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:

Autologous Bone Marrow Transplantation in CML

Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-α

Leukemia volume 14, pages 2064–2069 (2000)Cite this article

Abstract

In chronic myelogenous leukemia (CML), autologous stem cell transplantation could be a promising new approach for patients with no cytogenetic response after interferon α (IFN-α) therapy. We report data on 28 CML patients autotransplanted in chronic phase with peripheral blood progenitor cells mobilized with G-CSF (5 μg/kg/day x 5 days) given subcutaneously while continuing IFN-α therapy. At mobilization, 23 patients (82%) were in complete hematological remission (CHR), 16 (57%) achieved a minor cytogenetic response (mcr). We obtained, after stimulation, a median of 37.4 × 109/l (6.9–108) white blood cells, 7.2 × 108/kg (2.2–16.6) mononuclear cells, 39 × 104/kg (4.8–403.5) CFU-GM and 4.2 × 106/kg (0–58.6) CD34+ cells. Six patients received GM-CSF after transplantation. All patients engrafted, with no significant influence stemming from the Sokal index score and pretransplantation IFN-α therapy duration. The first cytogenetic evaluation after transplantation showed 11 (39%) major cytogenetic response (Mcr), and nine (32%) mcr with no significant correlation between these responses, the Sokal index score, and pretransplantation IFN-α therapy duration, although there was a significant impact from GM-CSF administration (P = 0.01). After transplantation, 26 patients received IFN-α alone or associated with hydroxyurea. The median follow-up was 12 months after transplantation and 57 months after diagnosis. At the time of follow-up, nine patients were in CHR, six remained stable in chronic phase, three presented an mcr and one remained in Mcr. At the last follow-up, 22 patients were alive. We conclude that the results of this strategy are encouraging in poor IFN-α responders but that other prospective studies that try to maintain the cytogenetic responses obtained immediately after transplantation are needed.

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. Thomas ED, Clift RA, Fefer A, Appelbaum FR, Beatty P, Bensinger WI, Buckner CD, Cheever MA, Deeg HJ, Doney K, Flournoy N, Greenberg P, Hansen JA, Martin P, McGuffin R, Ramberg R, Sanders JE, Singer J, Stevart P, Storb R, Sullivan K, Weiden PL, Witherspoon R . Marrow transplantation for the treatment of chronic myelogenous leukemia Ann Intern Med 1986 104: 155–162

    CAS  PubMed  Google Scholar 

  2. Goldman JM . Management of chronic myeloid leukemia Blood 1994 8: 21–29

    CAS  Google Scholar 

  3. Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H, Yoshida T, Kimura A, Akaza T, Kamikawaji N, Kodera Y, Takaku F . Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program New Engl J Med 1998 339: 1177–1185

    CAS  PubMed  Google Scholar 

  4. Drobyski WR, Pelz C, Kabler-Babbitt C, Hessner M, Baxter-Lowe LA, Keever-Taylor CA . Successful unrelated marrow transplantation for patients over the age of 40 with chronic myelogenous leukemia Biol Blood Marrow Transplant 1998 4: 3–12

    CAS  PubMed  Google Scholar 

  5. Talpaz M . Prolonged survival in chronic myelogenous leukaemia following cytogenetic response to alpha interferon therapy Ann Intern Med 1995 122: 254–261

    PubMed  Google Scholar 

  6. Italian Cooperative Study Group on Chronic Myeloid Leukemia . Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia New Engl J Med 1994 330: 820–825

    Google Scholar 

  7. Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F, Bouabdallah R, Guyotat D, Cheron N, Nicolini F, Abgrall JF, Tanzer J . Interferon alfa-2b combined with cytarabine vs interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group New Engl J Med 1997 337: 223–229

    CAS  PubMed  Google Scholar 

  8. Goldman JM . Options for the management of chronic myeloid leukemia Leuk Lymphoma 1990 3: 159–163

    CAS  PubMed  Google Scholar 

  9. Reiffers J, Goldman JM, Meloni G, Cahn JY, Gratwohl A on behalf of the Chronic Leukemia Working Party of the EBMT . Autologous stem cell transplantation in chronic myelogenous leukemia: a retrospective analysis of the European Group for Bone Marrow Transplantation Bone Marrow Transplant 1994 14: 407–410

    CAS  PubMed  Google Scholar 

  10. McGlave PB, De Fabritiis P, Deisseroth A . Autologous transplant therapy for chronic myelogenous leukemia prolongs survival: results from eight transplant groups Lancet 1994 343: 1486–1491

    CAS  PubMed  Google Scholar 

  11. Reiffers J, Mahon FX, Boiron JM, Fabères C, Cony-Makhoul P, Broustet A . Autografting in chronic myeloid leukemia: an overview Leukemia 1996 10: 385–388

    CAS  PubMed  Google Scholar 

  12. Brenner MK, Rill DR, Moen RC, Krance RA, Mirro J Jr, Anderson WF, Ihle JN . Gene-marking to trace origin of relapse after autologous bone marrow transplantation Lancet 1993 341: 85–86

    CAS  PubMed  Google Scholar 

  13. Deisseroth AB, Zu Z, Claxton D, Hananian EG, Fu S, Ellerson D, Goldberg L, Thomas M, Janicek K, Anderson WF, Hester J, Korbling M, Durett A, Men R, Berenson R, Heimfeld S, Hamer J, Calvert L, Tibbits P, Talpaz M, Kantarjian H, Champlin R, Reading C . Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukaemia (CML) contribute to relapse after autologous bone marrow in CML Blood 1994 83: 3068–3076

    CAS  PubMed  Google Scholar 

  14. Coulombel L, Kalousek DK, Eaves CJ, Gupta CM, Eaves AC . Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia New Engl J Med 1983 308: 1493–1498

    CAS  PubMed  Google Scholar 

  15. McGlave PB, Arthur D, Miller WJ, Lasky L, Kersey J . Autologous transplantation for CML using marrow treated ex vivo with recombinant human interferon gamma Bone Marrow Transplant 1990 6: 115–120

    CAS  PubMed  Google Scholar 

  16. Carlo-Stella C, Mangoni L, Piovani G, Almmici C, Garau D, Caramatti C, Rizzoli V . In vitro purging in chronic myelogenous leukemia: effect of mafosfamide and recombinant granulocyte-macrophage colony-stimulating factor Bone Marrow Transplant 1991 8: 265–272

    CAS  PubMed  Google Scholar 

  17. Barnett MJ, Eaves CJ, Phillips GL, Gascoyne RD, Hogge DE, Horsman DE, Humphries RK, Klingemann HG, Lansdorp PM, Nantel SH, Reece DE, Shepherd JD, Spinelli JJ, Sutherland HJ, Eaves AC . Autografting with cultured marrow in chronic myeloid leukemia: results of a pilot study Blood 1994 84: 724–732

    CAS  PubMed  Google Scholar 

  18. De Fabritiis P, Amadori S, Petti MC, Mancini M, Montefusco E, Picardi A, Geiser T, Camphbell K, Calabretta B, Mandelli F . In vitro purging with BCR-ABL antisense oligonucleotides does not prevent haematology reconstitution after autologous bone marrow transplantation Leukemia 1995 9: 662–664

    Google Scholar 

  19. Ratajezak MZ, Hijia N, Catani L . Acute and chronic phase chronic myelogenous leukemia colony forming units are highly sensitive to the growth inhibitory effects of c-myb antisense oligodeoxynucleotides Blood 1992 79: 1956–1961

    Google Scholar 

  20. Estrov Z, Markowitz AB, KuzrockR, Wetzler M, Kantarjian HM, Ferrajoli A, Guttermann JU, Talpaz M . Suppression of chronic myelogenous leukemia colony growth by IL-4 Leukemia 1993 7: 214–220

    CAS  PubMed  Google Scholar 

  21. Bhatia R, Verfaille CM . Autografting for chronic myelogenous leukemia Curr Opin Hematol 1995 2: 436–443

    CAS  PubMed  Google Scholar 

  22. Carella AM, Podesta M, Frassoni F, Raffo MR, Pollicardo N, Pungolino E, Vimercati R, Sessarego M, Parodi C, Rabitti C, Ferrero R, Benvenuto F, Figari O, Carlier P, Levcasic G, Valbonesi M, Vitale V, Giordano D, Pierluigi D, Nati S, Guerracio A, Rosso C, Saglio G . Collection of normal blood repopulating cells during early hematopoietic recovery after intensive conventional chemotherapy in chronic myelogenous leukemia Bone Marrow Transplant 1993 12: 267–271

    CAS  PubMed  Google Scholar 

  23. Carella AM, Simonsson B, Link H, Lennard A, Boogaerts M, Gorin NC, Thomas-Martinez JF, Dabouz-Harrouche F, Gautier L, Badri N . Mobilization of Philadelphia (Ph1)-negative peripheral blood progenitor cells with chemotherapy and rHuG-CSF in chronic myelogenous leukaemia patients with a poor response to interferon-alpha Br J Haematol 1998 101: 111–118

    CAS  PubMed  Google Scholar 

  24. Reiffers J, Taylor K, Gluckman E, Gorin NC, Mahon FX, Miclea JM, Destrée D, Gautier L . Collection of Ph-negative progenitor cells with granulocyte-colony stimulating factor in patients with chronic myeloid leukaemia who respond to recombinant alpha-interferon Br J Haematol 1998 102: 639–646

    CAS  PubMed  Google Scholar 

  25. Archimbaud E, Michallet M, Philip I, Charrin C, Clapisson G, Belhabri A, Guilhot F, Stryckmans P, Adeleine P, Fiere D . Granulocyte colony-stimulating factor given in addition to interferon-alpha to mobilize peripheral blood stem cells for autologous transplantation in chronic myeloid leukaemia Br J Haematol 1997 99: 678–684

    CAS  PubMed  Google Scholar 

  26. Kantarjian HM, Keating MJ, Smith TL, Talpaz M, McCredie KB . Proposal for a simple synthesis prognostic staging system in chronic myelogenous leukemia Am J Med 1990 88: 1–8

    CAS  PubMed  Google Scholar 

  27. Cortes J, Kantarjian H, O'Brien S, Kurzrock R, Keating M, Talpaz M . GM-CSF can improve the cytogenetic response obtained with interferon-alpha therapy in patients with chronic myelogenous leukemia Leukemia 1998 12: 860–864

    CAS  PubMed  Google Scholar 

  28. Neuman HA, Fauser AA . Effect of interferon on pluripotent hemopoietic progenitors (CFU-GEMM) derived from human bone marrow Exp Hematol 1982 10: 587–591

    Google Scholar 

  29. Korbling M, Huh YO, Durett A, Mirza N, Miller P, Engel H, Anderlini P, van Besien K, Andreeff M, Przepiorka D, Deisseroth AB, Champlin R . Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy-1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease Blood 1995 86: 2842–2848

    CAS  PubMed  Google Scholar 

  30. Sheridan WP, Begley GC, Juttner C, Szer J, To LB, Maher D, McGrath KM, Morstyn G, Fox RM . Effects of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy Lancet 1992 339: 640–644

    CAS  PubMed  Google Scholar 

  31. Bedi A, Griffin CA, Barber JP, Vala MS, Hawkins AL, Sharkis SJ, Zehnbauer BA, Jones RJ . Growth factor-mediated terminal differentiation of chronic myeloid leukemia Cancer Res 1994 54: 5535–5538

    CAS  PubMed  Google Scholar 

  32. Giralt S, Escudier S, Kantarjian H, Deisseroth AB, Freireich EJ, Anderson BS, O'Brian S, Andreeff M, Fisher H, Cork A, Hirsch-Ginsberg C, Trujillo J, Stass S, Champlin R . Preliminary results of treatment with filgrastim for relapse of leukaemia and myelodysplasia after allogeneic bone marrow transplantation New Engl J Med 1993 329: 757–761

    CAS  PubMed  Google Scholar 

  33. Carreras E, Sierra J, Rovira M, Urbano-Ispiza A, Martinez C, Nomdedeu B, Cervantes F, Marin P, Rozman C, Monsterrat E . Successful autografting in chronic myelogenous leukaemia using Philadelphia-negative blood progenitor cells mobilized with rHuG-CSF alone in a patient responding to alpha-interferon Br J Haematol 1997 96: 421–423

    CAS  PubMed  Google Scholar 

  34. Carella AM, Cunningham I, Lerma E, Dejana A, Benvenuto F, Podseta M, Celesti L, Chimirri F, Abate M, Vassalo F, Figari O, Parodi C, Sessarego M, Valbinesi M, Carlier P, Prencipe E, Gatti AM, Van den Berg D, Hoffman R, Frassoni F . Mobilization and transplantation of Philadelphia-negative peripheral-blood progenitor cells early in chronic myelogenous leukaemia J Clin Oncol 1997 15: 1575–1582

    CAS  PubMed  Google Scholar 

  35. Carella AM, Frassoni F . ICE, mini-ICE or high-dose hydroxyurea to mobilize Philadelphia (Ph1)-negative PBPC in chronic myelogenous leukaemia (letter) Br J Haematol 1996 95: 213–215

    CAS  PubMed  Google Scholar 

  36. Gewirtz AM . Treatment of chronic myelogenous leukemia (CML) with c-myb antisense oligodeoxynucleotides Bone Marrow Transplant 1994 14: (Suppl. 3) S57-S61

    Google Scholar 

  37. Verfaillie CM, Miller WJ, Boylan K, McGlave PB . Selection of benign primitive hematopoietic progenitors in chronic myelogenous leukemia on the basis of HLA-DR antigen expression Blood 1992 79: 1003–1010

    CAS  PubMed  Google Scholar 

  38. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB . Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells Nature Med 1996 2: 561–566

    CAS  PubMed  Google Scholar 

  39. Carlo-Stella C, Mangoni L, Almici C, Caramatti C, Cottafavi L, Dotti GP, Rizzoli V . Autologous transplant for chronic myelogenous leukaemia using marrow treated ex vivo with mafosfamide Bone Marrow Transplant 1994 14: 425–432

    CAS  PubMed  Google Scholar 

  40. Gladstone DE, Bedi A, Miller CB, Noga SJ, Griffin CA, Piantadosi S, Cagnoni PJ, Brodsky RA, Smith BD, Douglas TT, Shpall EJ, Jones RJ . Philadelphia chromosome-negative engraftment after autologous transplantation with granulocyte–macrophage colony-stimulating factor for chronic myeloid leukemia Biol Blood Marrow Transplant 1999 5: 394–399

    CAS  PubMed  Google Scholar 

  41. Carlo-Stella C, Regazzi E, Andrizzi C, Savoldo B, Garau D, Montefusco E, Vignetti M, Mandelli F, Rizzoli V, Meloni G . Use of granulocyte–macrophage colony-stimulating factor (GM-CSF) in combination with hydroxyurea as post-transplant therapy in chronic myelogenous leukemia patients autografted with unmanipulated hematopoietic cells Haematologica 1997 82: 291–296

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France

    M Michallet, A Thiébaut, C Vigouroux, X Thomas, K Bilger, A Belhabri & D Fière

  2. Unité de Cytaphérèses, Centre Léon Bérard, Lyon, France

    I Philip

  3. Laboratoire d'Hématologie et Cytogénétique, Hôpital Edouard Herriot, Lyon, France

    C Charrin

  4. Service d'Hématologie, Hôpital Nord, Saint-Etienne, France

    D Guyotat

  5. Service d'Hématologie, Centre Hospitalier, Annecy, France

    B Corront

  6. Service de Médecine, Maladies du sang, Centre Hospitalier, Chalon-sur-Saône, France

    B Salles

  7. Service d'Hématologie, Centre Hospitalo-Universitaire Lyon Sud, Lyon, France

    C Dumontet

  8. Service de Médecins, Maladies du sang, Centre Hospitalier, Valence, France

    PY Péaud

  9. Service d'Hématologie, Hôpital Robert Debré, Reims, France

    JP Vilque

  10. Service d'Hématologie, Centre Hospitalier, Corbeil-Essone, France

    A Devidas

Authors
  1. M Michallet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Thiébaut
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I Philip
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Charrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Vigouroux
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K Bilger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Belhabri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D Guyotat
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. B Corront
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. B Salles
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. C Dumontet
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. PY Péaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. JP Vilque
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. A Devidas
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. D Fière
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michallet, M., Thiébaut, A., Philip, I. et al. Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-α. Leukemia 14, 2064–2069 (2000). https://doi.org/10.1038/sj.leu.2401956

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2401956

Keywords

Search

Advanced search

Quick links