Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The evolving concept of indications for allogeneic hematopoietic cell transplantation during first complete remission of acute myeloid leukemia

Bone Marrow Transplantation volume 56, pages 1257–1265 (2021)Cite this article

Subjects

Abstract

The long-standing debate of whether patients with acute myeloid leukemia (AML) should proceed to allogeneic hematopoietic cell transplantation (HCT) during first complete remission (CR1) remains unsettled. Although allogeneic HCT during CR1 used to be recommended for those with intermediate or poor cytogenetics if they had a matched sibling donor, the concept of indications for allogeneic HCT during CR1 has been evolving by virtue of advances in understanding of the molecular pathogenesis of AML and innovations in transplantation practice attained over the last few decades. The incorporation of molecular profiles of leukemia has been shown to contribute to further refinements of risk classification that had previously relied mostly on cytogenetics, while the progress in transplantation procedures has made it possible to perform transplantations more safely even for patients without a matched sibling donor. These significant changes have underpinned the need to reappraise indications for allogeneic HCT during CR1 of AML. Improvements in clinical applications of genetic and measurable residual disease information as well as in transplantation technology are expected to further refine indications for allogeneic HCT during CR1, and thus promote an individualized approach for the treatment of AML.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Yanada M, Takami A, Yamasaki S, Arai Y, Konuma T, Uchida N, et al. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia conducted in Japan during the past quarter century. Ann Hematol. 2020;99:1351–60.

    Article  PubMed  Google Scholar 

  2. 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;332:217–23.

    Article  CAS  PubMed  Google Scholar 

  3. Keating S, de Witte T, Suciu S, Willemze R, Hayat M, Labar B, et al. The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA. European Organization for Research and Treatment of Cancer. Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto. Br J Haematol. 1998;102:1344–53.

    Article  CAS  PubMed  Google Scholar 

  4. Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96:4075–83.

    Article  CAS  PubMed  Google Scholar 

  5. Burnett AK, Wheatley K, Goldstone AH, Stevens RF, Hann IM, Rees JH, et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol. 2002;118:385–400.

    Article  PubMed  Google Scholar 

  6. Suciu S, Mandelli F, de Witte T, Zittoun R, Gallo E, Labar B, et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood. 2003;102:1232–40.

    Article  CAS  PubMed  Google Scholar 

  7. Schlenk RF, Benner A, Hartmann F, del Valle F, Weber C, Pralle H, et al. Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial. Leukemia 2003;17:1521–8.

    Article  CAS  PubMed  Google Scholar 

  8. Jourdan E, Boiron JM, Dastugue N, Vey N, Marit G, Rigal-Huguet F, et al. Early allogeneic stem-cell transplantation for young adults with acute myeloblastic leukemia in first complete remission: an intent-to-treat long-term analysis of the BGMT experience. J Clin Oncol. 2005;23:7676–84.

    Article  PubMed  Google Scholar 

  9. Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM, et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007;109:3658–66.

    Article  CAS  PubMed  Google Scholar 

  10. Basara N, Schulze A, Wedding U, Mohren M, Gerhardt A, Junghanss C, et al. Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission. Leukemia. 2009;23:635–40.

    Article  CAS  PubMed  Google Scholar 

  11. Sakamaki H, Miyawaki S, Ohtake S, Emi N, Yagasaki F, Mitani K, et al. Allogeneic stem cell transplantation versus chemotherapy as post-remission therapy for intermediate or poor risk adult acute myeloid leukemia: results of the JALSG AML97 study. Int J Hematol. 2010;91:284–92.

    Article  PubMed  Google Scholar 

  12. Yanada M, Matsuo K, Emi N, Naoe T. Efficacy of allogeneic hematopoietic stem cell transplantation depends on cytogenetic risk for acute myeloid leukemia in first disease remission: a metaanalysis. Cancer 2005;103:1652–8.

    Article  PubMed  Google Scholar 

  13. 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;301:2349–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kekre N, Antin JH. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood. 2014;124:334–43.

    Article  CAS  PubMed  Google Scholar 

  15. Yanada M. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia during first complete remission: a clinical perspective. Int J Hematol. 2015;101:243–54.

    Article  CAS  PubMed  Google Scholar 

  16. Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2016;127:29–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 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;129:424–47.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 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;9:579–90.

    Article  CAS  PubMed  Google Scholar 

  19. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325–36.

    Article  CAS  PubMed  Google Scholar 

  20. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116:354–65.

    Article  CAS  PubMed  Google Scholar 

  21. Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93:3074–80.

    CAS  PubMed  Google Scholar 

  22. Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, 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;98:1752–9.

    Article  CAS  PubMed  Google Scholar 

  23. Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001;97:2434–9.

    Article  CAS  PubMed  Google Scholar 

  24. Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99:4326–35.

    Article  CAS  PubMed  Google Scholar 

  25. Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100:59–66.

    Article  CAS  PubMed  Google Scholar 

  26. Boissel N, Cayuela JM, Preudhomme C, Thomas X, Grardel N, Fund X, et al. Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy. Leukemia. 2002;16:1699–704.

    Article  CAS  PubMed  Google Scholar 

  27. Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–66.

    Article  CAS  PubMed  Google Scholar 

  28. Schnittger S, Schoch C, Kern W, Mecucci C, Tschulik C, Martelli MF, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood. 2005;106:3733–9.

    Article  CAS  PubMed  Google Scholar 

  29. Dohner K, Schlenk RF, Habdank M, Scholl C, Rucker FG, Corbacioglu A, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106:3740–6.

    Article  PubMed  Google Scholar 

  30. Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, et al. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood. 2006;107:4011–20.

    Article  CAS  PubMed  Google Scholar 

  31. Marcucci G, Maharry K, Radmacher MD, Mrozek K, Vukosavljevic T, Paschka P, et al. Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B Study. J Clin Oncol. 2008;26:5078–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wouters BJ, Lowenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113:3088–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.

    Article  PubMed  Google Scholar 

  34. Breems DA, Van Putten WL, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KB, Mellink CH, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26:4791–7.

    Article  PubMed  Google Scholar 

  35. Medeiros BC, Othus M, Fang M, Roulston D, Appelbaum FR. Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. Blood. 2010;116:2224–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yanada M, Kurosawa S, Yamaguchi T, Yamashita T, Moriuchi Y, Ago H, et al. Prognosis of acute myeloid leukemia harboring monosomal karyotype in patients treated with or without allogeneic hematopoietic cell transplantation after achieving complete remission. Haematologica. 2012;97:915–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kayser S, Zucknick M, Dohner K, Krauter J, Kohne CH, Horst HA, et al. Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood 2012;119:551–8.

    Article  CAS  PubMed  Google Scholar 

  38. Herold T, Rothenberg-Thurley M, Grunwald VV, Janke H, Goerlich D, Sauerland MC, et al. Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia. Leukemia. 2020;34:3161–72.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Harada Y, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, et al. Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study. Leuk Res. 2018;66:20–27.

    Article  PubMed  Google Scholar 

  40. Sakaguchi M, Yamaguchi H, Najima Y, Usuki K, Ueki T, Oh I, et al. Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia. Blood Adv. 2018;2:2744–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Boddu PC, Kadia TM, Garcia-Manero G, Cortes J, Alfayez M, Borthakur G, et al. Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes. Cancer. 2019;125:1091–100.

    Article  CAS  PubMed  Google Scholar 

  42. Döhner K, Thiede C, Jahn N, Panina E, Gambietz A, Larson RA, et al. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood 2020;135:371–80.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Eisfeld AK, Kohlschmidt J, Mims A, Nicolet D, Walker CJ, Blachly JS, et al. Additional gene mutations may refine the 2017 European LeukemiaNet classification in adult patients with de novo acute myeloid leukemia aged <60 years. Leukemia. 2020;34:3215–27.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Armand P, Kim HT, Zhang MJ, Perez WS, Dal Cin PS, Klumpp TR, et al. Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transplant. 2012;18:280–8.

    Article  PubMed  Google Scholar 

  45. Yanada M, Mori J, Aoki J, Harada K, Mizuno S, Uchida N, et al. Effect of cytogenetic risk status on outcomes for patients with acute myeloid leukemia undergoing various types of allogeneic hematopoietic cell transplantation: an analysis of 7812 patients. Leuk Lymphoma. 2018;59:601–09.

    Article  PubMed  Google Scholar 

  46. Schmid C, Labopin M, Socie G, Daguindau E, Volin L, Huynh A, et al. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation. Blood. 2015;126:2062–9.

    Article  CAS  PubMed  Google Scholar 

  47. Deol A, Sengsayadeth S, Ahn KW, Wang HL, Aljurf M, Antin JH, et al. Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis. Cancer. 2016;122:3005–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Canaani J, Labopin M, Itala-Remes M, Blaise D, Socie G, Forcade E, et al. Prognostic significance of recurring chromosomal abnormalities in transplanted patients with acute myeloid leukemia. Leukemia. 2019;33:1944–52.

    Article  CAS  PubMed  Google Scholar 

  49. Grimm J, Jentzsch M, Bill M, Goldmann K, Schulz J, Niederwieser D, et al. Prognostic impact of the ELN2017 risk classification in patients with AML receiving allogeneic transplantation. Blood Adv. 2020;4:3864–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet. 1998;352:1087–92.

    Article  CAS  PubMed  Google Scholar 

  51. 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;106:2912–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Barba P, Martino R, Perez-Simon JA, Fernandez-Aviles F, Castillo N, Pinana JL, et al. Combination of the Hematopoietic Cell Transplantation Comorbidity Index and the European Group for Blood and Marrow Transplantation score allows a better stratification of high-risk patients undergoing reduced-toxicity allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20:66–72.

    Article  PubMed  Google Scholar 

  53. 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;32:3249–56.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Versluis J, Labopin M, Niederwieser D, Socie G, Schlenk RF, Milpied N, et al. Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission. Leukemia. 2015;29:51–7.

    Article  CAS  PubMed  Google Scholar 

  55. 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. 2019;54:839–48.

    Article  CAS  PubMed  Google Scholar 

  56. Shouval R, Fein JA, Shouval A, Danylesko I, Shem-Tov N, Zlotnik M, et al. External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019;3:1881–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yanada M, Konuma T, Mizuno S, Saburi M, Shinohara A, Tanaka M, et al. Predicting non-relapse mortality following allogeneic hematopoietic cell transplantation during first remission of acute myeloid leukemia. Bone Marrow Transplant. 2021;56:387–94.

    Article  PubMed  Google Scholar 

  58. 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;358:1909–18.

    Article  CAS  PubMed  Google Scholar 

  59. Cornelissen JJ, Breems D, van Putten WL, Gratwohl AA, Passweg JR, Pabst T, et al. Comparative analysis of the value of allogeneic hematopoietic stem-cell transplantation in acute myeloid leukemia with monosomal karyotype versus other cytogenetic risk categories. J Clin Oncol. 2012;30:2140–6.

    Article  PubMed  Google Scholar 

  60. Rollig C, Bornhauser M, Kramer M, Thiede C, Ho AD, Kramer A, et al. Allogeneic stem-cell transplantation in patients with NPM1-mutated acute myeloid leukemia: results from a prospective donor versus no-donor analysis of patients after upfront HLA typing within the SAL-AML 2003 trial. J Clin Oncol. 2015;33:403–10.

    Article  CAS  PubMed  Google Scholar 

  61. Kurosawa S, Yamaguchi H, Yamaguchi T, Fukunaga K, Yui S, Wakita S, et al. Decision analysis of postremission therapy in cytogenetically intermediate-risk acute myeloid leukemia: the impact of FLT3 internal tandem duplication, nucleophosmin, and CCAAT/enhancer binding protein alpha. Biol Blood Marrow Transplant. 2016;22:1125–32.

    Article  CAS  PubMed  Google Scholar 

  62. Versluis J, In ‘t Hout FE, Devillier R, van Putten WL, Manz MG, Vekemans MC, et al. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio. Leukemia. 2017;31:26–33.

    Article  CAS  PubMed  Google Scholar 

  63. Heidrich K, Thiede C, Schäfer-Eckart K, Schmitz N, Aulitzky WE, Krämer A, et al. Allogeneic hematopoietic cell transplantation in intermediate risk acute myeloid leukemia negative for FLT3-ITD, NPM1- or biallelic CEBPA mutations. Ann Oncol. 2017;28:2793–98.

    Article  CAS  PubMed  Google Scholar 

  64. Baron F, Stevens-Kroef M, Kicinski M, Meloni G, Muus P, Marie JP, et al. Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype. Haematologica. 2019;104:1168–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Terwijn M, van Putten WL, Kelder A, van der Velden VH, Brooimans RA, Pabst T, et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol. 2013;31:3889–97.

    Article  PubMed  Google Scholar 

  66. Freeman SD, Virgo P, Couzens S, Grimwade D, Russell N, Hills RK, et al. Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia. J Clin Oncol. 2013;31:4123–31.

    Article  PubMed  Google Scholar 

  67. Hubmann M, Köhnke T, Hoster E, Schneider S, Dufour A, Zellmeier E, et al. Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies those at high risk of relapse. Haematologica. 2014;99:1317–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Klco JM, Miller CA, Griffith M, Petti A, Spencer DH, Ketkar-Kulkarni S, et al. Association between mutation clearance after induction therapy and outcomes in acute myeloid leukemia. JAMA 2015;314:811–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 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;374:422–33.

    Article  CAS  PubMed  Google Scholar 

  70. 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;35:185–93.

    Article  CAS  PubMed  Google Scholar 

  71. Freeman SD, Hills RK, Virgo P, Khan N, Couzens S, Dillon R, et al. Measurable residual disease at induction redefines partial response in acute myeloid leukemia and stratifies outcomes in patients at standard risk without NPM1 mutations. J Clin Oncol. 2018;36:1486–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 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;378:1189–99.

    Article  CAS  PubMed  Google Scholar 

  73. Morita K, Kantarjian HM, Wang F, Yan Y, Bueso-Ramos C, Sasaki K, et al. Clearance of somatic mutations at remission and the risk of relapse in acute myeloid leukemia. J Clin Oncol. 2018;36:1788–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Venditti A, Piciocchi A, Candoni A, Melillo L, Calafiore V, Cairoli R, et al. GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood. 2019;134:935–45.

    Article  CAS  PubMed  Google Scholar 

  75. Short NJ, Ravandi F. How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia? Haematologica. 2019;104:1532–41.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Bezerra MF, Lima AS, Piqué-Borràs MR, Silveira DR, Coelho-Silva JL, Pereira-Martins DA, et al. Co-occurrence of DNMT3A, NPM1, FLT3 mutations identifies a subset of acute myeloid leukemia with adverse prognosis. Blood. 2020;135:870–75.

    Article  PubMed  Google Scholar 

  77. Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617–29.

    Article  CAS  PubMed  Google Scholar 

  80. Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood 2020;135:2137–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017.

  82. Stein EM, DiNardo CD, Fathi AT, Mims AS, Pratz KW, Savona MR, et al. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study. Blood. 2020.

  83. Fenwarth L, Thomas X, de Botton S, Duployez N, Bourhis JH, Lesieur A, et al. A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia. Blood. 2020.

Download references

Acknowledgements

This work was supported in part by a grant from the Aichi Cancer Research Foundation, grant number: 2020-1-11.

Author information

Authors and Affiliations

  1. Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan

    Masamitsu Yanada

Authors
  1. Masamitsu Yanada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masamitsu Yanada.

Ethics declarations

Conflict of interest

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yanada, M. The evolving concept of indications for allogeneic hematopoietic cell transplantation during first complete remission of acute myeloid leukemia. Bone Marrow Transplant 56, 1257–1265 (2021). https://doi.org/10.1038/s41409-021-01247-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-021-01247-4

This article is cited by

Search

Advanced search

Quick links