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Comparing outcomes of a second allogeneic hematopoietic cell transplant using HLA-matched unrelated versus T-cell replete haploidentical donors in relapsed acute lymphoblastic leukemia: a study of the Acute Leukemia Working Party of EBMT

Bone Marrow Transplantation volume 56, pages 2194–2202 (2021)Cite this article

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Abstract

Optimal donor choice for a second allogeneic hematopoietic cell transplant (allo-HCT) in relapsed acute lymphoblastic leukemia (ALL) remains undefined. We compared outcomes using HLA-matched unrelated donors (MUD) versus haploidentical donors in this population. Primary endpoint was overall survival (OS). The MUD allo-HCT group comprised 104 patients (male = 56, 54%), median age 36 years, mostly (76%) with B-cell phenotype in complete remission (CR) (CR2/CR3 + = 76, 73%). The 61 patients (male = 38, 62%) in the haploidentical group were younger, median age 30 years (p = 0.002), had mostly (79%) a B-cell phenotype and the majority were also in CR at time of the second allo-HCT (CR2/CR3 + = 40, 66%). Peripheral blood stem cells was the most common cell source in both, but a significantly higher number in the haploidentical group received bone marrow cells (26% vs. 4%, p < 0.0001). A haploidentical donor second allo-HCT had a 1.5-fold higher 2-year OS (49% vs. 31%), albeit not statistically significant (p = 0.13). A longer time from first allo-HCT to relapse was associated with improved OS, leukemia-free survival, graft-versus-host disease-free-relapse-free survival, and lower cumulative incidences of relapse and non-relapse mortality. Results suggest no major OS difference when choosing either a MUD or haploidentical donor for ALL patients needing a second allo-HCT.

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Fig. 1: Survival outcomes.
Fig. 2: Relapse and nonrelapse mortality.

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Authors and Affiliations

  1. Division of Hematology-Oncology and Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL, USA

    Mohamed A. Kharfan-Dabaja

  2. Department of Hematology, Hôpital Saint Antoine, Sorbonne University and INSERM UMRs 938, Paris, France

    Myriam Labopin, Eolia Brissot & Mohamad Mohty

  3. Division of Hematology-Oncology, American University of Beirut, Beirut, Lebanon

    Ali Bazarbachi

  4. Ospedale San Raffaele s.r.l. Haematology and BMT, Milano, Italy

    Fabio Ciceri

  5. University of Freiburg, Department of Medicine-Hematology/Oncology, Freiburg, Germany

    Jürgen Finke

  6. S.S.C.V.D Trapianto di Cellule Staminali, A.O.U Citta della Salute e della Scienza di Torino, Torino, Italy

    Benedetto Bruno

  7. Universitaetsklinikum Dresden, Medizinische Klinik und Poliklinik I, Dresden, TU, Dresden, Germany

    Martin Bornhäuser

  8. Oslo University Hospital, Rikshospitalet, Clinic for Cancer Medicine, Hematology Dept.,Section for Stem Cell Transplantation, Oslo, Norway

    Tobias Gedde-Dahl

  9. Hopital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France

    Hélène Labussière-Wallet

  10. HUCH Comprehensive Cancer Center, Stem Cell Transplantation Unit, Helsinki, Finland

    Riitta Niittyvuopio

  11. University Medical Center Schleswig-Holstein, Section for Stem Cell Transplantation and Immunotherapy, Kiel, Germany

    Thomas Valerius

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

    Emanuele Angelucci

  13. Deutsche Klinik fuer Diagnostik, KMT Zentrum, Wiesbaden, Germany

    Arne Brecht

  14. Hospital Clínico Servicio de Hematología, Salamanca, Spain

    Dolores Caballero

  15. University Medical Centre, Dept. of Haematology, Utrecht, The Netherlands

    Jürgen Kuball

  16. Kings College Hospital, Dept. of Haematological Medicine, London, United Kingdom

    Victoria Potter

  17. Klinikum Augsburg, Medizinische Klinik, Augsburg, Germany

    Christoph Schmid

  18. LMU Klinikum, Department of Internal Medicine III, Munich, Germany

    Johanna Tischer

  19. Rambam Medical Center, Dept. of Hematology & BMT, Haifa, Israel

    Tsila Zuckerman

  20. Policlinico G.B. Rossi, Divisione di Ematologia, Unità di TMO, Verona, Italy

    Fabio Benedetti

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

    Didier Blaise

  22. Hematology Department, Hospital G.U Gregorio Marañon, Instituto de Investigación Sanitaria Gregorio Marañon, Medicina Universidad Complutense de Madrid, Madrid, Spain

    Jose Luis Diez-Martin

  23. Hematology Department, Hospital Universitari i Politècnic La Fe, Avinguda Fernando Abril Martorell, Valencia, Spain

    Jaime Sanz

  24. Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Annalisa Ruggeri

  25. Division of hematology and oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin N. Savani

  26. Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland

    Sebastian Giebel

  27. Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel

    Arnon Nagler

Authors
  1. Mohamed A. Kharfan-Dabaja
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  2. Myriam Labopin
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  3. Ali Bazarbachi
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  4. Fabio Ciceri
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  5. Jürgen Finke
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  6. Benedetto Bruno
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  9. Hélène Labussière-Wallet
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  13. Arne Brecht
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  14. Dolores Caballero
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  15. Jürgen Kuball
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  16. Victoria Potter
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  17. Christoph Schmid
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  18. Johanna Tischer
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  19. Tsila Zuckerman
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  20. Fabio Benedetti
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  21. Didier Blaise
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  23. Jaime Sanz
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  24. Annalisa Ruggeri
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  25. Eolia Brissot
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  26. Bipin N. Savani
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  27. Sebastian Giebel
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  28. Arnon Nagler
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  29. Mohamad Mohty
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Corresponding author

Correspondence to Mohamad Mohty.

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Conflict of interest

MAK-D reports consultancy for Daiichi Sankyo and Pharmacyclics; JK: reports research support from Novartis, Miltenyi Biotech and Gadeta and shareholder and scientific cofounder of Gadeta; MM: Consultancy, research funding, honoraria and speaker’s bureau for Sanofi, Janssen, Amgen, Takeda, Celgene, Glaxo Smith Kline, Jazz pharmaceuticals, Adaptive, Stemline, Bristol Myers Squibb, Novartis. The remaining authors declare no competing interests.

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Kharfan-Dabaja, M.A., Labopin, M., Bazarbachi, A. et al. Comparing outcomes of a second allogeneic hematopoietic cell transplant using HLA-matched unrelated versus T-cell replete haploidentical donors in relapsed acute lymphoblastic leukemia: a study of the Acute Leukemia Working Party of EBMT. Bone Marrow Transplant 56, 2194–2202 (2021). https://doi.org/10.1038/s41409-021-01317-7

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