Dynamical System Modeling Of Immune Reconstitution Following Allogeneic Stem Cell Transplantation Identifies Patients At Risk For Adverse Outcomes

TL;DR

This study models immune reconstitution after stem cell transplantation as a dynamical system, identifying patterns linked to patient outcomes and potential for early risk intervention.

Contribution

It introduces a novel dynamical systems approach to analyze immune recovery, revealing distinct patterns associated with clinical outcomes in transplant patients.

Findings

Three lymphocyte recovery patterns identified with different clinical implications.

Pattern A linked to higher GVHD incidence; Pattern C associated with relapse and DLI.

Early immune reconstitution metrics predict patient risk for adverse outcomes.

Abstract

Systems that evolve over time and follow mathematical laws as they do so, are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using anti-thymocyte globulin (ATG) and 4.5 Gray total-body-irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft vs. host disease (GVHD) were not significantly different in two cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ (ddCD3) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated one of three sigmoid growth patterns; Pattern A (n=15), had rapid growth with high lymphocyte counts, pattern B (n=14), slower growth with intermediate recovery and pattern C, poor lymphocyte reconstitution (n=10). There was a significant association between lymphocyte recovery patterns and both the rate of change of ddCD3 at day 30 post-SCT and the clinical outcomes. GVHD was observed more frequently with pattern A; relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution following SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk.