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Epidemiology

Prognostic factors for adult single cord blood transplantation among European and Japanese populations: the Eurocord/ALWP-EBMT and JSHCT/JDCHCT collaborative study

Leukemia volume 34, pages 128–137 (2020)Cite this article

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Abstract

Large differences in patient and transplant backgrounds make it difficult to identify consistent prognostic factors of unrelated cord blood transplantation (UCBT) among different populations. Thus, we performed a collaborative study between Eurocord/ALWP-EBMT and JSHCT/JDCHCT. Adults with acute leukaemia who underwent a single UCBT were eligible. In total, 3764 and 1027 patients of the JSHCT/JDCHCT and Eurocord/ALWP-EBMT registries, respectively, were included. The median ages of the Japanese and European cohorts were 51 and 38 years, respectively. Three or more HLA mismatches were more frequently observed in the Japanese cohort. The median total nucleated cell (TNC) counts were 2.58 and 3.51 × 107/kg in the Japanese and European cohorts, respectively. Anti-thymocyte globulin was used in only 2% of the Japanese cohort compared with 65% of the European cohort. The 3-year overall survival (OS) was 41% in JSHCT/JDCHCT and 33% in Eurocord/ALWP-EBMT. In the multivariate analysis, TNC dose and HLA matching had no significant effect on OS in either cohort, whereas year of transplantation, age, and refined disease risk index affected OS in both cohorts. Despite considerable differences in characteristics between the Japanese and European cohorts, we observed similar prognostic factors affecting UCBT outcomes in adult patients with acute leukaemia in both registries.

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References

  1. Rocha V. Umbilical cord blood cells from unrelated donor as an alternative source of hematopoietic stem cells for transplantation in children and adults. Semin Hematol. 2016;53:237–45.

    Article  Google Scholar 

  2. Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, et al. One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol. 2015;2:e91–100.

    Article  Google Scholar 

  3. Cohen YC, Scaradavou A, Stevens CE, Rubinstein P, Gluckman E, Rocha V, et al. Factors affecting mortality following myeloablative cord blood transplantation in adults: a pooled analysis of three international registries. Bone Marrow Transpl. 2011;46:70–6.

    Article  CAS  Google Scholar 

  4. Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years and beyond. Blood. 2013;122:491–8.

    Article  CAS  Google Scholar 

  5. 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 

  6. Rocha V, Gluckman E. Eurocord-Netcord r, European B, Marrow Transplant g Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factors. Br J Haematol. 2009;147:262–74.

    Article  CAS  Google Scholar 

  7. Kai S, Wake A, Okada M, Kurata M, Atsuta Y, Ishikawa J, et al. Double-unit cord blood transplantation after myeloablative conditioning for patients with hematologic malignancies: a multicenter phase II study in Japan. Biol Blood Marrow Transpl. 2013;19:812–9.

    Article  Google Scholar 

  8. Barker JN, Kurtzberg J, Ballen K, Boo M, Brunstein C, Cutler C, et al. Optimal practices in unrelated donor cord blood transplantation for hematologic malignancies. Biol Blood Marrow Transpl. 2017;23:882–96.

    Article  Google Scholar 

  9. Hough R, Danby R, Russell N, Marks D, Veys P, Shaw B, et al. Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols. Br J Haematol. 2016;172:360–70.

    Article  Google Scholar 

  10. Eapen M, Klein JP, Sanz GF, Spellman S, Ruggeri A, Anasetti C, et al. Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol. 2011;12:1214–21.

    Article  CAS  Google Scholar 

  11. Eapen M, Klein JP, Ruggeri A, Spellman S, Lee SJ, Anasetti C, et al. Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy. Blood. 2014;123:133–40.

    Article  CAS  Google Scholar 

  12. Barker JN, Scaradavou A, Stevens CE. Combined effect of total nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematologic malignancies. Blood. 2010;115:1843–9.

    Article  CAS  Google Scholar 

  13. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  Google Scholar 

  14. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–9.

    CAS  PubMed  Google Scholar 

  15. 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 Transpl. 2009;15:367–9.

    Article  Google Scholar 

  16. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.

    Article  CAS  Google Scholar 

  17. Fine JP, Gray RJ. A proportional hazards model for subdistribution of a competing risk. J Am Stat Assoc. 1999;94:456–509.

    Article  Google Scholar 

  18. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71.

    Article  CAS  Google Scholar 

  19. Shouval R, Ruggeri A, Labopin M, Mohty M, Sanz G, Michel G, et al. An integrative scoring system for survival prediction following umbilical cord blood transplantation in acute leukemia. Clin Cancer Res. 2017;23:6478–86.

    Article  Google Scholar 

  20. Ballen KK, Logan BR, Laughlin MJ, He W, Ambruso DR, Armitage SE, et al. Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation. Biol Blood Marrow Transpl. 2015;21:688–95.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. 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 

  23. Sanz J, Wagner JE, Sanz MA, DeFor T, Montesinos P, Bachanova V, et al. Myeloablative cord blood transplantation in adults with acute leukemia: comparison of two different transplant platforms. Biol Blood Marrow Transpl. 2013;19:1725–30.

    Article  Google Scholar 

  24. Morishima Y, Morishita Y, Tanimoto M, Ohno R, Saito H, Horibe K, et al. Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group. Blood. 1989;74:2252–6.

    Article  CAS  Google Scholar 

  25. Oh H, Loberiza FR Jr., Zhang MJ, Ringden O, Akiyama H, Asai T, et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood. 2005;105:1408–16.

    Article  CAS  Google Scholar 

  26. Ikeda N, Kojima H, Nishikawa M, Hayashi K, Futagami T, Tsujino T, et al. Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study. Tissue Antigens. 2015;85:252–9.

    Article  CAS  Google Scholar 

  27. Kanda J, Brazauskas R, Hu ZH, Kuwatsuka Y, Nagafuji K, Kanamori H, et al. Graft-versus-host disease after HLA-matched sibling bone marrow or peripheral blood stem cell transplantation: comparison of North American Caucasian and Japanese populations. Biol Blood Marrow Transpl. 2016;22:744–51.

    Article  CAS  Google Scholar 

  28. de Koning C, Admiraal R, Nierkens S, Boelens JJ. Immune reconstitution and outcomes after conditioning with anti-thymocyte-globulin in unrelated cord blood transplantation; the good, the bad, and the ugly. Stem Cell Invest. 2017;4:38.

    Article  Google Scholar 

  29. Pascal L, Tucunduva L, Ruggeri A, Blaise D, Ceballos P, Chevallier P, et al. Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation. Blood. 2015;126:1027–32.

    Article  CAS  Google Scholar 

  30. Admiraal R, Lindemans CA, van Kesteren C, Bierings MB, Versluijs AB, Nierkens S, et al. Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation. Blood. 2016;128:2734–41.

    Article  CAS  Google Scholar 

  31. Brunstein CG, Weisdorf DJ, DeFor T, Barker JN, Tolar J, van Burik JA, et al. Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood. 2006;108:2874–80.

    Article  CAS  Google Scholar 

  32. Takahashi S, Iseki T, Ooi J, Tomonari A, Takasugi K, Shimohakamada Y, et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood. 2004;104:3813–20.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED (YA and JK) and JSPS KAKENHI Grant Number 18K08325 (JK).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Junya Kanda

  2. Eurocord, Hospital Saint Louis, AP-HP, IUH University Paris VII, Paris, France

    Hiromi Hayashi, Annalisa Ruggeri, Fernanda Volt, Karina Tozatto-Maio, Vanderson Rocha & Eliane Gluckman

  3. Monacord, Centre Scientifique de Monaco, Monaco, Monaco

    Hiromi Hayashi, Annalisa Ruggeri, Fernanda Volt, Karina Tozatto-Maio, Vanderson Rocha & Eliane Gluckman

  4. Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children’s Hospital, Roma, Italy

    Annalisa Ruggeri & Mohamad Mohty

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

    Fumihiko Kimura

  6. Division of Molecular Therapy, The Advanced Clinical Research Center The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Satoshi Takahashi

  7. Faculté de Médicine Saint-Antoine and European Group of Blood and Bone Marrow Transplantation (EBMT) Data Office, Paris, France

    Myriam Labopin, Mohamad Mohty & Arnon Nagler

  8. Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan

    Shinichi Kako

  9. Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

    Karina Tozatto-Maio

  10. Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Shingo Yano

  11. Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    Guillermo Sanz

  12. CIBERONC, Madrid, Spain

    Guillermo Sanz

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

    Naoyuki Uchida

  14. Ospedale San Martino Department of Haematology II, Genova, Italy

    Maria Teresa Van Lint

  15. Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Seiko Kato

  16. Service d’hematologie et therapie cellulaire, CHU Bordeaux, 33000, Bordeaux, France

    Edouard Forcade

  17. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    Heiwa Kanamori

  18. Hospital Santa Creu i Sant Pau Hematology Department, Barcelona, Catalunya, Spain

    Jorge Sierra

  19. Department of Internal Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

    Yuju Ohno

  20. Azienda Ospedaliera Universitaria Careggi Cell Therapy and Transfusion Medicine Unit, Firenze, Italy

    Riccardo Saccardi

  21. Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  22. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Tatsuo Ichinohe

  23. Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan

    Minoko Takanashi

  24. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Shinichiro Okamoto

  25. Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel

    Arnon Nagler

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

    Yoshiko Atsuta

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  1. Junya Kanda
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Contributions

JK, HH, YA, and EG designed the research. JK, YA, and EG organized the project. JK, HH, and YA performed the statistical analysis; JK, HH, AR, FK, FV, ST, ML, SKako, SY, VR, SO, AN, YA, and EG interpreted the data; JK, HH, AR, FV, NU, SKato, HK, and YO gathered the data; JK wrote the first draft and all other authors critically reviewed the draft and approved the final version for publication.

Corresponding author

Correspondence to Junya Kanda.

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Conflict of interest

JK reports honoraria from Chugai Pharmaceutical Co., Ltd., Celgene K.K., Otsuka Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Takeda Pharmaceutical Company Limited., Astellas Pharma Inc., Bristol-Myers Squibb, Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., JCR Pharmaceuticals Co., Ltd., Pfizer Japan Inc., Kyowa Kirin, and MSD Pharma, outside the submitted work. GS reports grants, honoraria, advisory role, and travel accommodations expenses from Celgene, advisory role from Abbvie, Helsinn Healthcare, Janssen, Roche, Amgen, Boehringer Ingelheim, and Novartis, and travel accommodations expenses from Takeda and Gilead Sciences, outside the submitted work. EF reports grants from Neovii, outside the submitted work. SKako reports honoraria from Chugai Pharmaceutical Co., Ltd., Celgene K.K., Otsuka Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Takeda Pharmaceutical Company Limited., Astellas Pharma Inc., Bristol-Myers Squibb, Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Pfizer Japan Inc., outside the submitted work. JS reports and Advisory and Speaker’s Bureau for Novartis, Pfizer, Celgene, Daiichi-Sankyo and Jazz Pharmaceuticals. SY reports grants from Kyowa Kirin, Astellas Pharma, Chugai Pharma, Mochida Pharma, Lilly Pharma, Takeda Pharma, MSD Pharma, Pfizer, Dai Nippon Sumitomo Pharma, and Ono Pharma, outside the submitted work.YA reports honoraria from CHUGAI PHARMACEUTICAL CO., LTD., Kyowa Kirin Co., Ltd, Bristol-Myers Squibb Co., Ltd, Yakult Honsha Co., Ltd., Janssen Pharmaceutical K.K., Otsuka Pharmaceutical Co., Ltd, and Mochida Pharmaceutical Co., Ltd, outside the submitted work. Other authors declare that they have no conflict of interest.

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Kanda, J., Hayashi, H., Ruggeri, A. et al. Prognostic factors for adult single cord blood transplantation among European and Japanese populations: the Eurocord/ALWP-EBMT and JSHCT/JDCHCT collaborative study. Leukemia 34, 128–137 (2020). https://doi.org/10.1038/s41375-019-0534-5

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