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.

  • Original Manuscript
  • Published:

The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial

Leukemia volume 17, pages 60–67 (2003)Cite this article

Abstract

Variable numbers of CD34+ cells can be harvested from the blood of AML patients in CR after G-CSF supported mobilization following consolidation chemotherapy. We hypothesized that a decreased ability to mobilize stem cells reflects a chemotherapy-induced reduction in the number of normal and leukemic stem cells. We therefore analyzed whether the mobilizing capacity of these patients was of prognostic significance. 342 AML-patients in first CR received daily G-CSF from day 20 of the consolidation course and underwent 1–6 aphereses to obtain a minimum dose of 2 x 106 CD34+ cells/kg. Afterwards they were randomized for autologous bone marrow (BM) or blood SCT. As a surrogate marker for the mobilizing capacity, the highest yield of CD34+ cells of a single apheresis was adopted. Patients could be categorized into four groups: no harvest (n = 76), low yield (<1 x 106 CD34+/kg; n = 50), intermediate yield (1–6.9 x 106 CD34+ cells/kg; n = 128) and high yield (≥7 x 106 CD34+ cells/kg; n = 88). The median follow-up was 3.4 years; 163 relapses and 16 deaths in CR were reported. Autologous blood or BM SCT was performed in 36%, 64%, 81% and 88%, respectively, of the patients assigned to the no harvest, low, intermediate and high CD34+ yield group. The 3-year disease-free survival rate was 46.7%, 65.0%, 50.4% and 26.9% (P = 0.0002) and the relapse incidence was 47.5%, 30.1%, 43.1% and 71.9% (P < 0.0001). Multivariate Cox's proportional hazards model showed that the CD34+ yield was the most important independent prognostic variable (P = 0.005) after cytogenetics. Patients with the highest mobilizing capacity have a poor prognosis due to an increased relapse incidence.

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Reiffers, J, Gaspard, MH, Maraninchi, D, Michallet, M, Marit, G, Stoppa, AM, Corront, B, David, B, Gastaut, JA, Scotto, JJ, Broustet, A, Carcassonne, Y & Hollard, D. Comparison of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukemia in first remission: a prospective controlled trial. Br J Haematol, (1989). 72, 57–63.

    Article  CAS  PubMed  Google Scholar 

  2. Reiffers, J, Stoppa, AM, Attal, M, Michallet, M, Marit, G, Blaise, D, Huguet, F, Corront, B, Cony-Makhoul, P, Gastaut, JA, Laurent, G, Molina, L, Broustet, A, Maraninchi, D, Pris, J, Hollard, D & Faberes, C Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: the BGMT 87 study. Leukemia, (1996). 10, 1874–1882.

    CAS  PubMed  Google Scholar 

  3. Harousseau, JL, Cahn, JY, Pignon, B, Witz, F, Milpied, N, Delain, M, Lioure, B, Lamy, T, Desablens, B, Guilhot, F, Caillot, D, Abgrall, JF, Francois, S, Briere, J, Guyotat, D, Casassus, P, Audhuy, B, Tellier, Z, Hurteloup, P & Herve, P Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM). Blood, (1997). 90, 2978–2986.

    CAS  PubMed  Google Scholar 

  4. Zittoun, RA, Mandelli, F, Willemze, R, de Witte, T, Labar, B, Resegotti, L, Leoni, F, Damasio, E, Visani, G, Papa, G, Caronia, F, Hayat, M, Stryckmans, P, Rotoli, B, Leoni, P, Peetermans, ME, Dardenne, M, Vegna, ML, Petti, MC, Solbu, G & Suciu, S for the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo ltaliano Malattie Ematologiche Maligne dell ‘Adulto (GIMEMA) Leukemia Cooperative Groups. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med, (1995). 332, 217–223.

    Article  CAS  PubMed  Google Scholar 

  5. Burnett, AK, Goldstone, AH, Stevens, R, Hann, IM, Rees, JK, Gray, RG & Wheatley, K Randomised comparison of addition autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet, (1998). 351, 700–708.

    Article  CAS  PubMed  Google Scholar 

  6. Martin, C, Torres, A, Leon, A, Rubio, V, Alvarez, MA, Herrera, C, Jean-Paul, E, Correa, MA, Rojas, R, Campos, R, Serrano, J, Romero, R, Roman, J, Guzman, JL, Flores, R, Falcon, M, Martinez, F & Gomez, P Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission. Role of intensification therapy in outcome. Bone Marrow Transplant, (1998). 21, 375–382.

    Article  CAS  PubMed  Google Scholar 

  7. Kessinger, A, Armitage, JO, Landmark, JD, Smith, DM & Weisenburger, DD Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. Blood, (1988). 71, 723–727.

    CAS  PubMed  Google Scholar 

  8. Schwartzberg, L, Birch, R, Blanco, R, Wittlin, F, Muscato, J, Tauer, K, Hazelton, B & West, W Rapid and sustained hematopoietic reconstitution by peripheral blood stem cell infusion alone following high-dose therapy. Bone Marrow Transplant, (1993). 11, 369–374.

    CAS  PubMed  Google Scholar 

  9. To, LB, Roberts, MM, Haylock, DN, Dyson, PG, Branford, AL, Thorp, D, Ho, JQ, Dart, GW, Horvath, N, Davy, ML, Olweny, CLM, Adbi, E & Juttner, CA Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant, (1992). 9, 277–284.

    CAS  PubMed  Google Scholar 

  10. Henon, PhR, Liang, H, Beck-Wirth, G, Eisenmann, JC, Lepers, M, Wunder, E & Kandel, G Comparison of hematopoietic and immune recovery after autologous bone marrow or blood stem cells transplants. Bone Marrow Transplant, (1992). 9, 285–291.

    CAS  PubMed  Google Scholar 

  11. de Witte, T, Keating, S, Suciu, S, Zittoun, R, Mandelli, F, Amadori, F, Resegotti, L, Varet, B, Belhabri, A, Fazi, P, Rodts, P & Willemze, R A randomized comparison of the value of autologous BMT versus autologous PSCT for patients with AML in first CR in the AML 10 trial of the EORTC LCG and GIMEMA. Blood, (2001). 98, Abstr. 3565

  12. de Witte, T, Suciu, S, Zittoun, R, Resegotti, L, Liso, V, Willemze, R, Belhabri, A, Amadori, S, Giustolisi, R, Labar, B, Fioritoni, G, Rossi-Ferrini, G, Leone, G, Jehn, U, Keating, S, Fazi, P, Rodts, P, Solbu, G & Mandelli, F The type of anthacycline administered during remission induction and consolidation therapy of AML has an impact on feasibility of subsequent autologous or allogeneic transplantation and induced marrow toxicity: Preliminary results of the EORTC/GIMEMA AML-10 randomized trial. Blood, (2000). 96, Abstr. 2167

  13. Yates, J, Glidewell, O, Wiernik, P, Cooper, MR, Steinberg, D, Dosik, H, Levy, R, Hoagland, C, Henry, P, Gottlieb, A, Cornell, C, Berenberg, J, Hutchison, JL, Raich, P, Nissen, N, Ellison, RR, Frelick, R, James, GW, Falkson, G, Silver, RT, Haurani, F, Green, M, Henderson, E, Leone, L & Holland, JF Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood, (1982). 60, 454–462.

    CAS  PubMed  Google Scholar 

  14. Mitelman, F (ed). An International System for Human Cytogenetic Nomenclature. S. Karger: Basel, 1995.

    Google Scholar 

  15. Klein, JP & Moeschberger, ML. Survival Analysis: Techniques for Censored and Truncated Data. Statistics for Biology and Health, Springer Verlag: New York (1997).

    Book  Google Scholar 

  16. Grimwade, D, Walker, H, Oliver, F, Wheatley, K, Harrison, C, Harrison, G, Rees, J, Hann, I, Stevens, R, Burnett, A & Goldstone, A The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. Blood, (1998). 92, 2322–2333.

    CAS  PubMed  Google Scholar 

  17. Slovak, ML, Kopecky, J, Casseleth, PA, Harrington, DH, Theil, KS, Mohamed, A, Paietta, E, Willman, CL, Head, DR, Rowe, JM, Forman, SJ & Appelbaum, FR 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). 15, 4075–4083.

    Google Scholar 

  18. Gorin, NC Autologous stem cell transplantation in acute myelocytic leukemia. Blood, (1998). 92, 1073–1090.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from the Kay Kendall Foundation, the Leukemia Cooperative Group of the EORTC and the National Cancer Institute (grant numbers 5U10 CA11488-22 through 5U10 CA11488-32). Its contents are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute. We acknowledge Saint Jude Children's Research Hospital for providing a SAS macro for the computations of the cumulative incidences of relapse and of death in CR. The following additional members of the EORTC or GIMEMA participated to this study: Dr Sinnige (Den Bosch), Dr Vreugdenhil (Veldhoven), Dr Stryckmans (Brussels), Dr Selleslag (Brugge), Dr De Bock (Antwerpen), Dr Berneman (Antwerpen), Dr Vermeulen (Verviers), Dr Feremans (Brussels), Dr Andrien (Liège), Dr Thyss (Nice), Dr Bourhis (Villejuif), Dr Dreyfus (Paris), Dr Roozendaal (Amsterdam), Dr Muus (Nijmegen), Dr Ribeiro (Porto), Dr Labar (Zagreb), Dr Jaksic (Zagreb), Dr Cermak (Prague), Dr Beksac (Ankara), Dr Indrak (Olomouc), Dr Sousa (Coimbra), Dr Damasio (Genova), Dr Rizzoli (Parma), Dr Leoni (Ancona), Dr Leone (Rome), Dr Melillo (S Giovani Rotondo), Dr De Blasio (Latina), Dr Lucarelli (Pesaro), Dr Peta (Catanzaro), Dr Saglio (Orbassano-Torino), Dr Volpe (Avellino), Dr Mirto (Palermo), Dr Rotoli (Napoli), Dr Broccia (Cagliari), Dr Fioritoni (Pescara), Dr Mariani (Palermo), Dr Bodini (Cremona), Dr Monaco (Foggia), Dr Gallamini (Cuneo). The EORTC Data Managers (M Dardenne, P Rodts and G Eeckhout) are also acknowledged.

Author information

Author notes

  1. S Keating and S Suciu: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Hematology, St Radboud University Hospital, Nijmegen, The Netherlands

    S Keating & T de Witte

  2. EORTC Data Center, Brussels, Belgium

    S Suciu & G Solbu

  3. Department of Hematology, Hôtel-Dieu, Paris, France

    R Zittoun

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

    F Mandelli & G Meloni

  5. Department of Hematology, Hospital Edouard Herriot, Lyon, France

    A Belhabri

  6. Department of Hematology, Ospedale San Eugenio, Rome, Italy

    S Amadori

  7. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    W Fibbe & R Willemze

  8. Department of Hematology, Hospital S Giovanni Battista, Torino, Italy

    E Gallo

  9. Department of Hematology, CHU Sart-Tilman, Liège, Belgium

    G Fillet

  10. Department of Hematology, Hospital Necker, Paris, France

    B Varet

  11. Center for Human Genetics, University of Leuven, Leuven, Belgium

    A Hagemeijer

  12. GIMEMA Data Center, Rome, Italy

    P Fazi

Authors
  1. S Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Suciu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T de Witte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Zittoun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F Mandelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Belhabri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Amadori
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W Fibbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Gallo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G Fillet
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. B Varet
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. G Meloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A Hagemeijer
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. P Fazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. G Solbu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. R Willemze
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the EORTC and GIMEMA Leukemia Groups

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keating, S., Suciu, S., de Witte, T. et al. The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial. Leukemia 17, 60–67 (2003). https://doi.org/10.1038/sj.leu.2402782

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402782

Keywords

This article is cited by

Search

Advanced search

Quick links