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Early lymphocyte reconstitution and viral infections in adolescents and adults transplanted for sickle cell disease

Bone Marrow Transplantation (2024)Cite this article

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Allogeneic hematopoietic stem cell transplantation is a curative therapy for sickle cell disease (SCD). Most reports concern myeloablative (MAC) matched related transplants (MRT) performed in children. Older age is associated with increased toxicity of transplants, resulting in new approaches with reduced intensity conditioning (RIC) regimens for adults. A non-myeloablative (NMA) conditioning regimen based on low-dose total body irradiation (TBI) and anti-T-cell serotherapy with alemtuzumab has shown a favorable toxicity profile in adults, without severe GVHD and with an acceptable incidence of graft failure [1]. Furthermore, a haplo-identical related transplant (HRT) can be considered as a suitable alternative for patients lacking a matched donor. For adults, this approach is based on a reduced intensity conditioning (RIC) regimen including anti-thymocyte globulin and GVHD prophylaxis with post-transplant cyclophosphamide [2, 3]. All these regimens include in vivo T-cell depletion by serotherapy which may impair post-transplant lymphocyte recovery and increase the risk of viral infections [1, 2, 4]. To date, lymphocyte reconstitution after transplantation for adolescents and adults with SCD has still been little investigated [1, 4,5,6]. Here, we assessed whether in-vivo donor T-cell depletion is not associated with a limiting rate of infections and delayed lymphocyte reconstitution.

Patients transplanted from January 2008 to November 2021 in Saint Louis and Robert Debré hospitals were eligible if they were older than 13 years old at transplantation, and if they were monitored by flow cytometry analysis for post-transplant lymphocyte recovery. Patients who experienced graft failure or patients with follow-up shorter than 12 months were excluded. Patients, donors, or their guardians provided written informed consent for data analysis and the study was approved by the local committee of the “Centre Hospitalier Intercommunal de Creteil”: approval number 2022-01-07.

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Data availability

Original data are available by request to the corresponding author.

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Authors and Affiliations

  1. Hematology Adolescent and Young Adult Unit, St-Louis University Hospital, AP-HP, Paris, France

    Loïc Vasseur, Florian Chevillon, Aude-Marie Fourmont, Nicolas Boissel & Nathalie Dhédin

  2. Immunology laboratory, St-Louis University Hospital, AP-HP, Paris, France

    Alexis Cuffel, Florence Morin, Clara Ibanez & Sophie Caillat-Zucman

  3. Referral Center for Sickle Cell Disease, Pediatrics, CHIC Hospital, Créteil, France

    Corinne Pondarré

  4. Inserm U955, Paris XII University, Créteil, France

    Corinne Pondarré

  5. Pediatric immuno-hematology, Robert Debré University Hospital, AP-HP, Paris, France

    Jean-Hugues Dalle & Karima Yakouben

  6. French Sickle Cell Referral Centre, Department of Internal Medicine, Georges Pompidou European Hospital, Université de Paris Cité, AP-HP, Paris, France

    Edouard Flamarion & Jean-Benoit Arlet

  7. Immunology laboratory, Robert Debré University Hospital, AP-HP, Paris, France

    Valérie Guérin-El Khourouj

  8. Transplant department, St-Louis University Hospital, AP-HP, Paris, France

    Régis Peffault de Latour

  9. URP-3518, Saint-Louis Research Institute, Université de Paris Cité, Paris, France

    Nicolas Boissel

  10. Hematology laboratory, St-Louis University Hospital, AP-HP, Paris, France

    Hélène Moins-Teisserenc

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  1. Loïc Vasseur
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Contributions

A.C., V.G-E., F.M., C.I., H.M-T., and S.C-Z. performed the flow-cytometry and analyzed the data; L.V. and N.D. analyzed the data and drafted the manuscript; CP., J-H.D, S.C-Z., and N.D. supervised the study; C.P., J-H.D., F.C., A-M.F., E.F., K.Y., R.P-d-L., N.B., and J-B.A. provided clinical data. All authors revised the manuscript and approved its final version.

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Correspondence to Nathalie Dhédin.

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Vasseur, L., Cuffel, A., Pondarré, C. et al. Early lymphocyte reconstitution and viral infections in adolescents and adults transplanted for sickle cell disease. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02224-3

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