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Donor-derived CD4+/CCR7+ T-cell impact on acute GVHD incidence following haplo-HCT after reduced intensity conditioning and posttransplant cyclophosphamide

Bone Marrow Transplantation volume 54, pages 1686–1693 (2019)Cite this article

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Abstract

In previous studies, we and others observed in patients undergoing HLA-matched hematopoietic cell transplantation that high proportion of donor-derived CD4+/CCR7+ T cells were associated with an increased risk of acute GVHD without any interference in relapse incidence. We investigated the impact of donor-derived CD4+/CCR7+ T cells on patient outcome in haploidentical settings where posttransplant cyclophosphamide is used. We analyzed T-cell subsets in grafts of 29 adult patients who underwent first haploidentical transplant following reduced intensity conditioning. The median CD4+/CCR7+ subset proportion was 69.2% among donor CD4+ T cells. With a median follow-up of 28.1 months (range: 11.0–44.3), 16 patients (55%) developed acute GVHD; this includes 5 patients with grade 3 acute GVHD. Fifty-four percent of patients who received > 69.2% of CD4+/CCR7+ T cells and 12% of patients who received < 69.2% CD4+/CCR7+ T cells developed acute GVHD (p = 0.028). In multivariate analysis, a high proportion of CD4+/CCR7+ T cells was the only factor that impacted acute GVHD (HR = 4.925, 95% CI [1.020–23.775], p = 0,047) with no impact on overall survival. Our results confirm the impact of a high proportion of CD4+/CCR7+ T cells on acute GVHD incidence in patients undergoing haploidentical transplant despite the use of posttransplant cyclophosphamide.

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Acknowledgements

We thank all our patients and donors who participated in this study. We thank the Association Capucine for supporting our research. A special thanks to Rachel Tipton for checking the English of the manuscript.

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Author notes

  1. Tamim Alsuliman

    Present address: Service d’Hématologie, Hôpital Saint-Antoine, AP-HP, Université Pierre et Marie Curie (UPMC), 75012, Paris, France

  2. These first author contributed equally: Pauline Varlet and Tamim Alsuliman

Authors and Affiliations

  1. Institut d’Immunologie, CHRU, Lille, France

    Pauline Varlet, Jacques Trauet, Julie Demaret & Myriam Labalette

  2. LIRIC, Inserm U995, Université de Lille, 59000, Lille, France

    Pauline Varlet, Jacques Trauet, Julie Demaret, Myriam Labalette & Ibrahim Yakoub-Agha

  3. Unité d’Allogreffe, Maladies du sang, CHRU, 59000, Lille, France

    Tamim Alsuliman & Ibrahim Yakoub-Agha

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Designed and performed research: PV, TA, JT, and IYA. Analyzed and interpreted data: PV, TA, and IYA. Manuscript writing: all authors. Final approval of manuscript: all authors.

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Correspondence to Ibrahim Yakoub-Agha.

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Varlet, P., Alsuliman, T., Trauet, J. et al. Donor-derived CD4+/CCR7+ T-cell impact on acute GVHD incidence following haplo-HCT after reduced intensity conditioning and posttransplant cyclophosphamide. Bone Marrow Transplant 54, 1686–1693 (2019). https://doi.org/10.1038/s41409-019-0511-7

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