# Dynamic immune reconstitution and clinical outcomes in different chimerism statuses of HLA-matched transplantation for severe aplastic anemia

## TL;DR

This study compares immune recovery and clinical outcomes in patients with severe aplastic anemia who have mixed or full donor chimerism after stem cell transplantation.

## Contribution

The study identifies immune dysregulation in mixed chimerism as a key factor in graft failure and highlights early immune monitoring as a potential strategy to improve outcomes.

## Key findings

- Mixed chimerism is linked to higher graft failure and delayed immune recovery compared to full donor chimerism.
- CD8+CD28+ T cell levels at 3 months predict better survival outcomes in mixed chimerism patients.
- Immune profiling reveals significant deficits in adaptive immunity in mixed chimerism cases.

## Abstract

This retrospective study examines the clinical outcomes and immune reconstitution dynamics in patients with severe aplastic anemia (SAA) exhibiting mixed chimerism (MC) compared with those with full donor chimerism (FDC) following HLA-matched hematopoietic stem cell transplantation (HSCT). Analysis of propensity score-matched cohorts (23 MC vs 69 FDC) revealed comparable 5-year overall survival (OS: 87.0% vs 92.8%, P = .433) but significantly inferior failure-free survival (FFS: 47.8% vs 87.0%, P < .001) in patients with MC due to a higher incidence of graft failure (52.2% vs 8.7%, P < .001). Longitudinal immune profiling revealed delayed recovery of myeloid and lymphoid lineages in patients with MC at 12 months post-HSCT, with pronounced deficits in adaptive immunity. Specifically, CD8+CD28+ T cell counts were consistently reduced at 1 month (median, 20 vs 41 cells/μL, P = .049), 3 months (median, 86 vs 153 cells/μL, P = .024), and 6 months (median, 109 vs 160 cells/μL, P = .001), and CD4+CD25+ T cells were diminished at 6 months (median, 11 vs 20 cells/μL, P = .006). Multivariate analysis revealed that elevated CD8+CD28+ T cell levels at 3 months (≥140 cells/μL) were an independent predictor of improved FFS (HR = 0.30, P = .035). These findings highlight MC-associated immune dysregulation, particularly impaired CD28-costimulated T cell and CD4+CD25+ T cell reconstitution, as a key mediator of graft instability. This study underscores the prognostic value of early immune monitoring and suggests therapeutic strategies that target T cell recovery to mitigate MC-related risk in patients with SAA.

Graphical Abstract