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:

Second haploidentical stem cell transplantation for primary graft failure

Bone Marrow Transplantation volume 56, pages 1291–1296 (2021)Cite this article

Subjects

Abstract

We report the outcome of 19 patients who experienced primary graft failure (PrGF) after a haploidentical (HAPLO), unmanipulated bone marrow transplant. The median age of patients was 52 years; the conditioning regimen of the first HAPLO transplant was either full dose total body irradiation (TBI) or fludarabine, busulfan, and thiotepa (TBF); PTCY was given to all patients together with cyclosporine and mycophenolate. All 19 patients with PrGF received a second HAPLO graft, at a median interval of 42 days (34–82) after HSCT, using the Baltimore protocol and G-CSF mobilized PB from the same (n = 13) or another HAPLO family donor (n = 6). GvHD prophylaxis was again PTCY-based; 14/19 patients had trilineage recovery (74%) and 1-year survival was 66%. Engraftment at second HAPLO was seen in 7/8 patient with, and in 5/7 patients without donor-specific antibodies (DSA). In a multivariate logistic regression analysis on the original group of 503 patients, there was a trend for a reduced dose of busulfan, to increase the risk of PrGF (p = 0.1). In conclusion, patients with PrGF following a HAPLO transplant, can be rescued with a second early HAPLO transplant, using the same or a different donor.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: 1-years OS in patients with PrGF.

Similar content being viewed by others

References

  1. Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transpl. 2017;52:811–7.

    Article  CAS  Google Scholar 

  2. 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 Transpl. 2008;14:641–50.

    Article  CAS  Google Scholar 

  3. Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood. 2006;107:3065–73.

    Article  CAS  Google Scholar 

  4. Locatelli F, Bauquet A, Palumbo, Moretta F, Bertaina A. Negative depletion of α/β+ T cells and of CD19+ B lymphocytes: a novel frontier to optimize the effect of innate immunity in HLA-mismatched hematopoietic stem cell transplantation. Immunol Lett. 2013;155:21–3.

    Article  CAS  Google Scholar 

  5. Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, et al. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood. 2014;124(Aug):843–50. 7

    Article  CAS  Google Scholar 

  6. McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolaños-Meade J, Rosner GL, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125:3024–31.

    Article  CAS  Google Scholar 

  7. Ozdemir ZN, Bozdağ SC. Graft failure after allogeneic hematopoietic stem cell transplantation. Transfus Apheresis Sci. 2018;57:163–7.

    Article  Google Scholar 

  8. 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  Google Scholar 

  9. Stasia A, Ghiso A, Galaverna F, Raiola AM, Gualandi F, Luchetti S, et al. CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation. Biol Blood Marrow Transpl. 2014;20:1440–3.

    Article  CAS  Google Scholar 

  10. Nakamura H, Gress RE. Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow. Transplantation. 1990;49:453–8.

    Article  CAS  Google Scholar 

  11. Kernan NA, Flomenberg N, Dupont B, O’Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA- non identical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987;43:842–7.

    Article  CAS  Google Scholar 

  12. 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 Transpl. 2015;21:1392–8.

    Article  CAS  Google Scholar 

  13. Ciurea SO, de Lima M, Cano, Korbling M, Giralt S, Shpall EJ, et al. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation. Transplantation. 2009;88:1019–24. 27

    Article  CAS  Google Scholar 

  14. Yoshihara S, Maruya E, Taniguchi K, Kaida K, Kato R, Inoue T, et al. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT. Bone Marrow Transpl. 2012;47:508–15.

    Article  CAS  Google Scholar 

  15. Chang YJ, Zhao XY, Xu LP, Zhang XH, Wang Y, Han W, et al. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets. J Hematol Oncol. 2015;10:84.

    Article  Google Scholar 

  16. Takanashi M, Atsuta Y, Fujiwara K, Kodo H, Kai S, Sato H, et al. The impact of anti-HLA antibodies on unrelated cord blood transplantations. Blood. 2010;116:2839–46.

    Article  CAS  Google Scholar 

  17. Ruggeri A, Rocha V, Masson E, Labopin M, Cunha R, Absi L, et al. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d’Histocompatibilité et d’Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis. Haematologica. 2013;98:1154–60.

    Article  Google Scholar 

  18. Bramanti S, Calafiore V, Longhi E, Mariotti J, Crespiatico L, Sarina B, et al. Donor-specific anti-HLA antibodies in haploidentical stem cell transplantation with post-transplantation cyclophosphamide: risk of graft failure, poor graft function, and impact on outcomes. Biol Blood Marrow Transpl. 2019;25:1395–46.

  19. 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 Transpl. 2019;25:1798–802.

  20. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transpl. 2013;19:117–22.

    Article  CAS  Google Scholar 

  21. Lion T, Watzinger F, Preuner S, Kreyenberg H, Tilanus M, de Weger R, et al. The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation. Leukemia. 2012;26:1821–8.

    Article  CAS  Google Scholar 

  22. Fuchs EJ. HLA-haploidentical blood or marrow transplantation with high-dose, post-transplantation cyclophosphamide. Bone Marrow Transpl. 2015;50 Suppl 2:S31–6.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  24. Ruggeri A, Labopin M, Bacigalupo A, Gülbas 4, Koc Y, Blaise D, et al. Bone marrow versus mobilized peripheral blood stem cells, in haploidentical transplants, using post-transplant cyclophosphamide. Cancer. 2018;124:1428–37.

    Article  CAS  Google Scholar 

  25. Bashey A, Zhang MJ, McCurdy SR, St Martin A, Argall T, Anasetti C, et al. Mobilized peripheral blood stem cells versus unstimulated bone marrow as a graft source for T-cell–replete haploidentical donor transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2017;35:3002–9.

    Article  CAS  Google Scholar 

  26. Remberger M, Watz E, Ringdén O, Mattsson J, Shanwell A, Wikman A. Major ABO blood group mismatch increases the risk for graft failure after unrelated donor hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2007;13:675–82.

    Article  Google Scholar 

  27. Canaani J, Savani BN, Labopin M, Huang XJ, Ciceri F, Arcese W, et al. Impact of ABO incompatibility on patients’ outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia—a report from the Acute Leukemia Working Party of the EBMT. Haematologica. 2017;102:1066–74.

    Article  CAS  Google Scholar 

  28. Rondón 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 Transpl. 2008;14:859–66.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by AIRC, Milano, Grant to AB.

Author information

Authors and Affiliations

  1. Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

    Sabrina Giammarco, Patrizia Chiusolo, Federica Sora, Simona Sica, Luca Laurenti, Elisabetta Metafuni, Idanna Innocenti, Francesco Autore & Andrea Bacigalupo

  2. IRCCS Policlinico San Martino IST, Genova, Italy

    Anna Maria Raiola, Carmen Di Grazia, Stefania Bregante, Francesca Gualandi, Riccardo Varaldo & Emanuele Angelucci

  3. Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Roma, Italy

    Patrizia Chiusolo, Federica Sora, Simona Sica, Luca Laurenti & Andrea Bacigalupo

  4. Italian Bone Marrow Donor Registry (IBMDR), Ospedale Galliera, Genova, Italy

    Barbara Murgia

Authors
  1. Sabrina Giammarco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Maria Raiola
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carmen Di Grazia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefania Bregante
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesca Gualandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Riccardo Varaldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Patrizia Chiusolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Federica Sora
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Simona Sica
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luca Laurenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Elisabetta Metafuni
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Idanna Innocenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Francesco Autore
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Barbara Murgia
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Andrea Bacigalupo
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Emanuele Angelucci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sabrina Giammarco.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giammarco, S., Raiola, A.M., Di Grazia, C. et al. Second haploidentical stem cell transplantation for primary graft failure. Bone Marrow Transplant 56, 1291–1296 (2021). https://doi.org/10.1038/s41409-020-01183-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-01183-9

This article is cited by

Search

Advanced search

Quick links