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Total body irradiation versus thiotepa/busulfan-based conditioning regimens for myeloablative allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia

Bone Marrow Transplantation (2024)Cite this article

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Abstract

Total body irradiation (TBI)-based conditioning regimens are generally recommended for allogeneic HSCT (allo-HSCT) in patients with acute lymphoblastic leukemia (ALL). Recent evidence suggests that modern chemotherapy-based regimens may be as effective. This multicenter retrospective study compared the clinical outcomes of myeloablative allo-HSCT with thiotepa, busulfan, and cyclophosphamide/fludarabine (TTB) to TBI-based conditioning. Between 2002 to 2018, 63 and 114 patients received TTB- and TBI-based conditioning regimens, respectively. The 5-year cumulative incidence of relapse was lower in the TBI cohort compared to the TTB cohort (30% [95% CI, 22–38] versus 47% [95% CI, 36–59]; P = 0.03). Multivariate analysis identified T-ALL, Ph-negative B-ALL, and measurable residual disease associated with a higher relapse risk. The 5-year cumulative incidence of non-relapsed mortality (NRM) was significantly lower with TTB (12% [95% CI, 5–20]) compared to TBI (25% [95% CI, 18–33]) (P = 0.001). Multivariate analysis found TBI conditioning, older age, and advanced stages of ALL at transplantation associated with a higher NRM. No statistical difference was seen in overall survival (49% [95% CI, 40–58] and 46% [95% CI, 35–60]) in the TBI and TTB groups, respectively; P = 0.9). The study suggests that TTB-based conditioning may be a promising option for ALL patients undergoing allo-HSCT, as it resulted in similar OS and lower NRM than TBI-based conditioning.

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Fig. 1: Cumulative incidence of acute and chronic GVHD according to conditioning regimen.
Fig. 2: Cumulative incidence and probability of outcomes according to conditioning regimen.
Fig. 3: Influence of conditioning regimen on relapse and TRM according to MRD status.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    Elvira Mora, Juan Montoro, Aitana Balaguer, Marta Villalba, Pedro Chorao, Miguel A. Sanz & Jaime Sanz

  2. Instituto de Investigación Sanitaria La Fe, Valencia, Spain

    Elvira Mora, Juan Montoro, Aitana Balaguer, Marta Villalba, Pedro Chorao, Miguel A. Sanz & Jaime Sanz

  3. Centro de Investigación Biomédica en Red de Cáncer, Instituto Carlos III, Madrid, Spain

    Aitana Balaguer & Jaime Sanz

  4. BMT Unit. Hematology Department, ICMHO, Hospital Clínic, Institut Josep Carreras contra la leucemia, Barcelona, Spain

    Montserrat Rovira

  5. Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain

    Monica Cabrero & Ana Africa Martin

  6. Instituto de Investigación Biomedica de Salamanca-IBSAL, Salamanca, Spain

    Monica Cabrero & Ana Africa Martin

  7. Hematology Department, Hospital General Universitario Morales Meseguer, Murcia, Spain

    Inmaculada Heras & Oriana Lopez Godino

  8. Hematology Department. Institut Català d’Oncologia - Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain

    Josep-Maria Ribera & Anna Torrent

  9. Department of Medicine, Universidad Autónoma de Barcelona, Badalona, Spain

    Josep-Maria Ribera

  10. Radiation Oncology Department, ICMHO, Hospital Clínic, Barcelona, Spain

    Gabriela Antelo

  11. Department of Medicine, University of Valencia, Valencia, Spain

    Miguel A. Sanz & Jaime Sanz

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Grupo Español de Trasplante Hematopoyético (GETH)

  • Elvira Mora
  • , Juan Montoro
  • , Aitana Balaguer
  • , Montserrat Rovira
  • , Monica Cabrero
  • , Inmaculada Heras
  • , Josep-Maria Ribera
  • , Gabriela Antelo
  • , Ana Africa Martin
  • , Oriana Lopez Godino
  • , Anna Torrent
  • , Marta Villalba
  • , Pedro Chorao
  • , Miguel A. Sanz
  •  & Jaime Sanz

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EM, MAS, and JS drafted the manuscript and integrated all changes and suggestions made by the rest of authors that also reviewed the manuscript and contributed to the final draft.

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Mora, E., Montoro, J., Balaguer, A. et al. Total body irradiation versus thiotepa/busulfan-based conditioning regimens for myeloablative allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02298-z

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