CD4+ Memory Stem-Cell T Lymphocyte Frequency Is a Marker of Alloreactivity and a Predictor of Long-Term Morbidity and Mortality After Hematopoietic Cell Transplantation

Abstract

Introduction: We aimed to describe T lymphocyte reconstitution during the first 100 days after allogeneic hematopoietic stem cell transplantation (HSCT) to identify differences associated with graft-versus-host disease (GvHD) manifestation.

Procedure: Eighty-three children who received transplants from unrelated donors were included in this single-institution study. Peripheral blood stem cells (PBSC) grafts and anti-T lymphocyte immunoglobulin (ATLG) were used.

Results: We observed greater proportions of CD8⁺ stem cell memory (SCMs) lymphocytes on day 28 in acute GvHD (aGvHD) patients and of CD4⁺ SCMs (CD3⁺TCRαβ⁺CD4⁺CD45RO-or CD45RA⁺CCR7⁺or CD62L⁺CD95⁺) on days 60 and 100 in chronic GvHD (cGvHD) patients. A greater proportion (≥5% CD4⁺ cells) of CD4⁺ SCMs on day 100 in patients with aGvHD was associated with a significantly greater cGvHD cumulative incidence (CI) (two-year value = 80.0% ± 0.9% vs. 27.1% ± 0.6%). Furthermore, a greater risk of non-relapse mortality (NRM) (two-year value = 16.1% ± 0.6% vs. 0%) and a lower risk of relapse (CI of relapse) (two-year value = 0% vs. 18.4% ± 0.3%) were observed in the group with a higher CD4⁺ SCM proportion on day 100, together with a lower probability of GvHD-free, immunosuppressive treatment-free, relapse-free two-year survival (GIRFS) (two-year value = 55.0% ± 11.1% vs.78.4% ± 7.3%).

Conclusion: CD4⁺ SCM frequency is a potential biomarker of allogeneic immune response intensity and cGvHD risk in the early posttransplantation period.

Keywords: Alloreactivity; CD4+ Memory Stem‐Cell T Lymphocytes; Graft‐Versus‐Host Disease; Hematopoietic Stem Cell Transplantation; Immune Reconstitution.