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Utility of the 2024 best practice recommendations from the EBMT Cellular Therapy and Immunobiology Working Party for use of donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 60, pages 247–249 (2025) Cite this article

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Donor lymphocyte infusions (DLI) are a well-established and widely employed strategy to increase the graft-versus-tumor (GvT) effect of allogeneic hematopoietic stem cell transplantation (HSCT) and/or to sustain donor engraftment in case of mixed chimerism [1, 2]. Unfortunately, the use of DLI is associated with an important non-relapse mortality (NRM) mainly secondary to the induction of graft-versus-host disease (GvHD) [3]. To optimize the risk/benefit ratio of such adoptive immunotherapy, Simona Pagliuca and colleagues recently reported on behalf of the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Bone Marrow Transplantation (EBMT) society, a series of consensus-based recommendations for the administration of unmanipulated DLI after allogeneic HSCT [4]. In the published recommendations, the EBMT CTIWP proposes the use of T cell doses adapted to the DLI indication (prophylactic, pre-emptive and therapeutic), the donor type (matched related donor, MRD; matched unrelated donor, MUD; and mismatched unrelated donor, MMUD, or haploidentical donor) and the time of infusion (3 months or 6 months or later after allogeneic HSCT) [4]. For prophylactic DLI, EBMT experts recommend a first DLI dose administered between 3- and 6-months post transplantation of 1 × 10e5 CD3/kg independently of donor type. If administered later than 6 months after transplantation, a first dose of 1 × 10e6/kg was recommended for DLI from matched related donors (MRD) as well as matched unrelated donors (MUD) while the dose was reduced to 5 × 10e5/kg for originating from mismatched unrelated donors/haploidentical donors (MMUD/haplo). For pre-emptive DLI administered between 3- and 6-months post transplantation, EBMT’s experts recommended a first DLI dose of 1–5 × 10e5/kg if in case of MRD and of 1 × 10e5 CD3/kg in case of MUD or MMUD/haplo. If the pre-emptive DLI is given later than 6 months after transplantation, the first recommended DLI dose is 1–3 × 10e6 CD3/kg if MRD, 1 × 10e6 /kg if MUD and 5 × 10e5/kg if MMUD/haplo. Finally, in case of relapse, therapeutic DLI at a starting dose of 1 × 10e7 CD3/kg for MRD or MUD, and of 1 × 10e6/kg for MMUD/Haplo was recommended.

Given the absence of robust prospective data, the EBMT 2024 recommendations were mostly based on expert consensus and their external validation is therefore needed to support their widespread use in clinical practice. To evaluate the utility of these recommendations on real-world data, we retrospectively analyzed a cohort of 162 patients receiving DLI after allogeneic HSCT at our center between January 2010 and December 2023. Patients’ characteristics are summarized in Table 1. Median age at allogeneic HSCT was 51 years (range 15–74). Transplantation indication was acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in 57% of patients, acute lymphoblastic leukemia (ALL) in 12%, lymphoma or chronic lymphocytic leukemia (CLL) in 13%, chronic myeloid leukemia (CML) in 7%, and other hematological malignancies in 6%. First dose of DLI was infused at a median time of 214 days (range 60–3753 days) after allogeneic HSCT. No patient received immunosuppressive drugs at time of DLI. Thirty-eight percent of patients had a history of GvHD (acute GvHD, n = 61 and/or chronic GvHD, n = 11) resolved at time of DLI. Median number of DLI was 2 (range 1–7).

Table 1 Patients’ characteristics.
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Fig. 1: Utility of the EBMT 2024 recommendations on DLI use.
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References

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Authors and Affiliations

  1. Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland

    Anne-Claire Mamez, Amandine Pradier, Sarah Morin, Federica Giannotti, Chiara Bernardi, Stavroula Masouridi-Levrat, Yves Chalandon & Federico Simonetta

  2. Translational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Amandine Pradier, Sarah Morin, Chiara Bernardi, Yves Chalandon & Federico Simonetta

  3. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Amandine Pradier, Chiara Bernardi & Federico Simonetta

Authors
  1. Anne-Claire Mamez
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  2. Amandine Pradier
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  3. Sarah Morin
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  4. Federica Giannotti
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  7. Yves Chalandon
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  8. Federico Simonetta
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Contributions

ACM and FS conceived and designed the study; ACM, AP, SM, FG, CB and SML collected the data; ACM, AP and FS analyzed and interpreted the data; SM, FG, CB, SML and YC contributed to the interpretation of the data; ACM and FS wrote the manuscript; FS supervised the research; all authors read, edited, and approved the submitted version of the manuscript.

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Correspondence to Anne-Claire Mamez or Federico Simonetta.

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Competing interests

ACM: nothing to disclose. AP: nothing to disclose. SM: nothing to disclose. FG: nothing to disclose. CB: research funding from BMS/Celgene. SML: nothing to disclose. YC: consulting fees for advisory board from MSD, Novartis, Incyte, BMS, Pfizer, Abbvie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca, Servier, Pierre Fabre, Medac; Travel support from MSD, Roche, Gilead, Amgen, Incyte, Abbvie, Janssen, Astra-Zeneca, Jazz, Sanofi, Pierre Fabre all via the institution. 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.

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Mamez, AC., Pradier, A., Morin, S. et al. Utility of the 2024 best practice recommendations from the EBMT Cellular Therapy and Immunobiology Working Party for use of donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 60, 247–249 (2025). https://doi.org/10.1038/s41409-024-02458-1

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