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.

  • Letter to the Editor
  • Published:

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 volume 52, pages 163–166 (2017)Cite this article

Subjects

Post-remission strategy for acute myeloid leukemia (AML) is matter of intense debate. The currently available options are represented by intensive standard chemotherapy, autologous (auto-HSCT) and allogeneic stem cell transplantation (allo-HSCT). Allo-HSCT is the most effective treatment to prevent leukemia relapse; however, it is associated with high non-relapse mortality (NRM) rates and risk of developing GvHD. Auto-HSCT is an alternative approach, able to provide an acceptable long-term outcome with lower NRM rates and better quality of life for survivors, compared with allo-HSCT.1 However, there are concerns about high relapse incidence, due to the lack of GvL effect and the possibility of graft contamination by leukemic stem cells, which could potentially contribute to relapse. Several randomized trials and meta-analyses have reported better leukemia-free survival (LFS) following auto-HSCT compared with conventional chemotherapy,2 while recent studies3, 4, 5, 6 failed to show a significant difference in overall survival (OS) between auto- and allo-HSCT. We herein report the results of a retrospective analysis performed on a large homogeneous cohort of AML patients autografted in first complete remission (CR1). We included 809 consecutive AML patients receiving auto-HSCT in CR1 in 72 GITMO centers between 1985 and 2008; patients having M3 AML were excluded. Median age at transplant was 47 years (range 16–75), while median year of transplant was 2001 (range 1985–2008). All patients were evaluable for cytogenetic data. Cytogenetic risk categories were defined as follows: i—good risk group, including patients bearing t(8;21)(q22;q22), inv(16)(p13q22)/t(16;16)(p13;q22) or normal karyotype with mutant NPM1 and wild type FLT3-ITD; ii—poor risk group, including patients bearing complex karyotype, inv(3)(q21q26)/t(3;3)(q21;q26)−5,-5q,−7,-7q, other 11q23 abn, inv(3)(q21q26.2), t(3;3)(q21q26.2), t(6;9), t(9;22), abn(17p), or normal karyotype in the presence of FLT3-ITD; iii—intermediate risk group, including patients with cytogenetics abnormalities not encompassed in good or poor risk group in the absence of NPM1 mutation or FLT3-ITD. Cytogenetic risk was good, intermediate and poor in 131 (16%), 544 (67%) and 134 (17%) of patients, respectively. NPM and FLT3 mutational status was available in 170 (39%) of patients with normal karyotype, who were accordingly included in good risk (NPM+/FLT3−), poor risk (FLT3+) or intermediate risk (NPM−/FLT3−), respectively. Two hundred and seventy patients bearing normal karyotype were unavailable for molecular evaluation, and were therefore included in the intermediate risk category. Median interval from diagnosis to transplant was 171 days (range 14–9451); conditioning regimen was chemotherapy busulphan-based, chemotherapy not busulphan-based and TBI-based in 56%, 30% and 9% of patients, respectively; in 37 patients the conditioning regimen was unknown. Stem cell source was bone marrow (BM) or peripheral blood stem cells (PBSCs) in 32% and 68% of patients respectively. The characteristics of the patients are summarized in Table 1.

Table 1 Characteristics of patients
Full size table

Survival curves were estimated by the Kaplan–Meier method, and the log-rank test was used for univariate comparisons. Cumulative incidence curves were used for relapse incidence and non-relapse mortality in a competing risks setting, where the risks of death in CR and relapse were considered as competing risks; the Gray test was used for univariate comparisons. Assessments of potential risk factors for outcomes of interest were evaluated in multivariate analyses using the Cox proportional hazards model. The variables considered in the multivariate analysis were stem cell source, cytogenetic risk, age, interval from diagnosis to transplant, year of transplant and kind of conditioning regimen. The type I error rate was fixed at 0.05 for the determination of factors associated with time-to-event outcomes; all tests were two-sided.

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

Relevant articles

Open Access articles citing this article.

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

Figure 1

References

  1. Messerer D, Engel J, Hasford J, Schaich M, Ehninger G, Sauerland C et al. Impact of different post-remission strategies on quality of life in patients with acute myeloid leukemia. Haematologica 2008; 93: 826–833.

    Article  Google Scholar 

  2. 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: 6037–6042.

    Article  CAS  Google Scholar 

  3. 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: 185–192.

    Article  Google Scholar 

  4. Cornelissen JJ, Versluis J, Passweg JR, van Putten WLJ, Manz MG, Maertens MG et al. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years. Leukemia 2015; 29: 1041–1050.

    Article  CAS  Google Scholar 

  5. 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: 558–564.

    Article  Google Scholar 

  6. Mizutani M, Hara M, Fujita H, Aoki J, Kanamori H, Ohashi K et al. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR. Bone Marrow Transplant 2016; 51: 645–653.

    Article  CAS  Google Scholar 

  7. Gorin NC, Najman A, Duhamel G . Autologous bone-marrow transplantation in acute myelocytic leukaemia. Lancet 1977; 1: 1050.

    Article  CAS  Google Scholar 

  8. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 2007; 110: 4576–4583.

    Article  CAS  Google Scholar 

  9. Kanakry CG, Tsai HL, Bolaños-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: 3817–3827.

    Article  CAS  Google Scholar 

  10. 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: 1380–1386.

    Article  CAS  Google Scholar 

  11. Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhäuser 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: 579–590.

    Article  CAS  Google Scholar 

  12. Gorin NC, Labopin M, Frassoni F, Milpied N, Attal M, Blaise D 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. J Clin Oncol 2008; 26: 3183–3188.

    Article  Google Scholar 

  13. Gorin NC, Labopin M, Meloni G, Pigneux A, Esteve J, Mohamad M . Impact of FLT3 ITD/NPM1 mutation status in adult patients with acute myelocytic leukemia autografted in first remission. Haematologica 2013; 98: e12–e14.

    Article  Google Scholar 

  14. Schlenk RF, Taskesen E, van Norden Y, Krauter J, Ganser A, Bullinger L et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood 2013; 122: 1576–1582.

    Article  CAS  Google Scholar 

  15. Gorin NC, Labopin M, Blaise D, Reiffers J, Meloni G, Michallet M et al. Higher incidence of relapse with peripheral blood rather than marrow as a source of stem cells in adults with acute myelocytic leukemia autografted during the first remission. J Clin Oncol 2009; 27: 3987–3993.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hematology and Bone Marrow Transplantation, Polytechnic University of Marche-Ospedali Riuniti, Ancona, Italy

    F Saraceni & A Olivieri

  2. National Registry GITMO & Data Managing, Ospedale San Martino, Genova, Italy

    B Bruno

  3. Department of Internal Medicine (DiMI), Hematology Clinic, University of Genoa, IRCCS AOU S. Martino-IST, Genova, Italy

    R M Lemoli & F Bonifazi

  4. Department of Cellular Biotechnologies and Hematology, Hematology, ‘Sapienza’ University of Rome, Rome, Italy

    G Meloni

  5. Department of Hematology, Rome Transplant Network, Stem Cell Transplant Unit, Tor Vergata University, Rome, Italy

    W Arcese

  6. Hematology 2 Unit, San Giovanni Battista Hospital and University, Turin, Italy

    M Falda

  7. Department of Oncology, Hematology and BMT Unit, San Raffaele Scientific Institute, Milano, Italy

    F Ciceri

  8. Department of Hematology, University of Pavia, Policlinico S Matteo-IRCCS, Pavia, Italy

    E P Alessandrino

  9. Hematology Department, University of Bari, Bari, Italy

    G Specchia

  10. Department of Hematology and Bone Marrow Transplant Unit Ospedale Cervello, Palermo, Italy

    R Scimè

  11. Department of Hematology, S Bortolo Hospital, Vicenza, Italy

    R Raimondi

  12. Institute of Haematology, Università Cattolica Sacro Cuore, Roma, Italy

    A Bacigalupo

  13. Haematology Department, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy

    A Bosi

  14. Hematology - BMT Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    F Onida

  15. Hematology and BMT Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

    A Rambaldi

Authors
  1. F Saraceni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Bruno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R M Lemoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Meloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W Arcese
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Falda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F Ciceri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E P Alessandrino
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G Specchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. R Scimè
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R Raimondi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Bacigalupo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A Bosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. F Onida
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. A Rambaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. F Bonifazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. A Olivieri
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the GITMO (Gruppo Italiano Trapianto di Midollo Osseo)

Corresponding authors

Correspondence to F Saraceni or A Olivieri.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saraceni, F., Bruno, B., Lemoli, R. 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 52, 163–166 (2017). https://doi.org/10.1038/bmt.2016.233

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.233

This article is cited by

Search

Advanced search

Quick links