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Pre-emptive rituximab treatment for Epstein–Barr virus reactivation after allogeneic hematopoietic stem cell transplantation is a worthwhile strategy in high-risk recipients: a comparative study for immune recovery and clinical outcomes

Bone Marrow Transplantation volume 55, pages 586–594 (2020)Cite this article

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Abstract

This retrospective study evaluated the impact of a pre-emptive rituximab (RTX) strategy for Epstein–Barr virus (EBV) reactivation on immune recovery and outcomes of 219 high-risk recipients undergoing allogeneic stem cell transplantation (allo-SCT) for hematological malignancies or bone marrow failure. One-hundred and seven patients received pre-emptive RTX for EBV reactivation (RTX group) and 112 did not (control group). The median onset time of EBV reactivation was 49 days (range, 14–561), including five patients who developed post-transplant lymphoproliferative disorder (EBV-PTLD). RTX and control groups were pair-matched to assess the impact of RTX on all endpoints. In RTX patients, CD19 + B cells were significantly decreased until 1-year post-transplant, so were immunoglobulin levels. Twenty-one patients (17%) developed RTX-related neutropenia. There was, in the RTX group, a trend towards a lower cumulative incidence of chronic GvHD (P = 0.059). Overall survival, progression-free survival, non-relapse mortality, relapse incidence, and incidence of overall infections at 2 years following allo-SCT were comparable in the two groups. We conclude that pre-emptive RTX, despite inducing a delayed B-cell reconstitution and a high risk of RTX-related neutropenia, may be considered as a worthwhile treatment, given the absence of negative impact on post allo-SCT outcomes and a low incidence of EBV-PTLD.

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Acknowledgements

We acknowledge the Association for Training, Education and Research in Hematology, Immunology, and Transplantation for the generous and continuous support to the research work. This work was supported by a grant from IRGHET (International Research Group on HEmatopoietic cells Transplantation). We also thank the clinical teams who provided care for the study patients, the members of the tumor bank at Saint-Antoine Hospital and the members of the study team at the Center de Recherche Saint-Antoine for their dedication to this study.

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Authors and Affiliations

  1. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), 75012, Paris, France

    Nicolas Stocker, Inès Boussen, Florent Malard, Giorgia Battipaglia, Béatrice Gaugler, Mohamad Mohty & Eolia Brissot

  2. AP-HP, Hôpital Saint-Antoine, Service d’Hématologie Clinique Et Thérapie Cellulaire, 75012, Paris, France

    Myriam Labopin, Agnès Bonnin, Florent Malard, Giorgia Battipaglia, Rémy Duléry, Federica Giannotti, Annalisa Ruggeri, Béatrice Gaugler, Mohamad Mohty & Eolia Brissot

  3. Acute Leukemia Working Party, Paris Study Office, European Society for Blood and Marrow Transplantation, Paris, France

    Myriam Labopin, Mohamad Mohty & Eolia Brissot

  4. Sorbonne Université, Service Des Maladies Infectieuses, AP-HP, Hôpital Saint-Antoine, 75012, Paris, France

    Olivier Paccoud

  5. AP-HP, Service de Virologie, Hôpital Tenon, 75020, Paris, France

    Corinne Amiel

  6. Sorbonne Université, Service de Virologie, AP-HP, Hôpital Saint-Antoine, 75012, Paris, France

    Joël Gozlan

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  1. Nicolas Stocker
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Contributions

All authors listed on the manuscript have contributed substantially to this work: NS, ML, and EB designed the study, NS and AB collected the data, NS, FM, GB, RD, FG, AR, MM, and EB recruited the patients, ML performed the statistical analysis and NS, IB, and BG contributed the flow cytometry data. NS prepared the manuscript and figures for publication. All authors analyzed the data, reviewed the manuscript, and agreed to its submission for publication.

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Correspondence to Eolia Brissot.

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Stocker, N., Labopin, M., Boussen, I. et al. Pre-emptive rituximab treatment for Epstein–Barr virus reactivation after allogeneic hematopoietic stem cell transplantation is a worthwhile strategy in high-risk recipients: a comparative study for immune recovery and clinical outcomes. Bone Marrow Transplant 55, 586–594 (2020). https://doi.org/10.1038/s41409-019-0699-6

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