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Full donor chimerism without graft-versus-host disease: the key factor for maximum benefit of pre-emptive donor lymphocyte infusions (pDLI)

Bone Marrow Transplantation volume 55, pages 562–569 (2020)Cite this article

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Abstract

Compared to standard-conditioned regimens, reduced-intensity conditioning and T-cell depletion deliver lower transplant-related mortality and decreased graft-vs-host disease after allogeneic hematopoietic stem-cell transplantation. These advantages may however be mitigated by increased relapse rates and delays in achievement of full donor chimerism (FDC). Pre-emptive donor lymphocyte infusions (pDLI) facilitate the conversion of mixed (MDC) to FDC. However, there is a lack of published data on the risk/benefit analysis of this intervention. We performed a retrospective analysis of 119 patients who received 276 pDLI doses for falling CD3 chimerism, CD3 < 50% or mixed XX/XY karyotype. 71/119(60%) Patients achieved FDC, with only one reverting to MDC. Cumulative incidence (CI) of relapse at 5 years was significantly lower in the FDC group (16.0 vs 41.4%, p < 0.001). Those patients who achieved FDC had improved EFS (p < 0.001) and OS (p < 0.001). Interestingly, patients with FDC who developed DLI-induced graft-vs-host disease (GvHD) showed a similar outcome to those with MDC. The majority of patients who receive pDLI convert to FDC and retain that status. Achievement of FDC after pDLI impacts on survival, and those patients who achieve FDC without GvHD, experience maximum clinical benefit. Strategies to minimise DLI-induced GvHD should be considered to maximise the therapeutic potential of this intervention.

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Acknowledgements

The authors would like to thank the support from the Instituto de Salud Carlos III (Madrid, Spain) and to anonymous reviewers who gave valuable suggestion that has helped to improve the quality of the paper. We would also like to thank Diego Calavia for the statistics review of the paper.

Authors contributions

Conception and design: JF, VP, LB, AP, and GM. Provision of study materials or patients: JF, VP, FG, JC, LF, CS, GO, MK, HL, KR, DM. Collection and assembly of data: JF, VP, JC, LF, CS, GO, AAA, MK, and PK. Data analysis and interpretation: JF, VP, FG. Paper writing: All authors. Final approval of paper: All authors.

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Authors and Affiliations

  1. Servicio de Hematología, Hospital San Pedro, Logroño (La Rioja), Spain

    Jesus Feliu & Ricardo Garcia-Muñoz

  2. Haematology Department, King’s College Hospital, London, UK

    Victoria Potter, Lajos Floro, Michelle Kenyon, Pramila Krishnamurthy, Hugues de Lavallade, Kavita Raj, Donal McLornan, Antonio Pagliuca & Ghulam J. Mufti

  3. Divisione di Ematologia, Università Degli Studi Federico II, Napoli, Italy

    Francesco Grimaldi

  4. Haematology Department, St James’s University Hospital, Leeds, UK

    Jennifer Clay

  5. Haematology Department, Addenbrooke’s Hospital, Cambridge, UK

    Chandan Saha

  6. School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK

    Linda Barber

  7. Servei d’Hematologia i Hemoteràpia, Hospital Universitari de la Vall d’Hebron, Barcelona (Catalunya), Spain

    Guillermo Orti

  8. Medical Oncology Department, Zagazig University, Zagazig, Egypt

    Ahmad AbdelRaheem Alnagar

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  1. Jesus Feliu
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Correspondence to Jesus Feliu.

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Feliu, J., Potter, V., Grimaldi, F. et al. Full donor chimerism without graft-versus-host disease: the key factor for maximum benefit of pre-emptive donor lymphocyte infusions (pDLI). Bone Marrow Transplant 55, 562–569 (2020). https://doi.org/10.1038/s41409-019-0695-x

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