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STEM CELL TRANSPLANTATION

Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia

Leukemia volume 36, pages 1132–1138 (2022)Cite this article

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Abstract

Cord blood transplantation (CBT) is an alternative donor transplantation method and has the advantages of rapid availability and the possibility of inducing a more potent graft-versus-leukemia effect, leading to a lower relapse rate for patients with non-remission relapse and refractory acute myeloid leukemia (R/R AML). This study aimed to investigate the impact of CBT, compared to human leukocyte antigen-matched related donor transplantation (MRDT). This study included 2451 adult patients with non-remission R/R AML who received CBT (1738 patients) or MRDT (713 patients) between January 2009 and December 2018. Five-year progression-free survival (PFS) and the prognostic impact of CBT were evaluated using a propensity score (PS) matching analysis. After PS matching, the patient characteristics were well balanced between the groups. The five-year PFS was 25.2% (95% confidence interval [CI]: 21.2–29.5%) in the CBT group and 18.1% (95% CI: 14.5–22.0%) in the MRDT group (P = 0.009). The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.69–1.00, P = 0.045); this was due to a more pronounced decrease in the relapse rate (HR: 0.78, 95% CI: 0.69–0.89, P < 0.001) than an increase in the NRM (1.42, 1.15–1.76, P = 0.001). In this population, CBT was associated with a better 5-year PFS than MRDT after allogeneic HSCT.

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Fig. 1: Patient selection process.
Fig. 2: Transplant outcomes in a propensity score-matched cohort.

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References

  1. DeWolf SE, Tallman MS. How I treat relapsed or refractory AML. Blood. 2020. https://doi.org/10.1182/blood.2019001982.

  2. Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373:1136–52.

    Article  Google Scholar 

  3. Wattad M, Weber D, Döhner K, Krauter J, Gaidzik VI, Paschka P, et al. Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure. Leukemia. 2017;31:1306–13.

    Article  CAS  Google Scholar 

  4. Nagler A, Savani BN, Labopin M, Polge E, Passweg J, Finke J, et al. Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. Lancet Haematol. 2015;2:e384–392.

    Article  Google Scholar 

  5. Brissot E, Labopin M, Ehninger G, Stelljes M, Brecht A, Ganser A, et al. Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukemia: a report on 1578 patients from the Acute Leukemia Working Party of the EBMT. Haematologica. 2019;104:524–32.

    Article  CAS  Google Scholar 

  6. Brissot E, Labopin M, Stelljes M, Ehninger G, Schwerdtfeger R, Finke J, et al. Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT. J Hematol Oncol. 2017;10:130.

    Article  Google Scholar 

  7. Baron F, Labopin M, Ruggeri A, Ehninger G, Bonifazi F, Stelljes M, et al. Umbilical cord blood versus unrelated donor transplantation in adults with primary refractory or relapsed acute myeloid leukemia: a report from Eurocord, the Acute Leukemia Working Party and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the EBMT. Blood Cancer J. 2019;9:46.

    Article  Google Scholar 

  8. Konuma T, Kato S, Ooi J, Oiwa-Monna M, Ebihara Y, Mochizuki S, et al. Single-unit cord blood transplantation after granulocyte colony-stimulating factor–combined myeloablative conditioning for myeloid malignancies not in remission. Biol Blood Marrow Transpl. 2014;20:396–401.

    Article  CAS  Google Scholar 

  9. Ballen KK, Lazarus H. Cord blood transplant for acute myeloid leukaemia. Br J Haematol. 2016;173:25–36.

    Article  Google Scholar 

  10. Dholaria B, Savani BN, Hamilton BK, Oran B, Liu HD, Tallman MS, et al. Hematopoietic cell transplantation in the treatment of newly diagnosed adult acute myeloid leukemia: an evidence-based review from the American Society of Transplantation and Cellular Therapy. Transpl Cell Ther. 2021;27:6–20.

    Article  CAS  Google Scholar 

  11. 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 

  12. 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 

  13. Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011;118:282–8.

    Article  CAS  Google Scholar 

  14. Chen Y-B, Aldridge J, Kim HT, Ballen KK, Cutler C, Kao G, et al. Reduced-intensity conditioning stem cell transplantation: comparison of double umbilical cord blood and unrelated donor grafts. Biol Blood Marrow Transpl. 2012;18:805–12.

    Article  Google Scholar 

  15. Sharma P, Purev E, Haverkos B, Pollyea DA, Cherry E, Kamdar M, et al. Adult cord blood transplant results in comparable overall survival and improved GRFS vs matched related transplant. Blood Adv. 2020;4:2227–35.

    Article  Google Scholar 

  16. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  Google Scholar 

  17. 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. J Am Soc Blood Marrow Transpl. 2009;15:367–9.

    Article  Google Scholar 

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

    Article  Google Scholar 

  19. Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med. 2013;32:2837–49.

    Article  Google Scholar 

  20. Breems DA, Van Putten WLJ, Huijgens PC, Ossenkoppele GJ, Verhoef GEG, Verdonck LF, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Am Soc Clin Oncol. 2005;23:1969–78.

    Article  Google Scholar 

  21. Chevallier P, Labopin M, Turlure P, Prebet T, Pigneux A, Hunault M, et al. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study. Leukemia. 2011;25:939–44.

    Article  CAS  Google Scholar 

  22. Duval M, Klein JP, He W, Cahn J-Y, Cairo M, Camitta BM, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Am Soc Clin Oncol. 2010;28:3730–8.

    Article  Google Scholar 

  23. Battipaglia G, Ruggeri A, Labopin M, Volin L, Blaise D, Socié G, et al. Refined graft-versus-host disease/relapse-free survival in transplant from HLA-identical related or unrelated donors in acute myeloid leukemia. Bone Marrow Transpl. 2018;53:1295–303.

    Article  CAS  Google Scholar 

  24. Davies SM, Kollman C, Anasetti C, Antin JH, Gajewski J, Casper JT, et al. Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood. 2000;96:4096–102.

    Article  CAS  Google Scholar 

  25. Akpek G, Pasquini MC, Logan B, Agovi M-A, Lazarus HM, Marks DI, et al. Effects of spleen status on early outcomes after hematopoietic cell transplantation. Bone Marrow Transpl. 2013;48:825–31.

    Article  CAS  Google Scholar 

  26. 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 

  27. 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 

  28. Kanda J, Hayashi H, Ruggeri A, Kimura F, Volt F, Takahashi S, 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. 2020;34:128–37.

    Article  CAS  Google Scholar 

  29. Shouval R, Fein JA, Labopin M, Kröger N, Duarte RF, Bader P, et al. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 2019;6:e573–e584.

    Article  Google Scholar 

  30. Yanada M, Konuma T, Yamasaki S, Kuwatsuka Y, Masuko M, Tanaka M, et al. Time-varying effects of graft type on outcomes for patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2020;26:307–15.

    Article  Google Scholar 

  31. Liu H, Sun Z, Geng L, Wang X, Ding K, Tong J, et al. Similar survival, but better quality of life after myeloablative transplantation using unrelated cord blood vs matched sibling donors in adults with hematologic malignancies. Bone Marrow Transpl. 2014;49:1063–9.

    Article  CAS  Google Scholar 

  32. Tong J, Xuan L, Sun Y, Huang D, Liu H, Zheng C, et al. Umbilical cord blood transplantation without antithymocyte globulin results in similar survival but better quality of life compared with unrelated peripheral blood stem cell transplantation for the treatment of acute leukemia—a retrospective study in China. Biol Blood Marrow Transpl. 2017;23:1541–8.

    Article  Google Scholar 

  33. Mehta RS, Holtan SG, Wang T, Hemmer MT, Spellman SR, Arora M, et al. Composite GRFS and CRFS outcomes after adult alternative donor HCT. J Clin Oncol. 2020;38:2062–76.

    Article  Google Scholar 

  34. Inamoto Y, Kimura F, Kanda J, Sugita J, Ikegame K, Nakasone H, et al. Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. Haematologica. 2016;101:1592–602.

    Article  CAS  Google Scholar 

  35. Miyawaki S. JSH guideline for tumors of hematopoietic and lymphoid tissues: leukemia 1. Acute myeloid leukemia (AML). Int J Hematol. 2017;106:310–25.

    Article  Google Scholar 

  36. Labopin M, Ruggeri A, Gorin NC, Gluckman E, Blaise D, Mannone L, et al. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France. Haematologica 2014;99:535–40.

    Article  Google Scholar 

  37. Preussler JM, Denzen EM, Majhail NS. Costs and cost-effectiveness of hematopoietic cell transplantation. J Am Soc Blood Marrow Transpl 2012;18:1620–8.

    Article  Google Scholar 

  38. Kiernan J, Damien P, Monaghan M, Shorr R, McIntyre L, Fergusson D, et al. Clinical studies of ex vivo expansion to accelerate engraftment after umbilical cord blood transplantation: a systematic review. Transfus Med Rev. 2017;31:173–82.

    Article  Google Scholar 

  39. Wagner JE, Brunstein CG, Boitano AE, DeFor TE, McKenna D, Sumstad D, et al. Phase I/II trial of StemRegenin-1 expanded umbilical cord blood hematopoietic stem cells supports testing as a stand-alone graft. Cell Stem Cell. 2016;18:144–55.

    Article  CAS  Google Scholar 

  40. Horwitz ME, Wease S, Blackwell B, Valcarcel D, Frassoni F, Boelens JJ, et al. Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide. J Am Soc Clin Oncol. 2019;37:367–74.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank all the physicians and data managers of the centers, who contributed to the collection of data on transplantation for the Japanese Data Center for Hematopoietic Cell Transplantation and the Transplant Registry Unified Management Program 2. We would like to express our gratitude to the Japan Society of Clinical Research for their support.

Author information

Authors and Affiliations

  1. Department of Hematology, Kobe City Hospital Organization Kobe City Medical Center General Hospital, Kobe, Japan

    Yoshimitsu Shimomura

  2. Department of Environmental Medicine and Population Science, Graduate School of Medicine, Osaka University, Suita, Japan

    Yoshimitsu Shimomura & Tomotaka Sobue

  3. Division of Precision Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shigeki Hirabayashi

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

    Tadakazu Kondo & Junya Kanda

  5. Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan

    Shohei Mizuno

  6. Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Takahiro Fujino

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

    Keisuke Kataoka

  8. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  9. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

  10. Department of Hematology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

    Shigesaburo Miyakoshi

  11. Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan

    Masatsugu Tanaka

  12. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    Toshiro Kawakita

  13. Department of Hematology, National Hospital Organization Sendai Medical Center, Sendai, Japan

    Hisayuki Yokoyama

  14. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Noriko Doki

  15. Department of Hematology/Oncology, Tokai University School of Medicine, Kanagawa, Japan

    Kaito Harada & Makoto Onizuka

  16. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Kajigaya, Kawasaki, Japan

    Atsushi Wake

  17. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Shuichi Ota

  18. Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan

    Satoru Takada

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

    Satoshi Takahashi

  20. Preparation Department, Japanese Red Cross Kinki Block Blood Center, Ibaraki, Japan

    Takafumi Kimura

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

    Takahiro Fukuda

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

    Yoshiko Atsuta

  23. Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan

    Yoshiko Atsuta

  24. Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan

    Masamitsu Yanada

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  1. Yoshimitsu Shimomura
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Contributions

YS designed the study, analyzed the data, performed the statistical analysis, and wrote the first draft of the manuscript. TS, SH, TK, SM, JK, TF, KK and MY critically reviewed the manuscript and analyzed data. All the other authors contributed to data collection. All authors approved the final version.

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Correspondence to Yoshimitsu Shimomura.

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Shimomura, Y., Sobue, T., Hirabayashi, S. et al. Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia. Leukemia 36, 1132–1138 (2022). https://doi.org/10.1038/s41375-021-01474-0

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