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.

Impact of donor types on reduced-intensity conditioning allogeneic stem cell transplant for mature lymphoid malignancies

Abstract

We retrospectively compared the outcomes of reduced-intensity conditioning (RIC) transplantation from matched related donors (MRD; n = 266), matched unrelated donors (MUD; n = 277), and umbilical cord blood (UCB; n = 513) for mature lymphoid malignancies. The 3-year overall survival rates for the MRD, MUD, and UCB groups were 54%, 59%, and 40%, respectively (P < 0.001). Multivariate analysis showed no differences in survival between the MRD group and the MUD or UCB group. However, survival was significantly affected by the conditioning regimen and graft-versus-host disease (GVHD) prophylaxis in the UCB group, but not in the MRD and MUD groups. Notably, multivariate analysis showed that the risk of overall mortality in the UCB recipients who received the optimal conditioning regimen and GVHD prophylaxis (n = 116) was lower than that in the MRD group (relative risk [RR], 0.69; P = 0.03) and tended to be lower than that in the MUD group (RR, 0.75; P = 0.09). Our results suggest that UCB transplantation performed with the optimal conditioning regimen and GVHD prophylaxis is highly effective. Moreover, UCB is readily available. Thus, UCB transplantation with the optimal conditioning regimen and GVHD prophylaxis is preferable to MUD transplantation when MRD are not available in the setting of RIC transplantation for mature lymphoid malignancies.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Overall survival of the MRD, MUD, and UCB groups.
Fig. 2: Overall survival, relapse/progression, and NRM of the MRD, MUD, optimal UCB, and suboptimal UCB groups.
Fig. 3: Hematopoietic recovery and GVHD of the MRD, MUD, optimal UCB, and suboptimal UCB groups.
Fig. 4: Forest plots showing the impact of the donor type on the OS of different subgroups of patients.

References

  1. 1.

    Shah GL, Moskowitz CH. Transplant strategies in relapsed/refractory Hodgkin lymphoma. Blood. 2018;131:1689–1697.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Fenske TS, Hamadani M, Cohen JB, Costa LJ, Kahl BS, Evens AM, et al. Allogeneic hematopoietic cell transplantation as curative therapy for patients with non-Hodgkin lymphoma: increasingly successful application to older patients. Biol Blood Marrow Transpl. 2016;22:1543–1551.

    Google Scholar 

  3. 3.

    Martínez C, Gayoso J, Canals C, Finel H, Peggs K, Dominietto A, et al. Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for Hodgkin lymphoma: a registry study of the lymphoma working party of the European Society for Blood and Marrow Transplantation. J Clin Oncol. 2017;35:3425–3432.

    PubMed  Google Scholar 

  4. 4.

    Dreger P, Sureda A, Ahn KW, Eapen M, Litovich C, Finel H, et al. PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL. Blood Adv. 2019;3:360–369.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Bachanova V, Burns LJ, Wang T, Carreras J, Gale RP, Wiernik PH, et al. Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor. Bone Marrow Transpl. 2015;50:197–203.

    CAS  Google Scholar 

  6. 6.

    Rodrigues CA, Rocha V, Dreger P, Brunstein C, Sengeloev H, Finke J, et al. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood. Haematologica. 2014;99:370–377.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Majhail NS, Weisdorf DJ, Wagner JE, Defor TE, Brunstein CG, Burns LJ. Comparable results of umbilical cord blood and HLA-matched sibling donor hematopoietic stem cell transplantation after reduced-intensity preparative regimen for advanced Hodgkin lymphoma. Blood. 2006;107:3804–3807.

    CAS  PubMed  Google Scholar 

  8. 8.

    Watanabe M, Kanda J, Arai Y, Hishizawa M, Nishikori M, Ishikawa T, et al. Impact of donor source on allogeneic hematopoietic stem cell transplantation for mature t cell and natural killer cell neoplasms in the kyoto stem cell transplantation group. Biol Blood Marrow Transpl. 2020;26:2346–2358.

    CAS  Google Scholar 

  9. 9.

    Zhang L, Zhang YZ. Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status. Cancer Biol Med. 2013;10:1–9.

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Ghosh N, Ahmed S, Litovich C, Woo Ahn K, Khanal M, Kharfan-Dabaja MA, et al. Comparison of reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in non-Hodgkin lymphomas (NHL)-a Center for International Blood & Marrow Transplant Research (CIBMTR) analysis. Blood. 2019;134:319–319.

    Google Scholar 

  11. 11.

    Kekre N, Marquez-Malaver FJ, Cabrero M, Pinana J, Esquirol A, Soiffer RJ, et al. Fludarabine/busulfan versus fludarabine/melphalan conditioning in patients undergoing reduced-intensity conditioning hematopoietic stem cell transplantation for lymphoma. Biol Blood Marrow Transpl. 2016;22:1808–1815.

    CAS  Google Scholar 

  12. 12.

    Imahashi N, Terakura S, Kondo E, Kako S, Uchida N, Kobayashi H, et al. Comparison of reduced-intensity/toxicity conditioning regimens for umbilical cord blood transplantation for lymphoid malignancies. Bone Marrow Transpl. 2020;55:2098–2108.

    CAS  Google Scholar 

  13. 13.

    Kanate AS, Mussetti A, Kharfan-Dabaja MA, Ahn KW, DiGilio A, Beitinjaneh A, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors. Blood. 2016;127:938–947.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Ghosh N, Karmali R, Rocha V, Ahn KW, DiGilio A, Hari PN, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: a center for International Blood and Marrow Transplant Research Analysis. J Clin Oncol. 2016;34:3141–3149.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    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;86:269–274.

    PubMed  Google Scholar 

  16. 16.

    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.

    PubMed  Google Scholar 

  17. 17.

    Kanda J. Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation. Int J Hematol. 2016;103:11–19.

    CAS  PubMed  Google Scholar 

  18. 18.

    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;15:825–828.

    CAS  Google Scholar 

  19. 19.

    Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB, et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood. 1981;57:267–276.

    CAS  PubMed  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 Transpl. 2009;15:367–369.

    Google Scholar 

  21. 21.

    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.

    CAS  PubMed  Google Scholar 

  22. 22.

    Scrucca L, Santucci A, Aversa F. Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transpl. 2007;40:381–387.

    CAS  Google Scholar 

  23. 23.

    Klein JP, Rizzo JD, Zhang MJ, Keiding N. Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis. Bone Marrow Transpl. 2001;28:909–915.

    CAS  Google Scholar 

  24. 24.

    Cox DR. Regression models and life-tables. J R Stat Soc Ser B. 1972;34:187–220.

    Google Scholar 

  25. 25.

    Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.

    Google Scholar 

  26. 26.

    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–458.

    CAS  Google Scholar 

  27. 27.

    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;123:3664–3671.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Konuma T, Tsukada N, Kanda J, Uchida N, Ohno Y, Miyakoshi S, et al. Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older. Am J Hematol. 2016;91:E284–292.

    PubMed  Google Scholar 

  29. 29.

    Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J, et al. Comparison of outcomes of 8/8 and 7/8 allele-matched unrelated bone marrow transplantation and single-unit cord blood transplantation in adults with acute leukemia. Biol Blood Marrow Transpl. 2016;22:330–338.

    Google Scholar 

  30. 30.

    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;4:2227–2235.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    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;375:944–953.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Terakura S, Kuwatsuka Y, Yamasaki S, Wake A, Kanda J, Inamoto Y, et al. GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia. Bone Marrow Transpl. 2017;52:1261–1267.

    CAS  Google Scholar 

  33. 33.

    Terakura S, Wake A, Inamoto Y, Murata M, Sakai R, Yamaguchi T, et al. Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil. Bone Marrow Transpl. 2017;52:423–430.

    CAS  Google Scholar 

  34. 34.

    Fatobene G, Rocha V, St Martin A, Hamadani M, Robinson S, Bashey A, et al. Nonmyeloablative alternative donor transplantation for Hodgkin and non-Hodgkin lymphoma: from the LWP-EBMT, Eurocord, and CIBMTR. J Clin Oncol. 2020;38:1518–1526.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Fuchs EJ, O’Donnell PV, Eapen M, Logan B, Antin JH, Dawson P, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137:420–428.

    CAS  PubMed  Google Scholar 

  36. 36.

    Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, et al. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transpl. 2014;20:1573–1579.

    Google Scholar 

  37. 37.

    Giannotti F, Labopin M, Shouval R, Sanz J, Arcese W, Angelucci E, et al. Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine. J Hematol Oncol. 2018;11:110.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Baron F, Ruggeri A, Beohou E, Labopin M, Mohty M, Sanz J, et al. Occurrence of graft-versus-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT. J Intern Med. 2018;283:178–189.

    CAS  PubMed  Google Scholar 

  39. 39.

    Chen YB, Wang T, Hemmer MT, Brady C, Couriel DR, Alousi A, et al. GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes. Bone Marrow Transpl. 2017;52:400–408.

    Google Scholar 

  40. 40.

    Kanda J, Morishima Y, Terakura S, Wake A, Uchida N, Takahashi S, et al. Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation. Leukemia. 2017;31:663–668.

    CAS  PubMed  Google Scholar 

  41. 41.

    Preussler JM, Denzen EM, Majhail NS. Costs and cost-effectiveness of hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2012;18:1620–1628.

    Google Scholar 

Download references

Acknowledgements

We thank all staff members of the collaborating institutions of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) and all the members of the data management committees of the JSHCT. This work was supported in part in part by a Grant-in-Aid for Scientific Research (KAKENHI 19K17854 to NI) from the Japan Society for the Promotion of Science (JSPS) and the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED, under grant number 19ek0510023h0002.

Author information

Affiliations

Authors

Contributions

NI designed the research, analyzed the data, and wrote the manuscript. ST, EK, K. Kato, SWK, AS, MW, and JK analyzed the data and helped write the manuscript. TF, NU, HK, JI, K. Kataoka, SS, T. Ikeda, KM, TE, and T. Kondo collected the patient data. T. Kimura, MO, T. Ichinohe, and YA supervised the data management. JK and EK designed and supervised the research. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Nobuhiko Imahashi.

Ethics declarations

Competing interests

EK received speaker honoraria from Sumitomo Dainippon Pharma Co. and Takeda Pharmaceutical Co. T. Ichinohe has received speaker honoraria from Bristol-Myers Squibb, Celgene, Janssen Pharmaceutical K.K., and Kyowa Kirin Co. and research funding from Astellas Pharma, Chugai Pharmaceutical Co., CSL Behring, Eisai Co., FUJIFILM Wako Chemicals., Kyowa Kirin Co., Ono Pharmaceutical Co., Pfizer, Nippon Shinyaku Co., MSD, Otsuka Pharmaceutical Co., Repertoire Genesis Inc., Sumitomo Dainippon Pharma Co., Taiho Pharmaceutical Co., Takara Bio Inc., Takeda Pharmaceutical Co., and Zenyaku Kogyo Co. The other authors declare no competing interests.

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

Imahashi, N., Terakura, S., Kondo, E. et al. Impact of donor types on reduced-intensity conditioning allogeneic stem cell transplant for mature lymphoid malignancies. Bone Marrow Transplant (2021). https://doi.org/10.1038/s41409-021-01525-1

Download citation

Search

Quick links