission. Bone Marrow Transplant. 2017;52(1):163–6.

    Article  CAS  PubMed  Google Scholar 

  34. Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Venditti A, Piciocchi A, Candoni A, Melillo L, Calafiore V, Cairoli R, De Fabritiis P, Storti G, Salutari P, Lanza F, Martinelli G, Luppi M, Mazza, P, Falini B, Cuneo A, Specchia G, Fabbiano F, Tafuri A, Ronci B, Tieghi A, Fracchiolla N, Capelli D, Foà R, Ronco F, La Sala E, Fazi P, Maurillo L, Buccisano F, Del Principe M, Lo Coco F, Arcese W, Amadori S (2017) Risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukema: results of the AML 1310 trial of the GIMEMA group. iN: EHA annual meeting, 23 June 2017, Madrid

    Google Scholar 

  36. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sorror ML, Storb RF, Sandmaier BM, Maziarz RT, Pulsipher MA, Maris MB, et al. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol. 2014;32(29):3249–56.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Vaughn JE, Storer BE, Armand P, Raimondi R, Gibson C, Rambaldi A, et al. Design and validation of an augmented hematopoietic cell transplantation-comorbidity index comprising pretransplant ferritin, albumin, and platelet count for prediction of outcomes after allogeneic transplantation. Biol Blood Marrow Transplant. 2015;21(8):1418–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Elsawy M, Storer BE, Milano F, Sandmaier BM, Delaney C, Salit RB, et al. Prognostic performance of the augmented hematopoietic cell transplantation-specific comorbidity/age index in recipients of allogeneic hematopoietic stem cell transplantation from alternative graft sources. Biol Blood Marrow Transplant. 2019;25(5):1045–52.

    Article  PubMed  Google Scholar 

  40. Sorror ML, Sandmaier BM, Storer BE, Maris MB, Baron F, Maloney DG, et al. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol. 2007;25(27):4246–54.

    Article  PubMed  Google Scholar 

  41. Sorror ML. How I assess comorbidities before hematopoietic cell transplantation. Blood. 2013;121(15):2854–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kongtim P, Parmar S, Milton DR, Perez JMR, Rondon G, Chen J, et al. Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant. 2018;24:S107.

    Article  Google Scholar 

  43. Bejanyan N, Brunstein CG, Cao Q, Lazaryan A, Ustun C, Warlick ED, et al. Predictive value of disease risk comorbidity index for overall survival after allogeneic hematopoietic transplantation. Blood Adv. 2019;3(3):230–6.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lin RJ, Hilden PD, Elko TA, Dahi PB, Shahrokni A, Jakubowski AA, et al. Burden and impact of multifactorial geriatric syndromes in allogeneic hematopoietic cell transplantation for older adults. Blood Adv. 2019;3(1):12–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood. 2016;127(1):62–70.

    Article  CAS  PubMed  Google Scholar 

  46. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628–33.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Blaise D, Maraninchi D, Archimbaud E, Reiffers J, Devergie A, Jouet JP, et al. Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d’Etudes de la Greffe de Moelle Osseuse. Blood. 1992;79(10):2578–82.

    Article  CAS  PubMed  Google Scholar 

  48. Ringden O, Ruutu T, Remberger M, Nikoskelainen J, Volin L, Vindelov L, et al. A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. Blood. 1994;83(9):2723–30.

    Article  CAS  PubMed  Google Scholar 

  49. Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, et al. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013;122(24):3863–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Nagler A, Rocha V, Labopin M, Unal A, Ben Othman T, Campos A, et al. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen—a report from the acute leukemia working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013;31(28):3549–56.

    Article  CAS  PubMed  Google Scholar 

  51. Mitsuhashi K, Kako S, Shigematsu A, Atsuta Y, Doki N, Fukuda T, et al. Comparison of cyclophosphamide combined with total body irradiation, oral busulfan, or intravenous busulfan for allogeneic hematopoietic cell transplantation in adults with acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2016;22(12):2194–200.

    Article  CAS  PubMed  Google Scholar 

  52. Nagler A, Labopin M, Gorin NC, Ferrara F, Sanz MA, Wu D, et al. Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2014;99(8):1380–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Alatrash G, Kidwell KM, Thall PF, Di Stasi A, Chen J, Zope M, et al. Reduced intensity vs. myeloablative conditioning with fludarabine and PK-guided busulfan in allogeneic stem cell transplantation for patients with AML/MDS. Bone Marrow Transplant. 2018;54(8):1245–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, et al. Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chae YS, Sohn SK, Kim JG, Cho YY, Moon JH, Shin HJ, et al. New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Bone Marrow Transplant. 2007;40(6):541–7.

    Article  CAS  PubMed  Google Scholar 

  56. Liu H, Zhai X, Song Z, Sun J, Xiao Y, Nie D, et al. Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study. J Hematol Oncol. 2013;6:15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rambaldi A, Grassi A, Masciulli A, Boschini C, Mico MC, Busca A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015;16(15):1525–36.

    Article  CAS  PubMed  Google Scholar 

  58. Shimoni A, Labopin M, Savani B, Hamladji RM, Beelen D, Mufti G, et al. Intravenous busulfan compared with treosulfan-based conditioning for allogeneic stem cell transplantation in acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018;24(4):751–7.

    Article  CAS  PubMed  Google Scholar 

  59. Ringden O, Labopin M, Ehninger G, Niederwieser D, Olsson R, Basara N, et al. Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol. 2009;27(27):4570–7.

    Article  PubMed  Google Scholar 

  60. Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35(11):1154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, 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):1035–44.

    Article  PubMed  Google Scholar 

  62. Lioure B, Bene MC, Pigneux A, Huynh A, Chevallier P, Fegueux N, et al. Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study. Blood. 2012;119(12):2943–8.

    Article  CAS  PubMed  Google Scholar 

  63. Brands-Nijenhuis AV, Labopin M, Schouten HC, Volin L, Socie G, Cornelissen JJ, et al. Monosomal karyotype as an adverse prognostic factor in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem-cell transplantation in first complete remission: a retrospective survey on behalf of the ALWP of the EBMT. Haematologica. 2016;101(2):248–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ciurea SO, Labopin M, Socie G, Volin L, Passweg J, Chevallier P, et al. Relapse and survival after transplantation for complex karyotype acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and the University of Texas MD Anderson Cancer Center. Cancer. 2018;124(10):2134–41.

    Article  CAS  PubMed  Google Scholar 

  65. Poire X, Labopin M, Cornelissen JJ, Volin L, Richard Espiga C, Veelken JH, et al. Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year-old: a study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT). Am J Hematol. 2015;90(8):719–24.

    Article  PubMed  Google Scholar 

  66. Poire X, Labopin M, Maertens J, Yakoub-Agha I, Blaise D, Ifrah N, et al. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). J Hematol Oncol. 2017;10(1):20.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Solh MM, Solomon SR, Morris LE, Zhang X, Holland HK, Bashey A. The dilemma of conditioning intensity: when does myeloablative conditioning improve outcomes for allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25(3):606–12.

    Article  PubMed  Google Scholar 

  68. Bohl S, von Harsdorf S, Mulaw M, Hofmann S, Babiak A, Maier CP, et al. Strong impact of extramedullary involvement in high-risk AML patients with active disease receiving the FLAMSA conditioning regimen for HSCT. Bone Marrow Transplant. 2016;51(7):994–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Heinicke T, Labopin M, Schmid C, Polge E, Socie G, Blaise D, et al. Reduced relapse incidence with FLAMSA-RIC compared with busulfan/fludarabine for acute myelogenous leukemia patients in first or second complete remission: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018;24(11):2224–32.

    Article  CAS  PubMed  Google Scholar 

  70. Malard F, Labopin M, Stuhler G, Bittenbring J, Ganser A, Tischer J, et al. Sequential intensified conditioning regimen allogeneic hematopoietic stem cell transplantation in adult patients with intermediate- or high-risk acute myeloid leukemia in complete remission: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2017;23(2):278–84.

    Article  PubMed  Google Scholar 

  71. Saraceni F, Labopin M, Brecht A, Kroger N, Eder M, Tischer J, et al. Fludarabine-treosulfan compared to thiotepa-busulfan-fludarabine or FLAMSA as conditioning regimen for patients with primary refractory or relapsed acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). J Hematol Oncol. 2019;12(1):44.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ. 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):5675–87.

    Article  PubMed  Google Scholar 

  73. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367(16):1487–96.

    Article  CAS  PubMed  Google Scholar 

  74. Holtick U, Albrecht M, Chemnitz JM, Theurich S, Skoetz N, Scheid C, et al. Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults. Cochrane Database Syst Rev. 2014;(4):CD010189.

    Google Scholar 

  75. Ringden O, Labopin M, Bacigalupo A, Arcese W, Schaefer UW, Willemze R, et al. Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia. J Clin Oncol. 2002;20(24):4655–64.

    Article  CAS  PubMed  Google Scholar 

  76. Savani BN, Labopin M, Blaise D, Niederwieser D, Ciceri F, Ganser A, 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):256–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ringden O, Labopin M, Ciceri F, Velardi A, Bacigalupo A, Arcese W, et al. Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings? Leukemia. 2016;30(2):447–55.

    Article  CAS  PubMed  Google Scholar 

  78. Ruggeri A, Labopin M, Bacigalupo A, Gulbas Z, Koc Y, Blaise D, et al. Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide. Cancer. 2018;124(7):1428–37.

    Article  CAS  PubMed  Google Scholar 

  79. Salvatore D, Labopin M, Ruggeri A, Battipaglia G, Ghavamzadeh A, Ciceri F, et al. Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2018;103(8):1317–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med. 2016;375(10):944–53.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Eckfeldt CE, Randall N, Shanley RM, Yohe S, Bejanyan N, Dolan M, et al. Umbilical cord blood transplantation is a suitable option for consolidation of acute myeloid leukemia with FLT3-ITD. Haematologica. 2016;101(8):e348–51.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Sandhu KS, Brunstein C, DeFor T, Bejanyan N, Arora M, Warlick E, et al. Umbilical cord blood transplantation outcomes in acute myelogenous leukemia/myelodysplastic syndrome patients aged >/=70 years. Biol Blood Marrow Transplant. 2016;22(2):390–3.

    Article  PubMed  Google Scholar 

  83. Warlick ED, Peffault de Latour R, Shanley R, Robin M, Bejanyan N, Xhaard A, et al. Allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia: similar outcomes regardless of donor type. Biol Blood Marrow Transplant. 2015;21(2):357–63.

    Article  PubMed  Google Scholar 

  84. Weisdorf D, Eapen M, Ruggeri A, Zhang MJ, Zhong X, Brunstein C, et al. Alternative donor transplantation for older patients with acute myeloid leukemia in first complete remission: a center for international blood and marrow transplant research-eurocord analysis. Biol Blood Marrow Transplant. 2014;20(6):816–22.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Lee CJ, Savani BN, Mohty M, Labopin M, Ruggeri A, Schmid C, et al. Haploidentical hematopoietic cell transplantation for adult acute myeloid leukemia: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2017;102(11):1810–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001;98(10):2942–7.

    Article  CAS  PubMed  Google Scholar 

  87. Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10(9):855–64.

    Article  CAS  PubMed  Google Scholar 

  88. Kroger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med. 2016;374(1):43–53.

    Article  PubMed  CAS  Google Scholar 

  89. Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17(2):164–73.

    Article  CAS  PubMed  Google Scholar 

  90. Kanakry CG, Tsai HL, Bolanos-Meade J, Smith BD, Gojo I, Kanakry JA, et al. Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood. 2014;124(25):3817–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, et al. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010;115(16):3224–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Mielcarek M, Furlong T, O’Donnell PV, Storer BE, McCune JS, Storb R, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Rashidi A, Slade M, DiPersio JF, Westervelt P, Vij R, Romee R. Post-transplant high-dose cyclophosphamide after HLA-matched vs haploidentical hematopoietic cell transplantation for AML. Bone Marrow Transplant. 2016;51(12):1561–4.

    Article  CAS  PubMed  Google Scholar 

  94. Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018;11(1):40.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Locatelli F, Merli P, Pagliara D, Li Pira G, Falco M, Pende D, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after alphabeta T-cell and B-cell depletion. Blood. 2017;130(5):677–85.

    Article  CAS  PubMed  Google Scholar 

  96. D’Souza A, Fretham C (2018) Current uses and outcomes of hematopoietic cell transplantation (HCT): CIBMTR summary slides. Available from: https://www.cibmtr.org

  97. Boumber Y, Kantarjian H, Jorgensen J, Wen S, Faderl S, Castoro R, et al. A randomized study of decitabine versus conventional care for maintenance therapy in patients with acute myeloid leukemia in complete remission. Leukemia. 2012;26(11):2428–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G, 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):3361–9.

    Article  CAS  PubMed  Google Scholar 

  99. Choi J, Ritchey J, Prior JL, Holt M, Shannon WD, Deych E, et al. In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia. Blood. 2010;116(1):129–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Craddock C, Jilani N, Siddique S, Yap C, Khan J, Nagra S, et al. Tolerability and clinical activity of post-transplantation azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA trial. Biol Blood Marrow Transplant. 2016;22(2):385–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. de Lima M, Giralt S, Thall PF, de Padua SL, Jones RB, Komanduri K, et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 2010;116(23):5420–31.

    Article  PubMed  CAS  Google Scholar 

  102. de Lima M, Oran B, Champlin RE, Papadopoulos EB, Giralt SA, Scott BL, et al. CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes. Biol Blood Marrow Transplant. 2018;24(10):2017–24.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  103. Pusic I, Choi J, Fiala MA, Gao F, Holt M, Cashen AF, et al. Maintenance therapy with decitabine after allogeneic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2015;21(10):1761–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Brunner AM, Li S, Fathi AT, Wadleigh M, Ho VT, Collier K, et al. Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol. 2016;175(3):496–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Xuan L, Wang Y, Huang F, Jiang E, Deng L, Wu B, et al. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018;124(9):1954–63.

    Article  CAS  PubMed  Google Scholar 

  106. Burchert A, Bug G, Finke J, Stelljes M, Rollig C, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner E, Kroeger N, Wolschke C, Schleuning M, Elmaagacli A, Götze K, Schmid C, Jost E, Wolf D, Böhm A, Thiede C, Haferlach T, Bethge W, Harnisch S, Wittenberg M, Rospleszcz S, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder S (2018) Sorafenib as maintenance therapy post allogeneic stem cell transplantation for FLT3-ITD positive AML: results from the randomized, double-blind, placebo-controlled multicentre sormain trial. iN: ASH annual meeting, San Diego

    Google Scholar 

  107. Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A, et al. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia. 2012;26(3):381–9.

    Article  CAS  PubMed  Google Scholar 

  108. Wang Y, Wu DP, Liu QF, Qin YZ, Wang JB, Xu LP, et al. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood. 2014;124(12):1880–6.

    Article  CAS  PubMed  Google Scholar 

  109. Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, et al. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 2012;119(14):3256–62.

    Article  CAS  PubMed  Google Scholar 

  110. Clark JR, Scott SD, Jack AL, Lee H, Mason J, Carter GI, et al. Monitoring of chimerism following allogeneic haematopoietic stem cell transplantation (HSCT): technical recommendations for the use of short tandem repeat (STR) based techniques, on behalf of the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping Chimerism Working Group. Br J Haematol. 2015;168(1):26–37.

    Article  PubMed  Google Scholar 

  111. Hoffmann JC, Stabla K, Burchert A, Volkmann T, Bornhauser M, Thiede C, et al. Monitoring of acute myeloid leukemia patients after allogeneic stem cell transplantation employing semi-automated CD34+ donor cell chimerism analysis. Ann Hematol. 2014;93(2):279–85.

    Article  CAS  PubMed  Google Scholar 

  112. Huisman C, de Weger RA, de Vries L, Tilanus MG, Verdonck LF. Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia. Bone Marrow Transplant. 2007;39(5):285–91.

    Article  CAS  PubMed  Google Scholar 

  113. Lee HC, Saliba RM, Rondon G, Chen J, Charafeddine Y, Medeiros LJ, et al. Mixed T lymphocyte chimerism after allogeneic hematopoietic transplantation is predictive for relapse of acute myeloid leukemia and myelodysplastic syndromes. Biol Blood Marrow Transplant. 2015;21(11):1948–54.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol. 2005;23(9):1993–2003.

    Article  PubMed  Google Scholar 

  115. Wong E, Mason K, Collins J, Hockridge B, Boyd J, Gorelik A, et al. Prognostic limitations of donor T cell chimerism after myeloablative allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. Biol Blood Marrow Transplant. 2017;23(5):840–4.

    Article  CAS  PubMed  Google Scholar 

  116. Rettinger E, Willasch AM, Kreyenberg H, Borkhardt A, Holter W, Kremens B, et al. Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation. Blood. 2011;118(20):5681–8.

    Article  CAS  PubMed  Google Scholar 

  117. Shayegi N, Kramer M, Bornhauser M, Schaich M, Schetelig J, Platzbecker U, 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.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Leukemia/Bone Marrow Transplant Program of British Columbia (BC), BC Cancer, The University of British Columbia, Vancouver, BC, Canada

    David Sanford & Florian Kuchenbauer

  2. Division of Hematology, Dalhousie University, Halifax, NS, Canada

    Mahmoud Elsawy

  3. Clinical Research Division, Fred Hutchinson Cancer Research Centre, Seattle, WA, USA

    Mahmoud Elsawy

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  1. David Sanford
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  3. Florian Kuchenbauer
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Correspondence to David Sanford .

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    Stefan H. Faderl

  2. Department of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Hagop M. Kantarjian

  3. Clinical Research Division, Fred Hutch, Seattle, WA, USA

    Elihu Estey

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Sanford, D., Elsawy, M., Kuchenbauer, F. (2021). The Role of Stem Cell Transplant in the Therapy of Acute Myeloid Leukemia (AML). In: Faderl, S.H., Kantarjian, H.M., Estey, E. (eds) Acute Leukemias. Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-53633-6_7

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