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:

I.v. BU/fludarabine plus melphalan or TBI in unrelated cord blood transplantation for high-risk hematological diseases

Bone Marrow Transplantation volume 50, pages 607–609 (2015)Cite this article

Subjects

Although a myeloablative dose of i.v. BU/fludarabine ( i.v. BU/Flu) has been widely accepted as a reduced toxicity myeloablative regimen for Allo-SCT from a related or unrelated donor,1 little information is available on the feasibility of the i.v. BU/Flu regimen in cord blood transplantation (CBT). Studies from Duke University, in which i.v. BU/Flu was used as the conditioning regimen followed by double CBT, demonstrated that only 2 of 10 patients engrafted with donor hematopoietic cells.2 To evaluate the safety and efficacy of the i.v. BU/Flu-conditioning regimen in CBT, we retrospectively reviewed 62 consecutive adult CBT recipients with i.v. BU/Flu-based conditioning regimens at our institute from February 2007 to March 2010.

The patients’ characteristics are summarized in Table 1. Their median age was 59 years (range, 21–72), with a median hematopoietic cell transplant-specific comorbidity index score of 2 (0–5). All were considered not to be proper candidates for conventional myeloablative therapy. Fifty-seven (92%) patients were not in remission and 16 (36%) had a prior history of Allo-SCT. All were transplanted with a single cord blood unit, and all received fludarabine (Flu; 25–30 mg/m2 once daily for 5–6 days, 125–180 mg/m2 per total) and i.v. BU (0.8 mg/kg four times a day for 2–4 days, 6.4–12.8 mg/kg per total). Melphalan (Mel; 40–70 mg/m2 once daily for 2 days, 80–140 mg/m2 per total) or TBI (2–8 Gy per total) were used in combination with i.v. BU/Flu regimens in all the patients. Pre-transplant conditioning was determined by each attending physician according to the patient’s condition, disease status and history of prior therapy. Engraftment, regimen-related toxicities (RRT), chimerism, GVHD, nonrelapse mortality (NRM), OS and disease-free survival (DFS) were assessed as previously reported.3, 4 All patients gave written informed consent for transplant, and this study was approved by the institutional review board.

Table 1 Patients' characteristics, regimen-related toxicity and GVHD
Full size table

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

References

  1. Ciurea SO, Andersson BS . Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009; 15: 523–536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Horwitz ME, Morris A, Gasparetto C, Sullivan K, Long G, Chute J et al. Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients. Biol Blood Marrow Transplant 2008; 14: 591–594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Miyakoshi S, Yuji K, Kami M, Kusumi E, Kishi Y, Kobayashi K et al. Successful engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with advanced hematological diseases. Clin Cancer Res 2004; 10: 3586–3592.

    Article  PubMed  Google Scholar 

  4. Uchida N, Wake A, Takagi S, Yamamoto H, Kato D, Matsuhashi Y et al. Umbilical cord blood transplantation after reduced-intensity conditioning for elderly patients with hematologic diseases. Biol Blood Marrow Transplant 2008; 14: 583–590.

    Article  PubMed  Google Scholar 

  5. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE . Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.

    Article  CAS  PubMed  Google Scholar 

  6. Komatsu T, Narimatsu H, Yoshimi A, Kurita N, Kusakabe M, Hori A et al. Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. Ann Hematol 2007; 86: 49–54.

    Article  CAS  PubMed  Google Scholar 

  7. Peters WP, Henner WD, Grochow LB, Olsen G, Edwards S, Stanbuck H et al. Clinical and pharmacologic effects of high dose single agent busulfan with autologous bone marrow support in the treatment of solid tumors. Cancer Res 1987; 47: 6402–6406.

    CAS  PubMed  Google Scholar 

  8. Theilgaard-Monch K, Raaschou-Jensen K, Palm H, Schjodt K, Heilmann C, Vindelov L et al. Flow cytometric assessment of lymphocyte subsets, lymphoid progenitors, and hematopoietic stem cells in allogeneic stem cell grafts. Bone Marrow Transplant 2001; 28: 1073–1082.

    Article  CAS  PubMed  Google Scholar 

  9. Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol 2010; 28: 2859–2867.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Patel P, Sweiss K, Nimmagadda S, Gao W, Rondelli D . Comorbidity index does not predict outcome in allogeneic myeloablative transplants conditioned with fludarabine/i.v. busulfan (FluBu4). Bone Marrow Transplant 2011; 46: 1326–1330.

    Article  CAS  PubMed  Google Scholar 

  11. El Kourashy S, Williamson T, Chaudhry MA, Savoie ML, Turner AR, Larratt L et al. Influence of comorbidities on transplant outcomes in patients aged 50 years or more after myeloablative conditioning incorporating fludarabine, BU and ATG. Bone Marrow Transplant 2011; 46: 1077–1083.

    Article  CAS  PubMed  Google Scholar 

  12. Alatrash G, de Lima M, Hamerschlak N, Pelosini M, Wang X, Xiao L et al. Myeloablative reduced-toxicity i.v. busulfan-fludarabine and allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia or myelodysplastic syndrome in the sixth through eighth decades of life. Biol Blood Marrow Transplant 2011; 17: 1490–1496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Barrett AJ, Savani BN . Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years experience with new transplant concepts and new therapeutic agents. Leukemia 2006; 20: 1661–1672.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are especially grateful to data coordinators Kaori Kobayashi, Madoka Narita, Rumiko Tsuchihashi and Naomi Yamada for their invaluable help in making this study possible. We also wish to thank all the physicians, nurses, pharmacists and support personnel for their care of patients in this study.

Author information

Authors and Affiliations

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

    H Yamamoto, N Uchida, N Matsuno, A Kon, A Nishida, H Ota, T Ikebe, N Nakano, K Ishiwata, S Takagi, M Tsuji, Y Asano-Mori, G Yamamoto, K Izutsu, K Masuoka, A Wake & S Taniguchi

  2. Okinaka Memorial Institute for Medical Research, Tokyo, Japan

    N Uchida, K Izutsu & S Taniguchi

  3. Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan

    H Araoka & A Yoneyama

  4. Department of Transfusion Medicine, Toranomon Hospital, Tokyo, Japan

    S Makino

Authors
  1. H Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Matsuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Kon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Ota
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Ikebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K Ishiwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. H Araoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S Takagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M Tsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Y Asano-Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. G Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. K Izutsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. K Masuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. A Wake
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. A Yoneyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. S Makino
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. S Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Uchida.

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

Yamamoto, H., Uchida, N., Matsuno, N. et al. I.v. BU/fludarabine plus melphalan or TBI in unrelated cord blood transplantation for high-risk hematological diseases. Bone Marrow Transplant 50, 607–609 (2015). https://doi.org/10.1038/bmt.2014.316

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.316

This article is cited by

Search

Advanced search

Quick links