Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation

Abstract

Objective

This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT).

Methods

Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021.

Results

A higher dose of graft CD8⁺ T cells (≥ 0.85 × 10⁸ kg⁻¹) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; P = 0.002) and disease-free survival (DFS; HR, 1.751; P < 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; P = 0.038) and DFS (HR, 1.532; P = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8⁺ T-cell risk system based on graft CD8⁺ T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8⁺ T-cell dose was negatively correlated with donor age (P < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (P < 0.001).

Conclusion

A higher CD8⁺ T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.