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 Article
  • Published:

Cord Blood Stem Cells

Unrelated cord blood transplantation in CML: Japan Cord Blood Bank Network analysis

Bone Marrow Transplantation volume 42, pages 241–251 (2008)Cite this article

Abstract

We analysed 86 patients with CML who received unrelated cord blood transplantation (UCBT), identified through a registry of the Japan Cord Blood Bank Network. At transplantation, the median patient age was 39 years (range, 1–67 years); 38 patients were in chronic phase (CP), 13 in the accelerated phase (AP) and 35 in blast crisis (BC). Median duration from diagnosis to UCBT was 1.5 years (range, 0.2–14.6 years). A nucleated cell (NC) dose of more than 3.0 × 107 per kg was sufficient to achieve neutrophil (91%) and platelet recovery (86%), whereas the lower dose of NC achieved only 60 and 61%, respectively. The duration and type of pre-transplant treatment did not affect neutrophil or platelet recovery. Results of multivariate analysis indicated that older patients (>50 years) had a higher incidence of transplant-related mortality. Advanced-disease stage and lower doses of NCs were significantly associated with lower leukaemia-free and event-free survival. At 2-year survival for patients in CP, AP and BC was 71, 59 and 32%, respectively (P=0.0004). A pre-transplant European Group for Blood and Marrow Transplantation scoring system was effective in predicting the outcome of UCBT. We conclude that UCBT is a reasonable alternative therapy for patients with CML.

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
Figure 5

Similar content being viewed by others

References

  1. Gluckman E, Broxmeyer HA, Auerbach AD, Friedman HS, Douglas GW, Devergie A et al. Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 1989; 321: 1174–1178.

    Article  CAS  Google Scholar 

  2. Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D et al. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci USA 1989; 86: 3828–3832.

    Article  CAS  Google Scholar 

  3. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.

    Article  CAS  PubMed  Google Scholar 

  4. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 2004; 32: 397–407.

    Article  CAS  Google Scholar 

  5. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.

    Article  CAS  PubMed  Google Scholar 

  6. Talpaz M, Kantarjian H, Kurzrock R, Trujillo JM, Gutterman JU . Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann Intern Med 1991; 114: 532–538.

    Article  CAS  PubMed  Google Scholar 

  7. Lee MS, Kantarjian H, Talpaz M, Freireich EJ, Deisseroth A, Trujillo JM et al. Detection of minimal residual disease by polymerase chain reaction in Philadelphia chromosome-positive chronic myelogenous leukemia following interferon therapy. Blood 1992; 79: 1920–1923.

    CAS  PubMed  Google Scholar 

  8. Kantarjian HM, Cortes JE, O’Brien S, Giles F, Garcia-Manero G, Faderl S et al. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood 2003; 101: 97–100.

    Article  CAS  PubMed  Google Scholar 

  9. Deininger M, Buchdunger E, Druker BJ . The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005; 105: 2640–2653.

    Article  CAS  PubMed  Google Scholar 

  10. Cortes J, Talpaz M, O’Brien S, Jones D, Luthra R, Shan J et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res 2005; 11: 3425–3432.

    Article  CAS  PubMed  Google Scholar 

  11. Kantarjian H, Talpaz M, O’Brien S, Giles F, Faderl S, Verstovsek S et al. Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukemia—comparison with historic experience. Cancer 2005; 103: 2099–2108.

    Article  CAS  PubMed  Google Scholar 

  12. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355: 2408–2417.

    Article  CAS  Google Scholar 

  13. Cortes J, O’Brien S, Kantarjian H . Discontinuation of imatinib therapy after achieving a molecular response. Blood 2004; 104: 2204–2205.

    Article  CAS  PubMed  Google Scholar 

  14. Merante S, Orlandi E, Bernasconi P, Calatroni S, Boni M, Lazzarino M . Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation. Haematologica 2005; 90: 979–981.

    PubMed  Google Scholar 

  15. Bartholomeusz GA, Talpaz M, Kapuria V, Kong LY, Wang S, Estrov Z et al. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood 2007; 109: 3470–3478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ray A, Cowan-Jacob SW, Manley PW, Mestan J, Griffin JD . Identification of Bcr/Abl point mutations conferring resistance to the Abl kinase inhibitor AMN107 (Nilotinib) by a random mutagenesis study. Blood 2007; 109: 5011–5015.

    Article  CAS  PubMed  Google Scholar 

  17. Hochhaus A, Erben P, Ernst T, Mueller MC . Resistance to targeted therapy in chronic myelogenous leukemia. Semin Hematol 2007; 44 (1 Suppl 1): 15–24.

    Article  Google Scholar 

  18. Kimura S, Ashihara E, Maekawa T . New tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Curr Pharm Biotechnol 2006; 7: 371–379.

    Article  CAS  PubMed  Google Scholar 

  19. Weisberg E, Catley L, Wright RD, Moreno D, Banerji L, Ray A et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood 2007; 109: 2112–2120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Weisser M, Schleuning M, Haferlach C, Schwerdtfeger R, Kolb HJ . Allogeneic stem-cell transplantation provides excellent results in advanced stage chronic myeloid leukemia with major cytogenetic response to pre-transplant imatinib therapy. Leuk Lymphoma 2007; 48: 295–301.

    Article  CAS  PubMed  Google Scholar 

  21. Koh LP, Hwang WY, Chuah CT, Linn YC, Goh YT, Tan CH et al. Imatinib mesylate (STI-571) given concurrently with nonmyeloablative stem cell transplantation did not compromise engraftment and resulted in cytogenetic remission in a patient with chronic myeloid leukemia in blast crisis. Bone Marrow Transplant 2003; 31: 305–308.

    Article  CAS  PubMed  Google Scholar 

  22. Simula MP, Marktel S, Fozza C, Kaeda J, Szydlo RM, Nadal E et al. Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy. Leukemia 2007; 21: 943–948.

    Article  CAS  PubMed  Google Scholar 

  23. de Weger RA, Tilanus MG, Scheidel KC, van den Tweel JG, Verdonck LF . Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats. Br J Haematol 2000; 110: 647–653.

    Article  CAS  PubMed  Google Scholar 

  24. Sanz GF, Saavedra S, Jimenez C, Senent L, Cervera J, Planelles D et al. Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution. Bone Marrow Transplant 2001; 27: 693–701.

    Article  CAS  PubMed  Google Scholar 

  25. Rubinstein P, Dobrila L, Rosenfield RE, Adamson JW, Migliaccio G, Migliaccio AR et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci USA 1995; 92: 10119–10122.

    Article  CAS  Google Scholar 

  26. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  27. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood 2003; 102: 4290–4297.

    Article  CAS  Google Scholar 

  28. 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: 1087–1092.

    Article  CAS  PubMed  Google Scholar 

  29. Gratwohl A, Brand R, Apperley J, Crawley C, Ruutu T, Corradini P et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the chronic leukemia working party of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 2006; 91: 513–521.

    PubMed  Google Scholar 

  30. Nagamura-Inoue T, Shioya M, Sugo M, Cui Y, Takahashi A, Tomita S et al. Wash-out of DMSO does not improve the speed of engraftment of cord blood transplantation: follow-up of 46 adult patients with units shipped from a single cord blood bank. Transfusion 2003; 43: 1285–1295.

    Article  PubMed  Google Scholar 

  31. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.

    CAS  PubMed  Google Scholar 

  32. Reiter E, Greinix HT, Keil F, Brugger S, Rabitsch W, Schulenburg A et al. Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia. Ann Hematol 1999; 78: 507–513.

    Article  CAS  PubMed  Google Scholar 

  33. Barker JN, Davies SM, DeFor TE, Burns LJ, McGlave PB, Miller JS et al. Determinants of survival after human leucocyte antigen-matched unrelated donor bone marrow transplantation in adults. Br J Haematol 2002; 118: 101–107.

    Article  CAS  PubMed  Google Scholar 

  34. Morishima Y, Yabe T, Matsuo K, Kashiwase K, Inoko H, Saji H et al. Effects of HLA allele and killer immunoglobulin-like receptor ligand matching on clinical outcome in leukemia patients undergoing transplantation with T-cell-replete marrow from an unrelated donor. Biol Blood Marrow Transplant 2007; 13: 315–328.

    Article  CAS  PubMed  Google Scholar 

  35. Dini G, Lamparelli T, Rondelli R, Lanino E, Barbanti M, Costa C et al. Unrelated donor marrow transplantation for chronic myelogenous leukaemia. Br J Haematol 1998; 102: 544–552.

    Article  CAS  PubMed  Google Scholar 

  36. Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 2000; 6: 1018–1023.

    Article  CAS  PubMed  Google Scholar 

  37. Deininger M, Schleuning M, Greinix H, Sayer HG, Fischer T, Martinez J et al. The effect of prior exposure to imatinib on transplant-related mortality. Haematologica 2006; 91: 452–459.

    CAS  PubMed  Google Scholar 

  38. Seggewiss R, Lore K, Greiner E, Magnusson MK, Price DA, Douek DC et al. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood 2005; 105: 2473–2479.

    Article  CAS  PubMed  Google Scholar 

  39. Appel S, Balabanov S, Brummendorf TH, Brossart P . Effects of imatinib on normal hematopoiesis and immune activation. Stem Cells 2005; 23: 1082–1088.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Masato Takeuchi of Kitasato University Graduate School for the statistical discussion. We thank all of the physicians and staff at the hospitals and the 11 cord blood banks in Japan who collaborated on this study. We also thank all the data managers and officers of the Japan Cord Blood Bank Network and the Transplantation Data Management Committee. This work was supported in part by a Health and Labor Science Research Grant from the Ministry of Health, Labor and Welfare of Japan.

Author information

Authors and Affiliations

  1. Department of Cell Processing and Transfusion, Research Hospital, The Institute of Medical Science, University of Tokyo, Tokyo, Japan

    T Nagamura-Inoue & A Tojo

  2. Tokyo Cord Blood Bank, Tokyo, Japan

    T Nagamura-Inoue & A Tojo

  3. Department of Transfusion Medicine, Hyogo Medical University, Nishinomiya, Japan

    S Kai

  4. Hyogo Cord Blood Bank, Nishinomiya, Japan

    S Kai

  5. Hokkaido Red Cross Blood Center, Sapporo, Japan

    H Azuma

  6. Hokkaido Cord Blood Bank, Sapporo, Japan

    H Azuma

  7. Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo, Japan

    M Takanashi

  8. The Metro Tokyo Red Cross Cord Blood Bank, Tokyo, Japan

    M Takanashi

  9. Department of Paediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan

    K Isoyama

  10. Kanagawa Cord Blood Bank, Yokohama, Japan

    K Isoyama

  11. Department of Paediatric Haematology/Oncology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    K Kato

  12. Tokai Cord Blood Bank, Nagoya, Japan

    K Kato

  13. Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, University of Tokyo, Tokyo, Japan

    S Takahashi & A Tojo

  14. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    S Taniguchi

  15. Department of Haematology/Oncology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    K Miyamura

  16. Department of Hematology, Kitakyusyu City Medical Center Hospital, Kitakyusyu, Japan

    K Aoki

  17. Department of Hematology and Collagen Disease, National Hospital and Organization Kumamoto Medical Center, Kumamoto, Japan

    M Hidaka

  18. Division of Clinical Trial Safety Management, Research Hospital, The Institute of Medical Science, University of Tokyo, Tokyo, Japan

    F Nagamura

  19. Division of Biostatistics, Kitasato University Graduate School, Tokyo, Japan

    X M Fang

  20. Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan

    S Kato

  21. Tokai University Cord Blood Bank, Isehara, Japan

    S Kato

Authors
  1. T Nagamura-Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Kai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Azuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Takanashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Isoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K Miyamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K Aoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Hidaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. F Nagamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A Tojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. X M Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. S Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for Japan Cord Blood Bank Network

Corresponding author

Correspondence to T Nagamura-Inoue.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagamura-Inoue, T., Kai, S., Azuma, H. et al. Unrelated cord blood transplantation in CML: Japan Cord Blood Bank Network analysis. Bone Marrow Transplant 42, 241–251 (2008). https://doi.org/10.1038/bmt.2008.164

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.164

Keywords

This article is cited by

Search

Advanced search

Quick links