Adequate CD4+ T-cell reconstitution enhances survival probability after acute graft-versus-host-disease

Abstract

Background & Aim Background Acute Graft-versus-Host-Disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic (stem) cell transplantation (HCT). Studies evaluating the relation between immune reconstitution (IR) and aGvHD are largely lacking. We previously showed that successful CD4+ IR strongly predicts event-free survival chances. Therefore, we studied how CD4+ IR post-HCT influences survival chances in patients suffering from aGvHD. Methods, Results & Conclusion Methods Pediatric patients receiving their first allogeneic HCT between 2004 and 2018 were included. Blood samples and outcome data were collected and registered prospectively. The main outcomes of interest were 5-year overall survival (OS) and non-relapse mortality (NRM) probabilities, stratified for aGvHD (grade II-IV) and for the presence or absence of adequate CD4+ IR (twice >50*10 6 CD4+CD3+ cells/L) prior to aGvHD onset. For this, we applied a time-to-event multivariate Log-rank test with HCT-source; cord blood transplantation, and bone marrow or peripheral blood transplantation, as covariates. Results 276 pediatric patients with a median age of 7.06 years (range 0.16-22.74), were included; 73 (26.4%) had moderate-severe aGvHD (grade II-IV) and 29 (10.5%) had severe aGvHD (grade III-IV). Adequate early CD4+ IR before diagnosis of aGvHD grade II-IV was associated with higher 5-year OS probability (77% versus 48%, p Interpretation Adequate CD4+ IR prior to aGvHD onset protects against increased mortality risk after aGvHD in HCT. These findings provide insight in the importance of adequate IR in HCT patients in surviving severe aGvHD. Patients with inadequate CD4+ T-cells prior to aGvHD onset might may have insufficient development of regulatory processes and are more at risk for viral infections. As such, these patients may benefit from personalized (anti-viral / immune suppressive) treatment to improve survival chances.