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


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.


  1. 1.

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

    Article  Google Scholar 

  2. 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.

    CAS  Article  Google Scholar 

  3. 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. 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. 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.

    CAS  Article  Google Scholar 

  6. 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. 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.

    CAS  Article  Google Scholar 

  8. 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. 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.

    CAS  Article  Google Scholar 

  10. 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.

    CAS  Article  Google Scholar 

  11. 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. 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. 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.

    CAS  Article  Google Scholar 

  14. 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.

    CAS  Article  Google Scholar 

  15. 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. 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. 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. 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. 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. 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. 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.

    CAS  Article  Google Scholar 

  22. 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. 23.

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

    CAS  Article  Google Scholar 

  24. 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.

    CAS  Article  Google Scholar 

  25. 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. 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.

    CAS  Article  Google Scholar 

  27. 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.

    CAS  Article  Google Scholar 

  28. 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.

    CAS  Article  Google Scholar 

  29. 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. 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.

    CAS  Article  Google Scholar 

  31. 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.

    CAS  Article  Google Scholar 

  32. 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. 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.

    CAS  Article  Google Scholar 

  34. 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.

    CAS  Article  Google Scholar 

  35. 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.

    CAS  Article  Google Scholar 

Download references


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




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

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 (2020). https://doi.org/10.1038/s41409-020-01019-6

Download citation