Baseline Thymopoietic Function and Post-Transplant Immune Recovery after Adult Cord Blood Transplantation

We previously published data from a group of 32 heavily treated adult cord blood transplant (CBT) recipients and found that their post-transplant immune recovery was characterized by a failure to recover early thymopoiesis and impairment of functional T cell recovery, compared to other recipients of autologous or allogeneic transplants (Komanduri et al., Blood, 2007).  We now report a more extensive study of adult CBT recipients in whom thymopoiesis was prospectively assessed by measuring T cell receptor excision circles (TRECs) in the peripheral blood.  Thymic function was assessed prior to CBT, and at varying intervals thereafter.  A total of 71 adult CBT recipients were assessed prior to CBT and also assessed at least once within the first 180 days after CBT.  Of these recipients, 44 of 71 had detectable thymopoiesis prior to the start of conditioning (62%), while baseline thymopoiesis was undetectable in others (38%).  In CBT recipients with detectable thymopoiesis at baseline, 32% had at least one sample demonstrating detectable thymopoiesis by six months post-transplant.  In contrast, only 4% of subjects with a negative baseline had any detectable thymopoiesis by six months.  These results suggest that the recovery of early thymopoiesis within the first six months of CBT in adults may be dependent on functional thymopoiesis at baseline.  Univariate landmark of a subset of these CBT recipients (n=41) stratified by the recovery of thymopoiesis at six months after CBT demonstrated that recovery of thymopoiesis was positively associated with overall survival (HR=0.2, 95% confidence interval 0.1-0.7, P=0.01), and also with decreased non-relapsed mortality (HR=0.2, 95% confidence interval 0.1-0.9, p=0.04).  Larger studies of baseline thymopoiesis prior to hematopoietic transplantation will be helpful to confirm these findings and ascertain how and why thymopoiesis is preserved in a subset of patients, and to determine more precisely the relationship of baseline function and post-CBT outcomes.