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Clofarabine and total body irradiation (TBI) as conditioning regimen for allogeneic stem cell transplantation in high-risk acute leukemia patients: a two-center retrospective cohort study

Bone Marrow Transplantation volume 58, pages 667–672 (2023)Cite this article

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Abstract

Clofarabine (Clo) is an immunosuppressive purine analog that may have better anti-leukemic activity than fludarabine (Flu). The addition of total body irradiation (TBI) to conditioning regimens has been widely investigated. However, the use of single agent Clo in combination with intermediate doses of TBI ranging from 4 to 8 Gy has not been studied yet. This study is a double center, observational, retrospective study of patients with high-risk hematological malignancies diagnosed from 2012 to 2021, treated at the American University of Beirut Medical Center in Beirut (AUBMC), Lebanon, and Saint-Antoine Hospital (SAH) in Paris, France. It aims to identify the outcome of patients with high-risk hematological malignancies who underwent allogeneic stem cell transplant (allo-SCT) and received Clo and TBI (4–8 Gy) before transplant. Data regarding patient baseline characteristics, disease-related factors, and transplant outcomes including graft-versus-host disease (GVHD), Non-relapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), were collected. We identified 24 high-risk patients diagnosed with a hematological malignancy. The median age at transplant was 37 years (range 22–78). At the time of the transplant, only 15 patients (63%) were in complete remission (CR). All patients received Clo/TBI (4–8 Gy). After a median follow-up of 40 months, the cumulative incidences of grade II-III acute GVHD, grade IV acute GVHD, and chronic GVHD were 50%, 4%, and 8%, respectively. NRM at 100 days, and 1 year after transplant was 4% and 25%, respectively. 17% of the patients had a relapse or progression of the disease by the end of the study. The 2-year PFS and OS were 50% and 56%, respectively. The median PFS and OS were 66 and 68 months respectively. As a conclusion, Clo/TBI (4–8 Gy) as a conditioning regimen for allo-SCT in high-risk patients confers disease control with an acceptable toxicity profile.

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Data availability

The datasets obtained, organized, and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the nursing staff and all the physicians at our two centers for providing excellent patient care.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Jean El Cheikh, Ghassan Bidaoui, Ali Atoui, Khodr Terro, Layal Sharrouf, Nour Moukalled, Imane Abou Dalle & Ali Bazarbachi

  2. Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Jean El Cheikh, Ammar Zahreddine, Nour Moukalled, Imane Abou Dalle & Ali Bazarbachi

  3. Department of Hematology, Saint Antoine Hospital, INSERM UMR 938, Sorbonne University, Paris, France

    Mohamad Mohty & Remy Dulery

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  1. Jean El Cheikh
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Contributions

JLC, the corresponding and first author, came up with the idea given the gap in the literature. JLC also supervised the study wrote and reviewed the manuscript extensively. GB, the second author, synthesized the manuscript writing, contributed in data collection, and reviewed the paper extensively. AA, KT and LS contributed extensively in the data collection and cleaning. AZ contributed to patient and case database organization and management. NM, IAD, AB, MM, RD reviewed the manuscript and were in charge of patients and all authors reviewed its final version.

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Correspondence to Jean El Cheikh.

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The authors declare no competing interests.

Ethics approval

This study gained international review board approval and ethics committee approval in the AUMBC and SAH. All patients gave informed consent for the collection of their data in this database. Data were collected from chart reviews, and test results were cross-checked using various methods of verification, including matching of several sources of data, on-site verification, and computerized searches for discrepancy errors.

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El Cheikh, J., Bidaoui, G., Atoui, A. et al. Clofarabine and total body irradiation (TBI) as conditioning regimen for allogeneic stem cell transplantation in high-risk acute leukemia patients: a two-center retrospective cohort study. Bone Marrow Transplant 58, 667–672 (2023). https://doi.org/10.1038/s41409-023-01947-z

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