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:

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience

Bone Marrow Transplantation (2024)Cite this article

Subjects

Abstract

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33–215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8–24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9–140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

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: Outcomes of 2nd transplantation (comparison with historical group).

Similar content being viewed by others

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Kharfan-Dabaja MA, Kumar A, Ayala E, Aljurf M, Nishihori T, Marsh R, et al. Standardizing definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the American Society for Transplantation and Cellular Therapy. Transplant Cell Ther. 2021;27:642–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Alcazer V, Peffault de Latour R, Ader F, Labussiere-Wallet H. Graft failure after allogeneic hematopoietic stem cell transplantation: definition and risk factors. Bull Cancer. 2019;106:574–83.

    Article  PubMed  Google Scholar 

  4. Mattsson J, Ringden O, Storb R. Graft failure after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2008;14:165–70.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ferra C, Sanz J, Diaz-Perez MA, Morgades M, Gayoso J, Cabrera JR, et al. Outcome of graft failure after allogeneic stem cell transplant: study of 89 patients. Leuk Lymphoma. 2015;56:656–62.

    Article  PubMed  Google Scholar 

  6. Locatelli F, Lucarelli B, Merli P. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Expert Opin Pharmacother. 2014;15:23–36.

    Article  CAS  PubMed  Google Scholar 

  7. Nagler A, Labopin M, Swoboda R, Kulagin A, Velardi A, Sanz J, et al. Long-term outcome of second allogeneic hematopoietic stem cell transplantation (HSCT2) for primary graft failure in patients with acute leukemia in remission: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transpl. 2023;58:1008–16.

    Article  Google Scholar 

  8. 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;8912:1097–101.

    Article  Google Scholar 

  9. Rondon G, Saliba RM, Khouri I, Giralt S, Chan K, Jabbour E, et al. Long-term follow-up of patients who experienced graft failure postallogeneic progenitor cell transplantation. Results of a single institution analysis. Biol Blood Marrow Transplant. 2008;14:859–66.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sun Y, Xu L, Liu D, Zhang X, Wang Y, Han W, et al. Second transplantation for 22 patients with graft failure after first allogeneic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2014;35:673–7.

    PubMed  Google Scholar 

  11. Chen J, Pang A, Zhao Y, Liu L, Ma R, Wei J, et al. Primary graft failure following allogeneic hematopoietic stem cell transplantation: risk factors, treatment and outcomes. Hematology. 2022;271:293–9.

    Article  Google Scholar 

  12. 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 

  13. Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, et al. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer. 2013;119:978–85.

    Article  PubMed  Google Scholar 

  14. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–54.

    Article  PubMed  Google Scholar 

  15. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Giammarco S, Raiola AM, Di Grazia C, Bregante S, Gualandi F, Varaldo R, et al. Second haploidentical stem cell transplantation for primary graft failure. Bone Marrow Transpl. 2021;56:1291–6.

    Article  CAS  Google Scholar 

  17. Harada K, Najima Y, Kato M, Fuji S, Shinohara A, Nakamae H, et al. Outcomes of salvage haploidentical transplantation using posttransplant cyclophosphamide for graft failure following allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2022;116:744–53.

    Article  CAS  PubMed  Google Scholar 

  18. Prata PH, Resche-Rigon M, Blaise D, Socie 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;25:1798–802.

    Article  PubMed  Google Scholar 

  19. Sun YQ, Wang Y, Wang FR, Yan CH, Cheng YF, Chen YH, et al. Graft failure in patients with hematological malignancies: a successful salvage with a second transplantation from a different haploidentical donor. Front Med. 2021;8:604085.

    Article  Google Scholar 

  20. Konuma T, Harada K, Kondo T, Masuko M, Uchida N, Yano S, et al. Salvage single-unit unrelated cord blood transplantation for graft failure following initial allogeneic transplantation in adult acute myeloid leukemia: trends in outcomes over the past 20 years. Bone Marrow Transpl. 2022;57:1848–50.

    Article  Google Scholar 

  21. Harada K, Fuji S, Seo S, Kanda J, Ueki T, Kimura F, et al. Comparison of the outcomes after haploidentical and cord blood salvage transplantations for graft failure following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl. 2020;55:1784–95.

    Article  CAS  Google Scholar 

  22. Wegener D, Lang P, Paulsen F, Weidner N, Zips D, Ebinger M, et al. Immunosuppressive total nodal irradiation-based reconditioning regimens after graft rejection or graft failure in pediatric patients treated with myeloablative allogeneic hematopoietic cell transplantation. Int J Radiat Oncol Biol Phys. 2019;104:137–43.

    Article  PubMed  Google Scholar 

  23. 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 

  24. Guardiola P, Kuentz M, Garban F, Blaise D, Reiffers J, Attal M, et al. Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukaemia and aplastic anaemia. French Society of Bone Marrow Transplantation. Br J Haematol. 2000;111:292–302.

    Article  CAS  PubMed  Google Scholar 

  25. Teltschik HM, Heinzelmann F, Gruhn B, Feuchtinger T, Schlegel P, Schumm M, et al. Treatment of graft failure with TNI-based reconditioning and haploidentical stem cells in paediatric patients. Br J Haematol. 2016;175:115–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Huang XJ. Overcoming graft failure after haploidentical transplantation: is this a possibility? Best Pract Res Clin Haematol. 2021;34:101255.

    Article  CAS  PubMed  Google Scholar 

  27. Prabahran A, Koldej R, Chee L, Ritchie D. Clinical features, pathophysiology, and therapy of poor graft function post-allogeneic stem cell transplantation. Blood Adv. 2022;6:1947–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was partly supported by the National Natural Science Foundation of China (grant no. 8227010768) and the National Key Research and Development Program of China (2021YFC2500300).

Author information

Author notes

  1. These authors contributed equally: Rui Ma, Dan-Ping Zhu.

Authors and Affiliations

  1. Peking University People’s Hospital, Beijing, China

    Rui Ma, Dan-Ping Zhu, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Xiao-Dong Mo, Meng Lv, Yuan-Yuan Zhang, Yi-Fei Cheng, Chen-Hua Yan, Yu-Hong Chen, Yao Chen, Jing-Zhi Wang, Feng-Rong Wang, Ting-Ting Han, Jun Kong, Zhi-Dong Wang, Wei Han, Huan Chen, Ying-Jun Chang, Yun He, Zheng-Li Xu, Feng-Mei Zheng, Hai-Xia Fu, Kai-Yan Liu, Xiao-Jun Huang & Yu-Qian Sun

  2. Peking University Institute of Hematology, Beijing, China

    Rui Ma, Dan-Ping Zhu, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Xiao-Dong Mo, Meng Lv, Yuan-Yuan Zhang, Yi-Fei Cheng, Chen-Hua Yan, Yu-Hong Chen, Yao Chen, Jing-Zhi Wang, Feng-Rong Wang, Ting-Ting Han, Jun Kong, Zhi-Dong Wang, Wei Han, Huan Chen, Ying-Jun Chang, Yun He, Zheng-Li Xu, Feng-Mei Zheng, Hai-Xia Fu, Kai-Yan Liu, Xiao-Jun Huang & Yu-Qian Sun

  3. National Clinical Research Center for Hematologic Disease, Beijing, China

    Rui Ma, Dan-Ping Zhu, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Xiao-Dong Mo, Meng Lv, Yuan-Yuan Zhang, Yi-Fei Cheng, Chen-Hua Yan, Yu-Hong Chen, Yao Chen, Jing-Zhi Wang, Feng-Rong Wang, Ting-Ting Han, Jun Kong, Zhi-Dong Wang, Wei Han, Huan Chen, Ying-Jun Chang, Yun He, Zheng-Li Xu, Feng-Mei Zheng, Hai-Xia Fu, Kai-Yan Liu, Xiao-Jun Huang & Yu-Qian Sun

  4. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, Beijing, China

    Rui Ma, Dan-Ping Zhu, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Xiao-Dong Mo, Meng Lv, Yuan-Yuan Zhang, Yi-Fei Cheng, Chen-Hua Yan, Yu-Hong Chen, Yao Chen, Jing-Zhi Wang, Feng-Rong Wang, Ting-Ting Han, Jun Kong, Zhi-Dong Wang, Wei Han, Huan Chen, Ying-Jun Chang, Yun He, Zheng-Li Xu, Feng-Mei Zheng, Hai-Xia Fu, Kai-Yan Liu, Xiao-Jun Huang & Yu-Qian Sun

Authors
  1. Rui Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan-Ping Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao-Hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lan-Ping Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao-Dong Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Meng Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuan-Yuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yi-Fei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chen-Hua Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yu-Hong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jing-Zhi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Feng-Rong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ting-Ting Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jun Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Zhi-Dong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Wei Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Huan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Ying-Jun Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Yun He
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Zheng-Li Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Feng-Mei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Hai-Xia Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Kai-Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Xiao-Jun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Yu-Qian Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

X-JH and Y-QS contributed to the study design, and RM and Y-QS wrote the manuscript. In addition, all authors provided clinical or biological data, reviewed, and approved the manuscript.

Corresponding author

Correspondence to Yu-Qian Sun.

Ethics declarations

Competing interests

The 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

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, R., Zhu, DP., Zhang, XH. et al. Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02276-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41409-024-02276-5

Search

Advanced search

Quick links