Autologous hematopoietic stem cell transplantation in acute myeloid leukemia

With the advances of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the role of autologous hematopoietic stem cell transplantations (ASCT) in patients with acute myeloid leukemia (AML) have diminished.1 However, for certain types of patients ASCT has resulted in improved clinical outcomes,2 with relatively low relapse rates and very low non-relapse mortality (NRM). ASCT also has comparable overall survival to allo-HSCT in some patients.

Yuanqi Zhao, from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, CN, and colleagues, discussed the indications for ASCT therapy in patients with AML, looking at literature and clinical trials to evaluate clinical outcomes.3

ASCT versus intensive chemotherapy
  • Standard chemotherapy induces morphological CR for AML, but relapse is a common cause of poor long-term survival
  • Clinical outcomes were compared using 381 patients with AML in CR14:
    • ASCT substantially reduced the relapse risk (RR) in all patients compared with those who did not receive ASCT
    • Seven-year leukemia free survival (LFS): 53% vs 40%, P = 0.04
    • For patients over 65, progression-free survival (PFS) and overall survival (OS) were significantly better in patients receiving ASCT than those not receiving the therapy
  • A retrospective study5 comparing ASCT (n = 152) and chemotherapy (n = 271) in patients with CR1 status AML found that:
    • Both 5-year OS (54% vs 40%, P = 0.02), and LFS (44% vs 30%, P < 0.001) were better in patients after ASCT compared with patients receiving chemotherapy
    • No significant difference identified in NRM

These studies suggest that ASCT is safe, with an acceptable safety profile, and is associated with low RRs and better LFS than chemotherapy alone. As data to support this came from retrospective trials, additional prospective studies would be needed to determine if this approach could lead to improve OS.

ASCT versus allo-HSCT

Stem cell transplantation is an important therapy for AML, and includes ASCT and allo-HSCT from both matched-sibling donors (MSDs) and matched unrelated donors (MUDs). MSD-allo-SCT is the best choice for patients with AML who are considering transplantation.6 Despite this, ASCT can achieve comparable results to those of MSD-allo-SCT in some patients, and for intermediate-risk patients, is associated with better survival when compared with MUD-allo-SCT or mismatched sibling donor transplantation.


Study type

Patient status






Cornelissen et al5


Intermediate-risk, CR1

Allo-SCT vs ASCT

60% vs 54%, P > 0.05




Zittoun et al7



MSD-allo-SCT vs ASCT vs CBT


4-year: 55% vs 48% vs 30%



Yao et al8



ASCT vs MSD-allo-SCT

73.6% vs 74.6%, P = 0.616

69.1% vs 73.6%, P = 0.559

4.3% vs 11.2%, P = 0.215

26.6%  vs 14.1%, P = 0.083

Keating et al9



MSD-allo-SCT vs ASCT

61% vs 54%, P = 0.19

58% vs 47%, P = 0.13



Mizutani et al10




66% vs 64%, P = 0.83

64% vs 58%, P = 0.16

7% vs 17%, P = 0.005


Gorin et al11



ASCT vs MUD-allo-SCT

83% vs 62%, P = 0.008

67% vs 64%, P > 0.05

3.7% vs 19%, P < 0.000

29% vs 17%, P < 0.0001

Chevallier et al12




59% vs 50%, P = 0.45

57% vs 46%, P = 0.37



Gorin et al13



ASCT vs haploSCT

64% vs 57%, P = 0.12

47% vs 48%, P = 0.73

4% vs 25%, P < 0.00001

50% vs 27%, P < 0.00001


Chen et al14



ASCT vs haploSCT

79.0% vs 80.1%, P = 0.769

66.1% vs 77.4%, P = 0.079



Table 1: Comparison of ASCT versus allo-SCT in patients with AML. Prosp, prospective study; retro, retrospective study; DFS, disease-free survival; haploSCT, haploidentical transplantation; MUD-BMT, allogeneic bone marrow transplantation from a matched-unrelated donor; CBT, cord blood allo-SCT

Prognostic factors for ASCT in AML
  • In most studies, age >50 years was demonstrated to be an independent prognosis factor for poor survival in patients with AML who underwent autografting2
  • However, in some studies age did not significantly impact outcome following ASCT in some studies14—16
  • As age seems to be an unreliable prognostic factor, tolerance of induction treatment, cytogenetic risks and performance status should be taken into consideration
Cytogenetic and molecular risk stratification

Cytogenetic risk stratification is a crucial predictor for clinical outcomes in patients with AML after ASCT. Favourable-risk patients benefited more from ASCT compared allo-HSCT, and intermediate-risk patients showed similar outcomes to patients in the allo-SCT arm.11 ASCT may be a feasible treatment for patients with AML who are in CR1 – predominantly for those with favourable- and intermediate-risk molecular cytogenetics.

  • A phase II study of arsenic trioxide (ATO) prior to ASCT in relapse APL found:17
  • Five-year event-free survival (EFS) 65%
  • Five-year OS 77%
  • ASCT was efficacious and feasible for patients with relapsed APL in CR2
  • OS after ASCT in patients with relapsed APL was better than in those patient who received chemotherapy and ATO18
  • ASCT may be better than allo-SCT for patients with APL in CR219
  • ASCT is an effective post-remission therapy for patients with APL in CR2
AML with t(8;21) or inv(16) calligraphy
  • Five-year OS in patients with AML carrying t(8;21) with isolated y chromosome following ASCT was 88.8%20
  • ASCT was associated with a lower treatment related mortality (TRM) and a similar LFS to patients with inv(16) or t(8;21) receiving allo-SCT21
  • Patients with AML with double mutant CCAAT enhancer binding protein alpha (CEBPA) treated with ASCT and allo-SCT were compared with those treated with chemotherapy,22 identifying that ASCT and allo-SCT were associated with better LFS
AML with FLT3/ITD mutation
  • Both ASCT and allo-SCT were associated with lower RR, and better DFS and OS than treatment with chemotherapy alone, however, there was no difference between OS and DFS between allo-SCT and ASCT23
MRD status pre-ASCT

Minimal residual disease (MRD) is crucial when distinguishing whether patients with AML are eligible for ASCT, with multiparameter flow cytometry (MFC) and quantitative polymerase chain reaction (qPCR) being used to monitor MRD before and after ASCT. MRD status is seen as an independent prognostic factor for both OS and RFS after ASCT, which is a promising therapy for patients with negative MRD pre-ASCT.24

CD34+ cell count in ASCT

Studies have shown that clinical outcomes are significantly affected by CD34+ cell counts, with low CD34+ cell counts negatively affecting engraftment, and higher CD34+ cell counts being associated with higher RRs.25


ASCT is recommended for patients in first complete remission (CR1) with favourable and intermediate-risk AML and CR2 in patients with acute promyelocytic leukemia (APL), when a matched sibling donor is not available. Prior to ASCT, MRD status is the most important factor, and can be used to effectively predict outcomes after ASCT. Age should not be a limiting factor for conducting ASCT. Current conditioning regimens seem to favour the use of busulfan due to its high antileukemic effect and good safety profile.

Further studies are necessary to investigate the impact of molecular-targeted therapeutic drugs, along with more prospective trials on difference conditioning regimens in patients with varying molecular cytogenetics.

  1. Bertoli S, et al. Improved outcome for AML patients over the years 2000–2014. Blood cancer journal. 2017 Nov 29. 7(12):635.
  2. Saraceni F, 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 transplantation. 2017 Jan. 52(1):163.
  3. Zhao Y, et al. Autologous hematopoietic stem cell transplantation in acute myeloid leukemia. Biol of Blood Marrow Transplant. 2019 May 3.
  4. Burnett AK, 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. The Lancet. 1998 Mar 7. 351(9104):700-8.
  5. Cornelissen JJ, et al. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years. Leukemia. 2015 May. 29(5):1041.
  6. Limvorapitak W, 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. Clinical Lymphoma Myeloma and Leukemia. 2018 Nov 1. 18(11):e481-91.
  7. Zittoun RA, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. New England Journal of Medicine. 1995 Jan 26. 332(4):217-23.
  8. Yao J, et al. Combination of cytogenetic classification and MRD status correlates with outcome of autologous versus allogeneic stem cell transplantation in adults with primary acute myeloid leukemia in first remission. Leukemia research. 2017 Apr 1. 55:97-104.
  9. Keating A, 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 Feb 1. 98(2):185-92.
  10. Mizutani M, et al. Comparison of autologous and unrelated transplants for cytogenetically normal acute myelogenous leukemia. Biology of Blood and Marrow Transplantation. 2017 Sep 1. 23(9):1447-54.
  11. Gorin NC, et al. Unrelated matched versus autologous transplantation in adult patients with good and intermediate risk acute myelogenous leukemia in first molecular remission. American journal of hematology. 2017 Dec. 92(12):1318-23.
  12. Chevallier P, et al. Comparison of umbilical cord blood allogeneic stem cell transplantation vs. auto‐SCT for adult acute myeloid leukemia patients in second complete remission at transplant: a retrospective study on behalf of the SFGM‐ European journal of haematology. 2015 May. 94(5):449-55.
  13. Gorin NC, et al. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis. Haematologica. 2015 Apr 1. 100(4):558-64.
  14. Chen J, et al. Comparison of Autologous Stem Cell Transplantation versus Haploidentical Donor Stem Cell Transplantation for Favorable-and Intermediate-Risk Acute Myeloid Leukemia Patients in First Complete Remission. Biology of Blood and Marrow Transplantation. 2018 Apr 1. 24(4):779-88.
  15. Heini AD, et al. Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years. Leukemia research. 2017 Feb 1. 53:28-34.
  16. Huang H, et al. Modified BuCy is an alternative conditioning regimen for lymphoma patients undergoing autologous stem cell transplantation. Annals of hematology. 2019 Jan 12:1-8.
  17. Yanada M, et al. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18. 121(16):3095-102.
  18. Lengfelder E, et al. Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet. Leukemia. 2015 May. 29(5):1084.
  19. Chakrabarty JL, et al. Autologous is superior to allogeneic hematopoietic cell transplantation for acute promyelocytic leukemia in second complete remission. Biology of Blood and Marrow Transplantation. 2014 Jul 1. 20(7):1021-5.
  20. Yoon JH, et al. Comparison of the effects of early intensified induction chemotherapy and standard 3+ 7 chemotherapy in adult patients with acute myeloid leukemia. Blood research. 2017 Sep 1. 52(3):174-83.
  21. Gorin NC, et al. Identical outcome after autologous or allogeneic genoidentical hematopoietic stem-cell transplantation in first remission of acute myelocytic leukemia carrying inversion 16 or t(8; 21): a retrospective study from the European Cooperative Group for Blood and Marrow Transplantation. Journal of Clinical Oncology. 2008 Jul 1. 26(19):3183-8.
  22. Schlenk RF, et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood. 2013 Aug 29. 122(9):1576-82.
  23. Ma Y, et al. Is allogeneic transplantation really the best treatment for FLT 3/ITD‐positive acute myeloid leukemia? A systematic review. Clinical transplantation. 2015 Feb. 29(2):149-60.
  24. Mulé MP, et al. Multigene measurable residual disease assessment improves acute myeloid leukemia relapse risk stratification in autologous hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation. 2016 Nov 1. 22(11):1974-82.
  25. Gorin NC, et al. Higher incidence of relapse in patients with acute myelocytic leukemia infused with higher doses of CD34+ cells from leukapheresis products autografted during the first remission. Blood. 2010 Oct 28. 116(17):3157-62.
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