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Alemtuzumab-based conditioning regimen before hematopoietic stem cell transplantation in patients with short telomere syndromes: a retrospective study of the SFGM-TC

Bone Marrow Transplantation volume 59, pages 1428–1432 (2024)Cite this article

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Abstract

While HSCT is the only curative option for patients with short telomere syndromes (STSs) and severe bone marrow failure (BMF) or myeloid malignancies (MM), their increase sensitivity to conditioning regimen strongly affect outcomes. To minimize HSCT related mortality, alemtuzumab-based conditioning regimens have been proposed, but the number of patients transplanted with those regimens reported in the literature remains very low. We retrospectively analyzed outcome of adults and adolescents with STSs transplanted after an alemtuzumab, fludarabine and cyclophosphamide based regimen registered by the SFGM-TC. Seven patients were transplanted for a BMF and 5 for a MM (median age 34 years, (IQR [22–45])). The 2-year GRFS for patients with MM was 20% (95% CI [3;100]), and 57% (95% CI [30;100]) in others. In univariate (hazard ratio, HR = 6, 95% CI [1;31]) and multivariate analysis (HR = 26, 95% CI [2;414]) stem cell source was a predictive factor for GRFS. Three of the 5 patients with pre-transplant MM relapsed and 2 of them died at last follow up. The 2-year OS was 66% (95% CI [43;99]) in the whole cohort with a median follow up of 32 months (IQR [13–56]). In conclusion, Alemtuzumab-based conditioning regimen with bone marrow is an option for patients with STSs and BMF, but others modalities have to be explored for patients with MM.

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Fig. 1: Outcomes.
Fig. 2: GRFS according to pre-graft hematological malignancies.

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Data availability

Anonymized patient source data are not available; all relevant analyzed data are included in the manuscript and supplementary materials.

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Acknowledgements

The authors would like to thank Philip Robinson (Direction de la Recherche en Santé, Hospices Civils de Lyon, Hôpital Lyon Sud, France) for help in manuscript preparation and Nicole Raus for help in data collection.

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Authors and Affiliations

  1. Hospices Civils de Lyon, Hôpital Lyon Sud, Service d’Hématologie Adulte, Lyon, France

    Rim Hussein-Agha

  2. Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Laboratoire de Génétique, Paris, France

    Caroline Kannengiesser

  3. Université Paris Cité, Paris, France

    Caroline Kannengiesser, Elodie Lainey, Gerard Socié & Regis Peffault de Latour

  4. Assistance Publique des Hôpitaux de Paris, Hôpital Robert-Debré, Laboratoire d’Hématologie, Paris, France

    Elodie Lainey

  5. Assistance Publique des Hôpitaux de Paris, Service d’Hématologie Adulte, Hôpital Necker-Enfants Malades, Paris, France

    Ambroise Marcais

  6. Centre Hospitalier Universitaire de Lille, Service d’Hématologie Transfusion, Lille, France

    Micha Srour

  7. Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Service d’Hématologie-Oncologie Pédiatrique, Marseille, France

    Arthur Sterin

  8. Centre Hospitalier Universitaire de Rouen, Service d’Hématologie-Oncologie Pédiatrique, Rouen, France

    Nimrod Buchbinder

  9. Service de Pneumologie A Hôpital Bichat, APHP, Paris, France

    Raphael Borie

  10. Université Paris Cité, Inserm, PHERE, Université Paris Cité, 75018, Paris, France

    Raphael Borie

  11. Assistance Publique des Hôpitaux de Paris, Hôpital Beaujon, Service d’Hépatologie, Paris, France

    Aurelie Plessier

  12. Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Service d’Hématologie Greffe de Moelle & Centre de référence national des aplasies médullaires acquises et constitutionnelles, Paris, France

    Gerard Socié, Regis Peffault de Latour & Flore Sicre de Fontbrune

Authors
  1. Rim Hussein-Agha
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  2. Caroline Kannengiesser
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  3. Elodie Lainey
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  4. Ambroise Marcais
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  6. Arthur Sterin
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  7. Nimrod Buchbinder
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  9. Aurelie Plessier
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  10. Gerard Socié
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  11. Regis Peffault de Latour
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  12. Flore Sicre de Fontbrune
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Contributions

RHA: substantial contribution to drafting the manuscript, analysis and interpretation of the data, final approval of the manuscript, and agreement to be accountable for all aspects of the work. FSdF and RPdL: substantial contribution to the design of the work, research methodologies, interpretation of data, drafting the manuscript, final approval of the version to be published, and agreement to be accountable for all aspects of the work. CK, EL, AM, IYA, AS, NB and NR: substantial contribution to data acquisition, revising the manuscript critically for important intellectual content, final approval of the manuscript, and agreement to be accountable for all aspects of the work. GS: final approval of the manuscript, and agreement to be accountable for all aspects of the work.

Corresponding author

Correspondence to Flore Sicre de Fontbrune.

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The authors declare no competing interests.

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This research including human data is in accordance with the declaration of Helsinski. The study has been validated by the ethic committee of the SFGM-TC and registered in the Health Data Hub with number I06152104202020. An inform consent was obtain from all the subjects or their legal representatives.

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Hussein-Agha, R., Kannengiesser, C., Lainey, E. et al. Alemtuzumab-based conditioning regimen before hematopoietic stem cell transplantation in patients with short telomere syndromes: a retrospective study of the SFGM-TC. Bone Marrow Transplant 59, 1428–1432 (2024). https://doi.org/10.1038/s41409-024-02381-5

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