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Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies

Bone Marrow Transplantation volume 55, pages 763–772 (2020)Cite this article

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Abstract

We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa–busulfan–fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa–etoposide–cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17–72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180–1595) days. The median days to neutrophil engraftment was 17 (range, 12–34). The cumulative incidences (CI) of acute graft-versus-host disease (GVHD) grade III to IV, severe chronic GVHD, nonrelapse mortality (NRM), and relapse were 16%, 16%, 26, and 26%, respectively. The 2-year overall survival (OS) and disease-free survival (DFS) were 53% and 47%, respectively. There were no significant differences between the patients in CR and R/R patients in terms of engraftment, GVHD, NRM, relapse, OS, or DFS. We conclude that thiotepa-based regimen with PT-CY can be modified with PBSC and ATG, still providing low toxicity, protection against GVHD, and low relapse incidence. Particularly encouraging are the results with the modification to sequential regimen in R/R patients.

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Acknowledgements

We thank the nursing staff for providing excellent care for our patients.

Funding

This study was supported by the Association for Training, Education, and Research in Hematology, Immunology, and Transplantation. All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

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  1. These authors contributed equally: Florent Malard, Mohamad Mohty

Authors and Affiliations

  1. Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France

    Zinaida Peric, Razan Mohty, Juliana Bastos, Eolia Brissot, Giorgia Battipaglia, Ramdane Belhocine, Simona Sestili, Federica Giannotti, Anne Vekhoff, Tounes Ledraa, Ollivier Legrand, Simona Lapusan, Francoise Isnard, Myriam Labopin, Agnes Bonnin, Clemence Mediavilla, Marie-Thérèse Rubio, Annalisa Ruggeri, Rémy Duléry, Florent Malard & Mohamad Mohty

  2. UMRS 938, Inserm, Paris, France

    Eolia Brissot, Giorgia Battipaglia, Ollivier Legrand, Myriam Labopin, Rémy Duléry, Florent Malard & Mohamad Mohty

  3. Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France

    Eolia Brissot, Giorgia Battipaglia, Ollivier Legrand, Myriam Labopin, Rémy Duléry, Florent Malard & Mohamad Mohty

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Contributions

ZP collected, assembled, and analyzed data, performed statistical analysis, and wrote the first version of the manuscript. MM designed the study, supervised research, analyzed data, and helped writing the manuscript. RD and RM collected and assembled data. All other co-authors collected, assembled, and analyzed data; recruited patients; and helped write the manuscript. ML helped analyze data and commented on the manuscript. All authors approved submission of the manuscript for publication purposes.

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Correspondence to Mohamad Mohty.

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Conflict of interest

MM, RD, FM, and MTR have received honoraria for lectures from Keocyt, whose drug was included in this study. MM received honoraria for lectures from Sanofi, whose drug was included in this study. The other authors declare that they have no conflict of interest.

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Peric, Z., Mohty, R., Bastos, J. et al. Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies. Bone Marrow Transplant 55, 763–772 (2020). https://doi.org/10.1038/s41409-019-0726-7

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