Joint models quantify associations between immune cell kinetics and allo-immunological events after allogeneic stem cell transplantation and subsequent donor lymphocyte infusion

Frontiers in Immunology

Immunology

Edouard F. Bonneville¹  Hein Putter¹  Liesbeth C. de Wreede¹  Daniëlle van Lammeren²  J. H. Frederik Falkenburg³  Peter A. von dem Borne³  Peter van Balen³  Eva A. S. Koster³  Erik W. A. Marijt³  Constantijn J. M. Halkes³  Jennifer M. L. Tjon³  Hendrik Veelken³  Tjeerd J. F. Snijders⁴ 

[1] Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands;Department of Hematology, HagaZiekenhuis, The Hague, Netherlands;Department of Hematology, Leiden University Medical Center, Leiden, Netherlands;Department of Hematology, Medisch Spectrum Twente, Enschede, Netherlands;

关键词: T-cell kinetics;    joint modelling;    allogeneic stem cell transplantation;    donor lymphocyte infusion;    graft-versus-host-disease;    T-cell depletion;    acute myeloid leukemia;    acute lymphoblastic leukemia;   

DOI  :  10.3389/fimmu.2023.1208814

 received in 2023-04-19, accepted in 2023-07-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

Alloreactive donor-derived T-cells play a pivotal role in alloimmune responses after allogeneic hematopoietic stem cell transplantation (alloSCT); both in the relapse-preventing Graft-versus-Leukemia (GvL) effect and the potentially lethal complication Graft-versus-Host-Disease (GvHD). The balance between GvL and GvHD can be shifted by removing T-cells via T-cell depletion (TCD) to reduce the risk of GvHD, and by introducing additional donor T-cells (donor lymphocyte infusions [DLI]) to boost the GvL effect. However, the association between T-cell kinetics and the occurrence of allo-immunological events has not been clearly demonstrated yet. Therefore, we investigated the complex associations between the T-cell kinetics and alloimmune responses in a cohort of 166 acute leukemia patients receiving alemtuzumab-based TCD alloSCT. Of these patients, 62 with an anticipated high risk of relapse were scheduled to receive a prophylactic DLI at 3 months after transplant. In this setting, we applied joint modelling which allowed us to better capture the complex interplay between DLI, T-cell kinetics, GvHD and relapse than traditional statistical methods. We demonstrate that DLI can induce detectable T-cell expansion, leading to an increase in total, CD4+ and CD8+ T-cell counts starting at 3 months after alloSCT. CD4+ T-cells showed the strongest association with the development of alloimmune responses: higher CD4 counts increased the risk of GvHD (hazard ratio 2.44, 95% confidence interval 1.45-4.12) and decreased the risk of relapse (hazard ratio 0.65, 95% confidence interval 0.45-0.92). Similar models showed that natural killer cells recovered rapidly after alloSCT and were associated with a lower risk of relapse (HR 0.62, 95%-CI 0.41-0.93). The results of this study advocate the use of joint models to further study immune cell kinetics in different settings.

【 授权许可】

Unknown   
Copyright © 2023 Koster, Bonneville, Borne, van Balen, Marijt, Tjon, Snijders, van Lammeren, Veelken, Putter, Falkenburg, Halkes and de Wreede