Impact of High Donor-Derived CD4⁺ CCR7⁺ T Cell Count on Incidence of Grade II-IV Acute Graft-Versus-Host Disease Following Haploidentical Hematopoietic Cell Transplantation

Introduction

Historically the administration of post-transplant high-dose Cyclophosphamide (PTCy) has led to haplo-HCT re-innovation.

Although PTCy has a positive impact towards reducing severe acute graft-versus-host disease (aGVHD), this drug has serious adverse side effects and makes haploidentical-HCT more difficult in some patients-particularly in older patients and/or those presenting other comorbidities.

Considering our previous published experience in the effect of graft lymphocyte composition, this work aims to explore the impact of infused T cell subsets on Overall Survival (OS), Event Free Survival (EFS) and acute GVHD in a retrospective cohort receiving allogeneic haplo-HCT.

Methods

This study retrospectively analyzed 29 adult patients who underwent first allogeneic haplo-HCT for hematologic malignancies at Lille University Hospital (CHRU Lille, France).

Graft samples were analyzed by flow cytometry, and CD4 and CD8 T cell subsets were defined as follows: T_N=naïve T cells; , T_CM=central memory T cells; T_EM=effector memory T cells; T_TD =terminally differentiated T cells.

Results

The median follow-up of patients was 11 months (0.4-44.3). The cohort median recipient age was 59 years old. Cumulative incidences of grade 2 to 4 aGVHD were 31%. The rate of grade 3 to 4 severe GVHD was 17%. Eleven patients died with 14% of deaths due to non-relapse mortality.

We found a correlation between high percentage of donor-derived CD4⁺ CCR7⁺ T cells (>69.2% for CD4⁺ T cells-the median value in our study) and aGVHD (p=0.028) without any impact on OS and EFS (Table 1).

In multivariate analysis, only high proportions of donor CD4⁺ CCR7⁺ T cells correlated significantly with aGVHD (HR=0.203, 95% CI [0,042-0,980], p=0,047) without any impact on OS and EFS (Figure 1).

Conclusion

Naïve and central memory T cells expressing CCR7 exhibit higher alloreactivity potential than CCR7^- T cells. In this study, even with PTCy administration, we observed that a high percentage of donor-derived CD4⁺ CCR7⁺ T cells can be considered as a predictive indicator of grade II-IV aGVHD post Haplo-HCT. Thus, selective depletion of CD4⁺ CCR7⁺ T cells might be enough to prevent aGVHD in haplo-HCT, enabling the use of low doses of PTCy in order to reduce post haplo-HCT complications.

View largeDownload slide

View largeDownload slide

Close modal