Abstract
Unmanipulated donor lymphocyte infusions (DLI) are crucial for enhancing the graft versus tumor (GVT) effect in post-transplant settings. Practices regarding DLI use vary widely among centers, encompassing differences in indications, prerequisites, and application methods. To explore current DLI policies, we developed a comprehensive survey that garnered responses from 165 EBMT centers across 43 countries. Notably, 97% of respondents reported using DLI in their practices. Indications for DLI included preemptive use for minimal residual disease (MRD) positivity in 86.9% of centers and mixed chimerism in 73.1%; therapeutic use for hematological relapse in 73.1%; and prophylactic use for high-risk disease in 43.8%. Active graft-versus-host disease (GVHD) and active infections were deemed absolute contraindications by 85.6% and 57.5% of centers, respectively. 35% of centers did not consider a prior history of acute (a)GVHD as an exclusion criterion. The majority (71.9%) requested immunosuppression withdrawal before DLI. Most centers (71.3%) collected DLI post-transplant, with 78.1% utilizing unstimulated apheresis. The cell doses applied at the first DLI varied significantly, depending on indication, timing, and donor type. This survey provides the largest overview of current DLI practices, highlighting the need for high-quality data to assess the risks and benefits of different approaches.
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Fig. 1
Fig. 2: Practices used to collect DLI.
Fig. 3
Data availability
The datasets generated during the current study are available from the Working Party chair upon reasonable request.
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Acknowledgements
The CTIWP of the EBMT extends its gratitude to clinicians and their teams for their dedication and efficiency in completing this survey in a timely manner. The authors thank the data management and statistical unit of the CTIWP of the EBMT, the clinical staff and all investigators involved in this research.
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Authors and Affiliations
Hematology Unit, Department of Oncology and Hematology, Santo Spirito Hospital, Pescara, Italy
Nicole Santoro
Department of Hematology and Oncology, Augsburg University Hospital and Medical Faculty Comprehensive Cancer Center Augsburg and Bavarian Cancer Research Center, Augsburg, Germany
Christoph Schmid
University Medical Centre, Utrecht, The Netherlands
Moniek de Witte
Radboud University Medical Center, Nijmegen, Netherlands
Mieke W. H. Roeven
Kings College Hospital London, London, UK
Victoria Potter
Southampton General Hospital, Southampton, UK
Deborah Richardson
University Hospital | Essen, Duesseldorf, Germany
Thomas Schroeder
Institute of Hematology and Blood Transfusion, Prague, Czechia
Veronika Válková
University College London Hospital, London, UK
Katherine Clesham
Centre Hospitalier Lyon Sud, Lyon, France
Sandrine Loron
University Hospital | Basel, Basel, Switzerland
Jakob Passweg
University Hospitals Bristol and Weston NHSFT, Bristol, UK
Caroline Besley
Department of Pediatrics, Jena University Hospital, Jena, Germany
Bernd Gruhn
EBMT Leiden Study Unit, Leiden, The Netherlands
Jorinde D. Hoogenboom
EBMT Statistical Unit, Leiden, The Netherlands
Jarl E. Mooyaart
Secretary of the Practice Harmonization and Guidelines Committee of EBMT; EBMT Medical Officer, Executive Office, Barcelona, Spain
Isabel Sanchez-Ortega
Department of Hematology, CNRS, Nancy University Hospital; UMR 7365, IMoPA, Lorraine University, Nancy, France
Simona Pagliuca
Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland
Federico Simonetta
Department of Medicine and Clinical Surgery, Federico II University of Naples, Naples, Italy
Giorgia Battipaglia
Division of Hematology, Nantes University Hospital; INSERM U1232 CNRS, CRCINA, Nantes, France
Thierry Guillaume
Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Mette D. Hazenberg
Sorbonne Université, Centre de Recherche Saint-Antoine INSERM UMRs938, Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France
Florent Malard
Department of Hematology and Center for Translational Immunology, UMC Utrecht, Utrecht, The Netherlands
Jürgen Kuball
San Raffaele Scientific Institute, Hematology and Bone Marrow Transplantation Unit, Milan, Italy
Annalisa Ruggeri
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Nicole Santoro
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Contributions
NS, CS, FM, JK, and AR designed the study and built up the survey. JH and ISO launched the survey to the centers and collected data. NS wrote the manuscript. JH and JM performed the descriptive analysis. CS, JK, AR, JHE, SP, FS, GB, TG, MDH, FM, and JH helped in data interpretation and revised the manuscript. VP, MdW, DB, MWHR, VV, HLW, TS, JP, CB, and BG were the principal investigators among the first ten participating centers reporting the highest number of DLIs to the Registry. All authors edited and approved the final version of the manuscript.
Corresponding author
Correspondence to Nicole Santoro.
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Competing interests
CS has received travel expenses or honoraria for participation in advisory boards, symposia or other scientific events by Novartis, Jazz Pharmaceutical, Neovii, Janssen, and Kite. FS institutional consulting fees from BMS/Celgene, Incyte, Kite/Gilead; speaker fees from Kite/Gilead, Incyte; travel support from Kite/Gilead, Novartis, AstraZeneca, Neovii, Janssen; research funding from Kite/Gilead, Novartis, BMS/Celgene. SP has received travel expenses or honoraria for participation in advisory boards, symposia, or other scientific events by Alexion, Novartis, Jazz Pharmaceutical, Therakos, OneLamda, Sobi as well as research funding by JANSSEN HORIZON program. JK has received grants from Novartis, Miltenyi Biotech, and Gadeta. JK was a Gadeta shareholder; patent licenses to Gadeta and Miltenyi Biotech. None of these disclosures construe a potential competitive interest with the research discussed in this article. All other co-authors declare no COI.
Ethics approval and consent to participate
The scientific board of the CTIWP of EBMT approved this study. All patients gave written informed consent for the use of their data. All methods were performed in accordance with the relevant guidelines and regulations.
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list of partecipating centers
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Santoro, N., Schmid, C., de Witte, M. et al. Current use of donor lymphocyte infusions after allogenic stem cell transplantation in Europe: a survey on behalf of the cellular therapy and immunobiology working party of the EBMT. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02555-9
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Received:30 October 2024
Revised:10 February 2025
Accepted:13 March 2025
Published:23 March 2025
DOI:https://doi.org/10.1038/s41409-025-02555-9
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