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Thiotepa, busulfan and fludarabine conditioning regimen for adult patients with lymphoid malignancies undergoing allogeneic stem cell transplantation: a study on behalf of GETH-TC

Bone Marrow Transplantation volume 60, pages 795–803 (2025)Cite this article

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Abstract

The efficacy of thiotepa, busulfan, and fludarabine (TBF) conditioning in lymphoproliferative disorders remains under investigation. We analyzed outcomes in 157 patients with lymphoid malignancies who underwent a first allogeneic hematopoietic stem cell transplantation (alloHCT) following TBF conditioning. Non-relapse mortality (NRM) at 3 years reached 32%, while the cumulative incidence of relapse (CIR) was 19%. At 3 years, progression-free survival (PFS), overall survival (OS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) were 49.7%, 58.0%, and 44.2%, respectively. The cumulative incidences of grade III-IV acute GVHD at 100 days and moderate-to-severe chronic GVHD at 3 years were 8.3% and 12%, respectively. On multivariate analysis, patients receiving high-dose thiotepa (10 mg/kg) demonstrated a significantly lower CIR than those receiving low-dose thiotepa (5 mg/kg) (HR 2.95 [95% CI, 1.37–6.33], p = 0.006), with no significant effect on NRM. Female donor-to-male recipient transplants were associated with reduced OS (HR 2.0 [95% CI, 1.17–3.44], p = 0.011) and increased NRM (HR 2.43 [95% CI, 1.29–4.35], p = 0.005). TBF conditioning demonstrated a substantial anti-tumor effect, counterbalanced by elevated toxicity. Careful patient selection and effective toxicity mitigation strategies are essential to ensure individuals can tolerate TBF’s toxicity while maximizing its benefits in disease control.

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Fig. 1: Univariate outcome representation of Non-relapse mortality (NRM) and cumulative incidence of relapse (CIR).
Fig. 2: Survival outcomes.

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Data availability

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

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Acknowledgements

We thank the patients, as well as the nursing and support staff at the Hematopoietic Cell Transplant and Cell Therapy Programs from the 10 collaborating institutions. We also thank the GETH-TC group for its support, particularly Ángel Cedillo and Silvia Filaferro for their invaluable contribution in collecting the clinical data for this manuscript.

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Authors and Affiliations

  1. Clinical Hematology Department, Institut Català d’Oncologia-Hospitalet, IDIBELL, Barcelona, Spain

    M. Peña, D. F. Martinez, A. Paviglianiti & A. Mussetti

  2. Hematology Department, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau and José Carreras Leukaemia Research Institutes, Barcelona, Spain

    A. Paviglianiti

  3. Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. CIBERONC, Instituto Carlos III, Madrid, Spain

    A. Balaguer & J. Sanz

  4. Departament de Medicina, Universitat de Valencia, Valencia, Spain

    J. Sanz

  5. Hematology Department, Hospital Regional Universitario de Málaga, Málaga, Spain

    M. J. Pascual & B. Herruzo

  6. Hematology Department, Hospital Clínico Universitario de Valencia-INCLIVA, Valencia, Spain

    C. Solano & A. Benzaquén

  7. Hematopoietic Cell Transplantation Unit, Hospital Clínic de Barcelona, ICHMO, Barcelona, Spain

    M. Q. Salas & M. Rovira

  8. Hematology Department, Complexo Hospitalario de Vigo - Hospital Álvaro Cunqueiro, Vigo, Spain

    A. Nieto

  9. Hematology Department, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain

    I. Español

  10. Hematology Department, Institut Català d’Oncologia-Badalona, Hospital Germans Trias i Pujol, Barcelona, Spain

    M. Huguet

  11. Hematology Department, Hospital Universitario Son Espases, IdISBa, Palma De Mallorca, Spain

    L. Bento

  12. Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    A. J. Saéz

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Contributions

Contribution: MP and AM designed the study. DFM and AP performed the statistical analysis. MP, DFM and AP created the figures and wrote the manuscript. AM, AB, JS, MJP, BH, CS, AB, MQS, MR, AN, IE, MH, LB and AJS contributed to patient care and data collection, provided valuable input during the study, and reviewed the manuscript.

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Correspondence to M. Peña.

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Peña, M., Martinez, D.F., Paviglianiti, A. et al. Thiotepa, busulfan and fludarabine conditioning regimen for adult patients with lymphoid malignancies undergoing allogeneic stem cell transplantation: a study on behalf of GETH-TC. Bone Marrow Transplant 60, 795–803 (2025). https://doi.org/10.1038/s41409-025-02559-5

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