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

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