Dynamic Immune Reconstitution and Clinical Outcomes of Three Different Protocols for Haploidentical Hematopoietic Stem Cell Transplantation

Abstract

The wider application of posttransplant cyclophosphamide (PTCY) and granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocols has revolutionized haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by decreasing graft-versus-host disease and facilitating engraftment. In this study, we compared the clinical outcomes and the immune reconstitution of propensity score-matched (1:1:1) patients receiving PTCY (n = 45), ATG (n = 45), or PTCY plus ATG (n = 45). Patients in the ATG group had significantly higher overall survival (OS) (p = 0.029) and leukemia-free survival (LFS) (p = 0.034). CD3⁺ (p < 0.01) and CD8+ T-cell counts (p = 0.02) were greater at 3 months after transplantation in the ATG group. After adjustment for relevant covariables, Cox models revealed a significant association between CD8⁺ T-cell reconstitution and OS in all patients (p = 0.008); CD8+ T-cell recovery and LFS showed a similar trend (p = 0.034). Sensitivity analysis revealed stable results. Restricted cubic spline curve analysis to visualize the relationship between immune reconstitution and outcomes revealed that the CD8⁺ T-cell count at 3 months post-HSCT strongly correlated with survival prognosis. These findings demonstrate that conditioning regimens profoundly impact immune reconstitution, which may contribute to differences in survival prognosis. Moreover, increasing the probability of CD8⁺ T-cell reconstitution after HSCT may become an important strategy for improving outcomes.

Keywords

Beijing protocol / conditioning regimen / haploidentical hematopoietic stem cell transplantation / immune reconstitution / posttransplant cyclophosphamide

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