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Graft-Versus-Host Disease

Escalated lymphodepletion followed by donor lymphocyte infusion can induce a graft-versus-host response without overwhelming toxicity

Bone Marrow Transplantation volume 47, pages 1112–1117 (2012)Cite this article

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Abstract

Treatment of relapse of hematological malignancies following allogeneic hematopoietic SCT (allo-HSCT) remains very challenging and relies usually on the readministration of chemotherapy combined with donor lymphocyte infusion (DLI). To enhance DLI effectiveness, lymphodepletion (LD) with fludarabine (Flu) and/or CY before the injection of lymphocytes is an attractive modality to modify the immune environment, leading possibly to suppression of regulatory T cells (Treg) and exposing the patient to cytokine activation. However, LD before DLI may lead to induction of deleterious GVHD. To avoid inducing overwhelming toxicity, we proceeded by escalating doses of both LD and DLI. Eighteen patients with various non-CML hematological malignancies who relapsed following allo-HSCT were treated with chemotherapy and LD-DLI or LD-DLI upfront. T-cell subpopulation and DC levels as well as cytokine plasma levels (IL-7, IL-15) were measured before and following LD-DLI. Cumulative incidence of acute grade II–IV GVHD was 29.4% similar to that reported in patients receiving DLI without LD. In addition, Flu alone with low dose of DLI was not associated with severe GHVD. CY/Flu at the respective doses of 600 mg/m2 on day 1 and Flu 25 mg/m2/day on days 1–3 did not result in a marked decrease of Treg cells, nor in endogenous IL-7 and IL-15 production. However, a peripheral expansion of DCs was observed. These findings suggest that the escalated dose procedure appears safe and prevent overwhelming toxicity. A dose-limiting toxicity has not yet been reached.

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Acknowledgements

We thank V Dehame for his technical assistance with the samples, and the nursing staff for providing excellent patient care. We also thank the Ligue contre le cancer, the Région Pays de Loire, the Association pour la Recherche sur le Cancer (ARC), the Fondation de France, the Fondation contre la Leucémie, the Agence de Biomédecine, the Association Cent pour Sang la Vie, and the Association Laurette Fugain for their generous and continuous support for the clinical and basic research work.

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Authors and Affiliations

  1. Centre Hospitalier et Universitaire (CHU) de Nantes, Hématologie Clinique, Nantes, France

    T Guillaume, P Chevallier, J Delaunay, S Ayari, A Clavert, F Rialland, S Le Gouill, N Blin, T Gastinne, B Mahé, V Dubruille, P Moreau & M Mohty

  2. INSERM CRCNA, UMR 892, Nantes, France

    T Guillaume, P Chevallier, S Le Gouill, P Moreau & M Mohty

  3. Centre d’Investigation Clinique en Cancérologie (CI2C), Nantes, France

    T Guillaume, P Chevallier, J Delaunay, S Ayari, A Clavert, F Rialland, S Le Gouill, N Blin, T Gastinne, B Mahé, V Dubruille, P Moreau & M Mohty

  4. INSERM UMR645, Besançon, France

    B Gaugler

  5. EFS Bourgogne Franche-Comté, Besançon, France

    B Gaugler

  6. Université de Franche-Comté, IFR133, Besançon, France

    B Gaugler

  7. Centre d’Investigation clinique en Biothérapie CBT506, Plateforme de Biomonitoring, Besançon, France

    B Gaugler

  8. Université de Nantes, Nantes, France

    S Le Gouill, P Moreau & M Mohty

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  1. T Guillaume
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Correspondence to T Guillaume.

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Guillaume, T., Gaugler, B., Chevallier, P. et al. Escalated lymphodepletion followed by donor lymphocyte infusion can induce a graft-versus-host response without overwhelming toxicity. Bone Marrow Transplant 47, 1112–1117 (2012). https://doi.org/10.1038/bmt.2011.231

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