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.

  • Article
  • Published:

Unrelated cord blood transplantation with myeloablative conditioning for pediatric acute lymphoblastic leukemia in remission: prognostic factors

Bone Marrow Transplantation volume 56, pages 357–367 (2021)Cite this article

Subjects

Abstract

The number of individuals undergoing unrelated cord blood transplantation (UCBT) has increased in recent years; however, information on prognostic factors is limited. We retrospectively analyzed data from 475 children and adolescents receiving UCBT with myeloablative conditioning for acute lymphoblastic leukemia (ALL) in complete remission (CR), based on a nationwide registry. In the total patient cohort, 5-year leukemia-free survival (LFS) and overall survival (OS) rates after UCBT were 61.1% and 67.7%, respectively. UCBT at first CR and UCBT after 2007 were associated with good survival, while grade II–IV acute graft-versus-host disease (GVHD) was associated with low relapse rate but did not affect survival. Analysis according to human leukocyte antigen (HLA) disparity revealed that tacrolimus-based GVHD prophylaxis resulted in higher OS and lower relapse rate and nonrelapse mortality (NRM) than cyclosporine-based GVHD prophylaxis in patients transplanted with 6/6 and ≤4/6 HLA-matched umbilical cord blood. Furthermore, grade II–IV acute GVHD was associated with good LFS and low relapse rate, without high NRM, in patients receiving 5/6 HLA-matched UCBT. These data indicate that prognostic factors for ALL differ depending on HLA disparity in UCBT.

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

Fig. 1: Outcomes of children and adolescents with ALL in complete remission after unrelated cord blood transplantation with myeloablative conditioning regimen.
Fig. 2: Outcomes of children and adolescents with ALL in complete remission after unrelated cord blood transplantation with myeloablative conditioning regimen.

Similar content being viewed by others

References

  1. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int. 2018;60:4–12.

    Article  Google Scholar 

  2. Conter V, Valsecchi MG, Parasole R, Putti MC, Locatelli F, Barisone E, et al. Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study. Blood. 2014;123:1470–8.

    Article  CAS  Google Scholar 

  3. Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005;366:635–42.

    Article  Google Scholar 

  4. Ko RH, Ji L, Barnette P, Bostrom B, Hutchinson R, Raetz E, et al. Outcome of patients treated for relapsed or refractory acute lymphoblastic leukemia: a Therapeutic Advances in Childhood Leukemia Consortium study. J Clin Oncol. 2010;28:648–54.

    Article  Google Scholar 

  5. Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001;97:2962–71.

    Article  CAS  Google Scholar 

  6. Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med. 2016;375:944–53.

    Article  Google Scholar 

  7. Brunstein CGL, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR, et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood. 2007;110:3064–70.

    Article  CAS  Google Scholar 

  8. Rodrigues CA, Sanz G, Brunstein CG, Sanz J, Wagner JE, Renaud M, et al. Analysis of risk factors for outcomes after unrelated cord blood transplantation in adults with lymphoid malignancies: a study by the Eurocord-Netcord and Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2009;27:256–63.

    Article  Google Scholar 

  9. Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, et al. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014;371:1685–94.

    Article  CAS  Google Scholar 

  10. Gutman JA, Leisenring W, Appelbaum FR, Woolfrey AE, Delaney C. Low relapse without excessive transplant-related mortality following myeloablative cord blood transplantation for acute leukemia in complete remission: a matched cohort analysis. Biol Blood Marrow Transplant. 2009;15:1122–9.

    Article  CAS  Google Scholar 

  11. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet. 2007;369:1947–54.

    Article  Google Scholar 

  12. Barker JN, Fei M, Karanes C, Horwitz M, Devine S, Kindwall-Keller TL, et al. Results of a prospective multicentre myeloablative double-unit cord blood transplantation trial in adult patients with acute leukaemia and myelodysplasia. Br J Haematol. 2015;168:405–12.

    Article  Google Scholar 

  13. Michel G, Galambrun C, Sirvent A, Pochon C, Bruno B, Jubert C, et al. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome. Blood. 2016;127:3450–7.

    Article  CAS  Google Scholar 

  14. Kurtzberg J, Prasad VK, Carter SL, Wagner JE, Baxter-Lowe LA, Wall D, et al. Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. Blood. 2008;112:4318–27.

    Article  CAS  Google Scholar 

  15. Eapen M, Kurtzberg J, Zhang MJ, Hattersely G, Fei M, Mendizabal A, et al. Umbilical cord blood transplantation in children with acute leukemia: impact of conditioning on transplantation outcomes. Biol Blood Marrow Transplant. 2017;23:1714–21.

    Article  Google Scholar 

  16. Page KM, Labopin M, Ruggeri A, Michel G, Diaz de Heredia C, O’Brien T, et al. Factors associated with long-term risk of relapse after unrelated cord blood transplantation in children with acute lymphoblastic leukemia in remission. Biol Blood Marrow Transplant. 2017;23:1350–8.

    Article  Google Scholar 

  17. Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.

    Article  Google Scholar 

  18. Atsuta Y. Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). Int J Hematol. 2016;103:3–10.

    Article  Google Scholar 

  19. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

    Article  Google Scholar 

  20. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.

    Article  Google Scholar 

  21. 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  Google Scholar 

  22. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.

    Article  Google Scholar 

  23. Kanda Y. Investigation of the freely available easy-to-use software’EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  Google Scholar 

  24. Kato K, Yoshimi A, Ito E, Oki K, Hara J, Nagatoshi Y, et al. Cord blood transplantation from unrelated donors for children with acute lymphoblastic leukemia in Japan: the impact of methotrexate on clinical outcomes. Biol Blood Marrow Transplant. 2011;17:1814–21.

    Article  CAS  Google Scholar 

  25. Shigemura T, Sakashita K, Okura E, Morita D, Komori K, Kurata T, et al. Comparative analysis of graft-versus-host disease prophylaxis with tacrolimus in combination with methylprednisolone or methotrexate after umbilical cord blood transplantation. Int J Hematol. 2020. https://doi.org/10.1007/s12185-020-02826-9.

  26. Miyakoshi S, Kami M, Tanimoto T, Yamaguchi T, Narimatsu H, Kusumi E, et al. Tacrolimus as prophylaxis for acute graft-versus-host disease in reduced intensity cord blood transplantation for adult patients with advanced hematologic diseases. Transplantation. 2007;84:316–22.

    Article  CAS  Google Scholar 

  27. Uchida N, Wake A, Nakano N, Ishiwata K, Takagi S, Tsuji M, et al. Mycophenolate and tacrolimus for graft-versus-host disease prophylaxis for elderly after cord blood transplantation: a matched pair comparison with tacrolimus alone. Transplantation. 2011;92:366–71.

    Article  CAS  Google Scholar 

  28. Miyamoto T, Takashima S, Kato K, Takase K, Yoshimoto G, Yoshida S, et al. Comparison of cyclosporine and tacrolimus combined with mycophenolate mofetil in prophylaxis for graft-versus-host disease after reduced-intensity umbilical cord blood transplantation. Int J Hematol. 2017;105:92–9.

    Article  CAS  Google Scholar 

  29. Atsuta Y, Kanda J, Takanashi M, Morishima Y, Taniguchi S, Takahashi S, et al. Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia. Haematologica. 2013;98:814–22.

    Article  Google Scholar 

  30. Storb R, Gyurkocza B, Storer BE, Sorror ML, Blume K, Niederwieser D, et al. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2013;31:1530–8.

    Article  CAS  Google Scholar 

  31. Stern M, de Wreede LC, Brand R, van Biezen A, Dreger P, Mohty M, et al. Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis. Leukemia. 2014;28:2235–40.

    Article  CAS  Google Scholar 

  32. Kato M, Kurata M, Kanda J, Kato K, Tomizawa D, Kudo K, et al. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone Marrow Transplant. 2019;54:68–75.

    Article  Google Scholar 

  33. Bunin N, Aplenc R, Kamani N, Shaw K, Cnaan A, Simms S. Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium Study. Bone Marrow Transplant. 2003;32:543–8.

    Article  CAS  Google Scholar 

  34. Kebriaei P, Anasetti C, Zhang MJ, Wang HL, Aldoss I, de Lima M, et al. Intravenous busulfan compared with total body irradiation pretransplant conditioning for adults with acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2018;24:726–33.

    Article  CAS  Google Scholar 

  35. Mohty B, Mohty M. Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: an update. Blood Cancer J. 2011;1:e16.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all the staff at the hospitals and centers who contributed valuable data to the JSHCT registry. We also thank all the members of the data management committees of the JSHCT. This work was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from Japan Agency for Medical Research and Development, AMED, under Grant Number 19ek0510023h0002.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan

    Yuta Kawahara & Akira Morimoto

  2. Department of Pediatrics, Kitakyushu City Yahata Hospital, Kitakyushu, Japan

    Jiro Inagaki

  3. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Katsuyoshi Koh

  4. Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    Maiko Noguchi

  5. Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroaki Goto

  6. Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Nao Yoshida

  7. Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan

    Yuko Cho

  8. Department of Pediatrics, Sapporo Medical University Hospital, Sapporo, Japan

    Tsukasa Hori

  9. Department of Pediatrics, The University of Tokyo Hospital, Tokyo, Japan

    Mitsuteru Hiwatari

  10. Division of Pediatric Hematology and Oncology, Ibaraki Children’s Hospital, Mito, Japan

    Keisuke Kato

  11. Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan

    Atsushi Ogawa

  12. Department of Cancer Immunotherapy/Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan

    Yoshiko Hashii

  13. Department of Hematology/Oncology, Osaka Women’s and Children’s Hospital, Izumi, Japan

    Masami Inoue

  14. Central Japan Cord Blood Bank, Seto, Japan

    Koji Kato

  15. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

  16. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

  17. Division of Hematology, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan

    Fumihiko Kimura

  18. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Motohiro Kato

Authors
  1. Yuta Kawahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Morimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiro Inagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katsuyoshi Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maiko Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroaki Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nao Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuko Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tsukasa Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mitsuteru Hiwatari
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Keisuke Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Atsushi Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yoshiko Hashii
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Masami Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Koji Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yoshiko Atsuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Fumihiko Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Motohiro Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YK is the principal investigator and takes principal responsibility for the paper. YK, AM, JI, KoKa, FK, and MK designed the study. KKo, MN, HG, NY, YC, TH, MH, KeKa, AO, YH, MI, KoKa, and YA recruited the patients and collected the data. YK analyzed the data. YK and AM wrote the manuscript. All authors discussed the results, commented on the manuscript, and gave their final approval of the manuscript.

Corresponding author

Correspondence to Yuta Kawahara.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawahara, Y., Morimoto, A., Inagaki, J. et al. Unrelated cord blood transplantation with myeloablative conditioning for pediatric acute lymphoblastic leukemia in remission: prognostic factors. Bone Marrow Transplant 56, 357–367 (2021). https://doi.org/10.1038/s41409-020-01019-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-01019-6

Search

Advanced search

Quick links