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:

Comparison of the outcomes after haploidentical and cord blood salvage transplantations for graft failure following allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 1784–1795 (2020)Cite this article

Subjects

Abstract

Graft failure (GF) is a life-threatening complication after allogeneic stem cell transplantation (SCT). Although salvage SCTs can be performed with haploidentical donor (HID) or cord blood (CB), no study has compared the performances of these two sources. Using nationwide registration data, we compared the transplant outcomes of patients who developed GF and underwent salvage transplantation from HID (n = 129) and CB (n = 570) from 2007 to 2016. The HID group demonstrated better neutrophil recovery (79.7 vs. 52.5% at 30 days, P < 0.001). With a median follow-up of 3 years, both groups demonstrated similar overall survival (OS) and nonrelapse mortality (NRM; 1-year OS, 33.1 vs. 34.6% and 1-year NRM, 45.1 vs. 49.8% for the HID and CB groups). After adjustments for other covariates, OS did not differ in both groups. However, HID was associated with a lower NRM (hazard ratio, 0.71; P = 0.038) than CB. The incidence of acute graft-versus-host disease (GVHD)-related deaths was significantly higher in the HID group, although infection-related deaths were observed more frequently in the CB group. HID may be a promising salvage SCT option after GF due to its faster engraftment and low NRM.

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: Engraftment rate after salvage transplantation.
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. nccn.org [internet]. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. Version 3. 2019. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 11 Aug.

  2. Kumar R, Bonfim C, George B. Hematopoietic cell transplantation for aplastic anemia. Curr Opin Hematol. 2017;24:509–14.

    Article  PubMed  Google Scholar 

  3. Canaani J, Beohou E, Labopin M, Ghavamzadeh A, Beelen D, Hamladji RM, et al. Trends in patient outcome over the past two decades following allogeneic stem cell transplantation for acute myeloid leukaemia: an ALWP/EBMT analysis. J Intern Med. 2019;285:407–18.

    Article  CAS  PubMed  Google Scholar 

  4. Bacigalupo A, Sormani MP, Lamparelli T, Gualandi F, Occhini D, Bregante S, et al. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation. Haematologica. 2004;89:1238–47.

    PubMed  Google Scholar 

  5. Narimatsu H, Kami M, Miyakoshi S, Murashige N, Yuji K, Hamaki T, et al. Graft failure following reduced-intensity cord blood transplantation for adult patients. Br J Haematol. 2006;132:36–41.

    Article  PubMed  Google Scholar 

  6. Olsson R, Remberger M, Schaffer M, Berggren DM, Svahn BM, Mattsson J, et al. Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transplant. 2013;48:537–43.

    Article  CAS  PubMed  Google Scholar 

  7. Olsson RF, Logan BR, Chaudhury S, Zhu X, Akpek G, Bolwell BJ, et al. Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia. 2015;29:1754–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cluzeau T, Lambert J, Raus N, Dessaux K, Absi L, Delbos F, et al. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI. Bone Marrow Transplant. 2016;51:687–91.

    Article  CAS  PubMed  Google Scholar 

  9. Sun YQ, He GL, Chang YJ, Xu LP, Zhang XH, Han W, et al. The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation. Ann Hematol. 2015;94:1699–705.

    Article  CAS  PubMed  Google Scholar 

  10. Masouridi-Levrat S, Simonetta F, Chalandon Y. Immunological basis of bone marrow failure after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;7:362.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Ozdemir ZN, Civriz Bozdağ S. Graft failure after allogeneic hematopoietic stem cell transplantation. Transfus Apher Sci. 2018;57:163–7.

    Article  PubMed  Google Scholar 

  12. Kawashima N, Terakura S, Nishiwaki S, Koyama D, Ozawa Y, Ito M, et al. Increase of bone marrow macrophages and CD8+ T lymphocytes predict graft failure after allogeneic bone marrow or cord blood transplantation. Bone Marrow Transplant. 2017;52:1164–70.

    Article  CAS  PubMed  Google Scholar 

  13. Martin PJ. Prevention of allogeneic marrow graft rejection by donor T cells that do not recognize recipient alloantigens: potential role of a veto mechanism. Blood. 1996;88:962–9.

    Article  CAS  PubMed  Google Scholar 

  14. Murphy WJ, Bennett M, Kumar V, Longo DL. Donor-type activated natural killer cells promote marrow engraftment and B cell development during allogeneic bone marrow transplantation. J Immunol. 1992;148:2953–60.

    CAS  PubMed  Google Scholar 

  15. Ciurea SO, Thall PF, Milton DR, Barnes TH, Kongtim P, Carmazzi Y, et al. Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21:1392–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kongtim P, Cao K, Ciurea SO. Donor specific Anti-HLA antibody and risk of graft failure in haploidentical stem cell transplantation. Adv Hematol. 2016;2016:4025073.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Kong Y, Wang YT, Hu Y, Han W, Chang YJ, Zhang XH, et al. The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function. Bone Marrow Transplant. 2016;51:249–55.

    Article  CAS  PubMed  Google Scholar 

  18. Selleri C, Sato T, Anderson S, Young NS, Maciejewski JP. Interferon-gamma and tumor necrosis factor-alpha suppress both early and late stages of hematopoiesis and induce programmed cell death. J Cell Physiol. 1995;165:538–46.

    Article  CAS  PubMed  Google Scholar 

  19. Merli P, Caruana I, De Vito R, Strocchio L, Weber G, Del Bufalo F, et al. Role of IFNγ in immune-mediated graft failure occurring after allogeneic hematopoietic stem cell transplantation. Haematologica. 2019. https://doi.org/10.3324/haematol.2019.216101.

  20. Alcazer V, Conrad A, Valour F, Bachy E, Salles G, Huynh A, et al. Early-onset severe infections in allogeneic hematopoietic stem cell transplantation recipients with graft failure. Am J Hematol. 2019;94:E109–11.

    Article  PubMed  Google Scholar 

  21. Schriber J, Agovi MA, Ho V, Ballen KK, Bacigalupo A, Lazarus HM, et al. Second unrelated donor hematopoietic cell transplantation for primary graft failure. Biol Blood Marrow Transplant. 2010;16:1099–106.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fuji S, Nakamura F, Hatanaka K, Taniguchi S, Sato M, Mori S, et al. Peripheral blood as a preferable source of stem cells for salvage transplantation in patients with graft failure after cord blood transplantation: a retrospective analysis of the registry data of the Japanese Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2012;18:1407–14.

    Article  PubMed  Google Scholar 

  23. Waki F, Masuoka K, Fukuda T, Kanda Y, Nakamae M, Yakushijin K, et al. Feasibility of reduced-intensity cord blood transplantation as salvage therapy for graft failure: results of a nationwide survey of adult patients. Biol Blood Marrow Transplant. 2011;17:841–51.

    Article  PubMed  Google Scholar 

  24. Onishi Y, Mori T, Kako S, Koh H, Uchida N, Kondo T, et al. Outcome of second transplantation using umbilical cord blood for graft failure after allogeneic hematopoietic stem cell transplantation for aplastic anemia. Biol Blood Marrow Transplant. 2017;23:2137–42.

    Article  PubMed  Google Scholar 

  25. Lund TC, Liegel J, Bejanyan N, Orchard PJ, Cao Q, Tolar J, et al. Second allogeneic hematopoietic cell transplantation for graft failure: poor outcomes for neutropenic graft failure. Am J Hematol. 2015;90:892–6.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Shimada K, Narimatsu H, Morishita Y, Kohno A, Saito S, Kato Y. Severe regimen-related toxicity of second transplantation for graft failure following reduced-intensity cord blood transplantation in an adult patient. Bone Marrow Transplant. 2006;37:787–8.

    Article  CAS  PubMed  Google Scholar 

  27. Davies SM, Weisdorf DJ, Haake RJ, Kersey JH, McGlave PB, Ramsay NK, et al. Second infusion of bone marrow for treatment of graft failure after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994;14:73–7.

    CAS  PubMed  Google Scholar 

  28. Rashidi A, Slade M, DiPersio JF, Westervelt P, Vij R, Romee R. Post-transplant high-dose cyclophosphamide after HLA-matched vs haploidentical hematopoietic cell transplantation for AML. Bone Marrow Transplant. 2016;51:1561–4.

    Article  CAS  PubMed  Google Scholar 

  29. Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, et al. Comparison of outcomes of hematopoietic cell transplants from T-replete haploidentical donors using post-transplantation cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors and hla-identical sibling donors: a multivariable analysis including disease risk index. Biol Blood Marrow Transplant. 2016;22:125–33.

    Article  CAS  PubMed  Google Scholar 

  30. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, et al. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood. 2015;125:3956–62.

    Article  CAS  PubMed  Google Scholar 

  31. Singh H, Nikiforow S, Li S, Ballen KK, Spitzer TR, Soiffer R, et al. Outcomes and management strategies for graft failure after umbilical cord blood transplantation. Am J Hematol. 2014;89:1097–101.

    Article  PubMed  Google Scholar 

  32. Kliman D, Bilmon I, Kwan J, Blyth E, Micklethwaite K, Panicker S, et al. Rescue haploidentical peripheral blood stem cell transplantation for engraftment failure: a single-centre case series. Intern Med J. 2018;48:988–91.

    Article  CAS  PubMed  Google Scholar 

  33. Yoshihara S, Ikegame K, Taniguchi K, Kaida K, Kim EH, Nakata J, et al. Salvage haploidentical transplantation for graft failure using reduced-intensity conditioning. Bone Marrow Transplant. 2012;47:369–73.

    Article  CAS  PubMed  Google Scholar 

  34. Moscardó F, Romero S, Sanz J, Sanz MA, Montesinos P, Lorenzo I, et al. T cell-depleted related HLA-mismatched peripheral blood stem cell transplantation as salvage therapy for graft failure after single unit unrelated donor umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2014;20:1060–3.

    Article  PubMed  CAS  Google Scholar 

  35. Tang BL, Zhu XY, Zheng CC, Liu HL, Geng LQ, Wang XB, et al. Successful early unmanipulated haploidentical transplantation with reduced-intensity conditioning for primary graft failure after cord blood transplantation in hematologic malignancy patients. Bone Marrow Transplant. 2015;50:248–52.

    Article  CAS  PubMed  Google Scholar 

  36. Prata PH, Resche-Rigon M, Blaise D, Socié G, Rohrlich PS, Milpied N, et al. Outcomes of salvage haploidentical transplant with post-transplant cyclophosphamide for rescuing graft failure patients: a report on behalf of the francophone society of bone marrow transplantation and cellular therapy. Biol Blood Marrow Transplant. 2019. https://doi.org/10.1016/j.bbmt.2019.05.013.

  37. 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  PubMed  Google Scholar 

  38. Kanda J. Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation. Int J Hematol. 2016;103:11–9.

    Article  CAS  PubMed  Google Scholar 

  39. 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  PubMed  PubMed Central  Google Scholar 

  40. Armand P, Gibson CJ, Cutler C, Ho VT, Koreth J, Alyea EP, et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood. 2012;120:905–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  42. 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 

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

    Article  CAS  PubMed  Google Scholar 

  44. Kato M, Matsumoto K, Suzuki R, Yabe H, Inoue M, Kigasawa H, et al. Salvage allogeneic hematopoietic SCT for primary graft failure in children. Bone Marrow Transplant. 2013;48:1173–8.

    Article  CAS  PubMed  Google Scholar 

  45. Ruggeri A, Sun Y, Labopin M, Bacigalupo A, Lorentino F, Arcese W, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant. Haematologica. 2017;102:401–10.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 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 Transplant. 2017;52:1261–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the physicians and staff at the transplant centers who provided the clinical data to the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. 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 under Grant Number 18ek0510023h0002.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    Kaito Harada, Makoto Onizuka & Kaito Harada

  2. Department of Hematology, Osaka International Cancer Institute, Osaka, Japan

    Shigeo Fuji & Shigeo Fuji

  3. Department of Hematology and Oncology, Dokkyo Medical University School of Medicine, Mibu, Japan

    Sachiko Seo & Sachiko Seo

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

    Junya Kanda

  5. Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan

    Toshimitsu Ueki & Toshimitsu Ueki

  6. Division of Hematology, National Defense Medical College, Tokorozawa, Japan

    Fumihiko Kimura

  7. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Koji Kato

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

    Naoyuki Uchida

  9. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan

    Kazuhiro Ikegame

  10. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan

    Ken-ichi Matsuoka

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

    Noriko Doki

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

    Toshiro Kawakita

  13. Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan

    Yasushi Onishi

  14. Clinical oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan

    Shingo Yano

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

    Takahiro Fukuda

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

    Minoko Takanashi

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

    Yoshinobu Kanda

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

  20. Department of Hematology, Oita University Hospital, Yufu, Japan

    Masao Ogata & Masao Ogata

Authors
  1. Kaito Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shigeo Fuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sachiko Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junya Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshimitsu Ueki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fumihiko Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Koji Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Naoyuki Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazuhiro Ikegame
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Makoto Onizuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ken-ichi Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Noriko Doki
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Toshiro Kawakita
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yasushi Onishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Shingo Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Takahiro Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Minoko Takanashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yoshinobu Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yoshiko Atsuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Masao Ogata
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the transplant complications working group of the Japan Society for Hematopoietic Cell Transplantation

  • Kaito Harada
  • , Shigeo Fuji
  • , Sachiko Seo
  • , Toshimitsu Ueki
  •  & Masao Ogata

Corresponding author

Correspondence to Kaito Harada.

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

Harada, K., Fuji, S., Seo, S. et al. Comparison of the outcomes after haploidentical and cord blood salvage transplantations for graft failure following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 1784–1795 (2020). https://doi.org/10.1038/s41409-020-0821-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-0821-9

This article is cited by

Search

Advanced search

Quick links