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Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplantation volume 57, pages 399–406 (2022)Cite this article

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Abstract

Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119). Patients transplanted either in complete remission (CR) or with active disease were included in the analysis. The characteristics of both groups were comparable except for patients treated with TBF were older. In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%, p = 0.03). There was a tendency towards reduced incidence of relapse after TBF (p = 0.11). Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49, p = 0.03). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34, p = 0.009) but an increased risk of relapse (HR = 2.59, p = 0.01) without significant effect on survival and graft-versus-host disease. We conclude that for haplo-HCT recipients with ALL, Flu-TBI may be preferable for individuals at high risk of NRM while TBF should be considered in cases at high risk of relapse.

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Fig. 1: Transplantation outcomes in the Flu-TBI and TBF cohorts.

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Author information

Authors and Affiliations

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

    Ryszard Swoboda & Sebastian Giebel

  2. EBMT Paris study office; Department of Haematology, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France

    Myriam Labopin

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

    Emanuele Angelucci

  4. Nightingale Sisli Hospital, Hematopoietic SCT Unit, Istanbul, Turkey

    Mutlu Arat

  5. King Faisal Specialist Hospital & Research Centre Oncology (Section of Adult Haematolgy/BMT), Riyadh, Saudi Arabia

    Mahmoud Aljurf

  6. Universita Cattolica S. Cuore, Istituto di Ematologia, Ematologia, Rome, Italy

    Simona Sica

  7. Centre for Haematology, Imperial College London, Hammersmith Hospital, London, United Kingdom

    Jiri Pavlu

  8. Hopital St. Louis, Dept. of Hematology – BMT, Paris, France

    Gerard Socié

  9. BMT unit, Clinica Ematologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Paolo Bernasconi

  10. Ospedale S. Camillo-Forlanini, Dept. of Hematology and BMT, Rome, Italy

    Luigi Rigacci

  11. Klinikum Grosshadern, Med. Klinik III, Munich, Germany

    Johanna Tischer

  12. University of Napoli, ‘Federico II‘ Medical School, Division of Hematology, Napoli, Italy

    Antonio Risitano

  13. Hospital Clinic, Institute of Hematology & Oncology, Dept. of Hematology, Barcelona, Spain

    Montserrat Rovira

  14. Azienda Ospedaliera Universitaria Careggi, Cell Therapy and Transfusion Medicine Unit, Firenze, Italy

    Riccardo Saccardi

  15. Ospedale San Gerardo, Clinica Ematologica dell’Universita Milano-Biocca, Monza, Italy

    Pietro Pioltelli

  16. University Hospital Maastricht, Dept. Internal Med.Hematology /Oncology, Maastricht, The Netherlands

    Gwendolyn Van Gorkom

  17. Institute of Hematology and Blood Transfusion, Servicio de Hematología, Prague, Czech Republic

    Antonin Vitek

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

    Bipin N. Savani

  19. BMT Unit, University Hospital of Patras, Patras, Greece

    Alexandros Spyridonidis

  20. Department of Internal Medicine, University of Zagreb School of Medicine, Zagreb, Croatia

    Zinaida Peric

  21. Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Aviv University, Ramat-Gan, Israel

    Arnon Nagler

  22. Hôpital Saint-Antoine, Paris, France

    Mohamad Mohty

Authors
  1. Ryszard Swoboda
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Contributions

SG designed the study. SG and R Swoboda interpreted the data, and wrote the manuscript draft and final version. ML performed the statistical analysis. EA, M Arat, M Aljurf, SS, JP, GS, PB, LR, JT, AR, MR, R Saccardi, PP, GVH, AV, BNS, AS, ZP, AN and MM provided patient data. ML, EA, MA, MA, SS, JP, GS, PB, LR, JT, AR, MR, RS, PP, GVH, AV, BNS, AS, ZP, AN and MM contributed to the manuscript and critically reviewed the final version.

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Correspondence to Ryszard Swoboda.

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Swoboda, R., Labopin, M., Giebel, S. et al. Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant 57, 399–406 (2022). https://doi.org/10.1038/s41409-021-01550-0

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