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:

Comparable outcomes of haploidentical transplant with TBF conditioning versus matched unrelated donor with fludarabine/busulfan conditioning for acute myeloid leukemia

Bone Marrow Transplantation volume 56, pages 622–634 (2021)Cite this article

Subjects

Abstract

We compared transplant outcomes of 708 acute myeloid leukemia (AML) patients receiving haploidentical allogeneic hematopoietic-cell transplantation using thiotepa/busulfan/fludarabine (TBF) conditioning with posttransplant cyclophosphamide (ptCy), to 2083 patients receiving matched unrelated donor (MUD) transplantation using fludarabine/busulfan (FB) conditioning and in vivo T-cell depletion. For intermediate cytogenetic risk AML transplanted in first complete remission (CR1), multivariate analysis revealed that haplo-TBF significantly increased nonrelapse mortality (NRM) (HR 2.1; p = 0.0006) but did not affect relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), or graft-versus-host disease-free, relapse-free survival (GRFS). For high cytogenetic risk AML transplanted in CR1, haplo-TBF significantly increased NRM (HR = 2.7; p = 0.02), decreased RI (HR = 0.45; p = 0.03) but had no influence on LFS, OS, or GRFS. For AML transplanted in CR2, haplo-TBF significantly increased NRM (HR = 2.36; p = 0.008), decreased RI (HR = 0.38; p = 0.005), but had no influence on LFS, OS, or GRFS. Finally, for AML patients transplanted with active disease, haplo-TBF had no influence on transplant outcomes. In conclusion, compared to MUD-FB, haplo-TBF increased NRM, reduced RI in high-risk AML in CR, resulting in similar LFS, OS, and GRFS. These results comparing two different approaches support the use of a haploidentical family donor for high-risk AML patients lacking a matched sibling donor.

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: Transplant outcomes for intermediate-risk AML patients transplanted in CR1.
Fig. 2: Transplant outcomes for high-risk AML patients transplanted in CR1.
Fig. 3: Transplant outcomes for AML patients transplanted in CR2.
Fig. 4: Transplant outcomes for AML patients transplanted with active disease.

Similar content being viewed by others

References

  1. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.

    Article  Google Scholar 

  2. Gupta V, Tallman MS, He W, Logan BR, Copelan E, Gale RP, et al. Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis. Blood. 2010;116:1839–48.

    Article  CAS  Google Scholar 

  3. Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the US registry. N Engl J Med. 2014;371:339–48.

    Article  CAS  Google Scholar 

  4. 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. https://doi.org/10.1016/j.bbmt.2008.03.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Luznik L, Bolaños-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, et al. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010;115:3224–30.

    Article  CAS  Google Scholar 

  6. Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:10.

    Article  CAS  Google Scholar 

  7. Kanakry JA, Luznik L. Might haplo “be the (better) match”? Blood. 2016;127:799–800.

    Article  CAS  Google Scholar 

  8. Ciurea SO, Zhang M-J, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–40.

    Article  CAS  Google Scholar 

  9. Lorentino F, Labopin M, Bernardi M, Ciceri F, Socié G, Cornelissen JJ, et al. Comparable outcomes of haploidentical, 10/10 and 9/10 unrelated donor transplantation in adverse karyotype AML in first complete remission. Am J Hematol. 2018;93:1236–44.

    Article  Google Scholar 

  10. Pagliardini T, Harbi S, Fürst S, Castagna L, Legrand F, Faucher C, et al. Post-transplantation cyclophosphamide-based haploidentical versus Atg-based unrelated donor allogeneic stem cell transplantation for patients younger than 60 years with hematological malignancies: a single-center experience of 209 patients. Bone Marrow Transplant. 2019;54:1067–76.

    Article  CAS  Google Scholar 

  11. Bazarbachi A, Boumendil A, Finel H, Castagna L, Dominietto A, Blaise D, et al. Influence of donor type, stem cell source and conditioning on outcomes after haploidentical transplant for lymphoma–a LWP‐EBMT study. Br J Haematol. 2019;188:745–56.

    Article  Google Scholar 

  12. Gu B, Zhang X, Chen G, Wu X, Ma X, Chen S, et al. Efficacy of haploidentical hematopoietic stem cell transplantation compared to HLA-matched transplantation for primary refractory acute myeloid leukemia. Ann Hematol. 2018;97:2185–94.

    Article  CAS  Google Scholar 

  13. Gagelmann N, Bacigalupo A, Rambaldi A, Hoelzer D, Halter J, Sanz J, et al. Haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy vs other donor transplantations in adults with hematologic cancers: a systematic review and meta-analysis. JAMA Oncol. 2019;5:1739–48.

    Article  Google Scholar 

  14. Arcuri LJ, Aguiar MTM, Ribeiro AAF, Pacheco AGF. Haploidentical transplantation with post-transplant cyclophosphamide versus unrelated donor hematopoietic stem cell transplantation: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2019;25:2422–30.

    Article  CAS  Google Scholar 

  15. Yang B, Yu R, Cai L, Guo B, Chen H, Zhang H, et al. Haploidentical versus matched donor stem cell transplantation for patients with hematological malignancies: a systemic review and meta-analysis. Bone Marrow Transplant. 2019;54:99–122.

    Article  CAS  Google Scholar 

  16. Passweg J, Baldomero H, Bader P, Bonini C, Duarte R, 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 Transplant. 2017;52:811–7.

    Article  CAS  Google Scholar 

  17. Perales M-A, Tomlinson B, Zhang M-J, Martin AS, Beitinjaneh A, Gibson J, et al. Alternative donor transplantation for acute myeloid leukemia in patients aged ≥50 years: young HLA-matched unrelated or haploidentical donor? Haematologica. 2020;105:407–13.

    Article  CAS  Google Scholar 

  18. Salvatore D, Labopin M, Ruggeri A, Battipaglia G, Ghavamzadeh A, Ciceri F, et al. Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2018;103:1317–28.

    Article  CAS  Google Scholar 

  19. Solomon SR, St. Martin A, Shah NN, Fatobene G, Al Malki MM, Ballen KK, et al. Myeloablative vs reduced intensity T-cell–replete haploidentical transplantation for hematologic malignancy. Blood Adv. 2019;3:2836–44.

    Article  Google Scholar 

  20. Kasamon YL, Bolaños-Meade J, Prince GT, Tsai H-L, McCurdy SR, Kanakry JA, et al. Outcomes of nonmyeloablative HLA-haploidentical blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in older adults. J Clin Oncol. 2015;33:3152.

    Article  CAS  Google Scholar 

  21. 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 Transplant. 2013;19:117–22.

    Article  CAS  Google Scholar 

  22. Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transplant. 2015;50:S37–9.

    Article  CAS  Google Scholar 

  23. Pagliardini T, Castagna L, Harbi S, Della Porta M, Rey J, Fürst S, et al. Thiotepa, fludarabine, and busulfan conditioning regimen before T cell-replete haploidentical transplantation with post-transplant cyclophosphamide for acute myeloid leukemia: a bicentric experience of 100 patients. Biol Blood Marrow Transplant. 2019;25:1803–9.

    Article  CAS  Google Scholar 

  24. Duléry R, Bastos J, Paviglianiti A, Malard F, Brissot E, Battipaglia G, et al. Thiotepa, busulfan, and fludarabine conditioning regimen in T cell-replete HLA-haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:1407–15.

    Article  Google Scholar 

  25. Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015;16:1525–36.

    Article  CAS  Google Scholar 

  26. 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  Google Scholar 

  27. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304. https://doi.org/10.1097/00007890-197410000-00001.

    Article  CAS  PubMed  Google Scholar 

  28. Terwey TH, Vega-Ruiz A, Hemmati PG, Martus P, Dietz E, le Coutre P, et al. NIH-defined graft-versus-host disease after reduced intensity or myeloablative conditioning in patients with acute myeloid leukemia. Leukemia. 2012;26:536–42. https://doi.org/10.1038/leu.2011.230.

    Article  CAS  PubMed  Google Scholar 

  29. R Core Team. R: a language for statistical computing. 2014. Vienna, Austria: R Foundation for Statistical Computing. 2018.

  30. Salas MQ, Law AD, Lam W, Al-Shaibani Z, Loach D, Michelis FV, et al. Safety and efficacy of haploidentical peripheral blood stem cell transplantation for myeloid malignancies using post-transplantation cyclophosphamide and anti-thymocyte globulin as graft-versus-host disease prophylaxis. Clin Hematol Int. 2019;1:105–13.

    Google Scholar 

  31. Saraceni F, Labopin M, Hamladji R-M, Mufti G, Socié G, Shimoni A, et al. Thiotepa-busulfan-fludarabine compared to busulfan-fludarabine for sibling and unrelated donor transplant in acute myeloid leukemia in first remission. Oncotarget. 2018;9:3379.

    Article  Google Scholar 

  32. El-Cheikh J, Labopin M, Al-Chami F, Bazarbachi A, Angelucci E, Santarone S, et al. Effect of the thiotepa dose in the TBF conditioning regimen in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia in complete remission: a report From the EBMT Acute Leukemia Working Party. Clin Lymphoma Myeloma Leuk. 2020;20:296–304.

    Article  Google Scholar 

  33. Shimoni A, Labopin M, Finke J, Ciceri F, Deconinck E, Kröger N, et al. Donor selection for a second allogeneic stem cell transplantation in AML patients relapsing after a first transplant: a study of the Acute Leukemia Working Party of EBMT. Blood Cancer J. 2019;9:1–9.

    Article  Google Scholar 

  34. Roy DC, Walker I, Maertens J, Lewalle P, Olavarria E, Selleslag D, et al. ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia. Leukemia. 2020;34:1–17.

    Article  Google Scholar 

Download references

Acknowledgements

AB and MM proposed the study, interpreted the data, and wrote the manuscript. ML helped with the design and was responsible for statistical analysis. All other authors reported updated patient data and read and commented on the manuscript. All authors proofread the manuscript and agreed on the data presented.

Author information

Authors and Affiliations

  1. Bone Marrow Transplant Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Ali Bazarbachi & Jean El Cheikh

  2. Department of Haematology and EBMT Paris Study Office/CEREST-TC, Saint Antoine Hospital, INSERM UMR 938, Université Pierre et Marie Curie, Paris, France

    Myriam Labopin & Mohamad Mohty

  3. Programme de Transplantation & Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France

    Didier Blaise

  4. CHU Bordeaux, service d’hematologie et therapie Cellulaire, F-33000, Bordeaux, France

    Edouard Forcade

  5. Department of Hematology—BMT, Hopital St. Louis, Paris, France

    Gerard Socié

  6. Service d’Hématologie, Hopital Jean Minjoz, Besancon, France

    Ana Berceanu

  7. Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Emanuele Angelucci

  8. Service d’Hématologie, CHU Grenoble Alpes—Université Grenoble Alpes, Grenoble, France

    Claude Eric Bulabois

  9. Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  10. Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

    Alessandro Rambaldi

  11. Département d’Hématologie Clinique, 11 CHU Saint Eloi, Unité de Greffes Hématologiques, Montpellier, France

    Patrice Ceballos

  12. Department of Laboratory Medicine, CAST, Karolinska Institutet and University Hospital, Stockholm, Sweden

    Stephan Mielke

  13. CHU Lille, Univ Lille, INSERM, Infinite, U1286, F-59000, Lille, France

    Ibrahim Yakoub-Agha

  14. Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin Savani

  15. Department of Internal Medicine, BMT Unit, University Hospital of Patras, Patras, Greece

    Alexandros Spyridonidis

  16. Chaim Sheba Medical Center, Tel Aviv University, Tel HaShomer, Israel

    Arnon Nagler

Authors
  1. Ali Bazarbachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myriam Labopin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Didier Blaise
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edouard Forcade
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gerard Socié
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Berceanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Emanuele Angelucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Claude Eric Bulabois
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nicolaus Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alessandro Rambaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Patrice Ceballos
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Stephan Mielke
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jean El Cheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ibrahim Yakoub-Agha
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Bipin Savani
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Alexandros Spyridonidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Arnon Nagler
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Mohamad Mohty
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ali Bazarbachi or Mohamad Mohty.

Ethics declarations

Conflict of interest

AB received honorarium from Jazz, Adienne, and Sanofi. MM received honorarium from Jazz, Riemser, and Sanofi. EA reports personal fees from Novartis, Jazz Pharmaceuticals, Bluebird Bio, Roche, Celgene, Vertex Pharmaceuticals, and CRISPR Therapeutics all outside the submitted work. All remaining authors do not have any conflicts 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

Bazarbachi, A., Labopin, M., Blaise, D. et al. Comparable outcomes of haploidentical transplant with TBF conditioning versus matched unrelated donor with fludarabine/busulfan conditioning for acute myeloid leukemia. Bone Marrow Transplant 56, 622–634 (2021). https://doi.org/10.1038/s41409-020-01074-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-01074-z

This article is cited by

Search

Advanced search

Quick links