Background: The impact of mixed chimerism (MC) in peripheral blood (PB) after myeloablative unmodified SCT is controversial. There are limited reports on the significance of MC after T-cell depleted (TCD) SCT. This study was undertaken to evaluate the impact of 3 month PB T cell MC (defined as < 80% donor) on outcomes at 2 yrs post-TCD SCT.
Methods: A retrospective review was conducted on adult patients who underwent TCD bone marrow (BM) or peripheral blood stem cell (PBSC) SCT from 1/2008-6/2011. PB chimerism (using short tandem repeat analysis on the T cell (TC) population) and disease status by BM evaluation were performed at 3, 6, 12, 18 and 24 months. No patient received a donor lymphocyte infusion (DLI) prior to 3 month landmark. Those who received DLI post-landmark were censored at time of DLI (N=15). Patient and SCT characteristics were compared using Wilcoxon's rank-sum test/Fisher's exact test. Disease free (DFS) and overall survival (OS) were estimated using Kaplan-Meier methods, and time-to-relapse and non-relapse mortality (NRM) were estimated using cumulative incidence functions. Cox regression was used to further investigate the association between chimerism and the risk of NRM adjusted for key covariates.
Results: Of 161 patients identified, 96 were disease free and had PB TC chimerism at 3 month Table 1 lists transplant characteristics and outcomes. PB TC MC was observed in 64 (66%) at 3 month There was no difference in chimerism based on disease, stem cell source, HLA-match, donor-recipient gender pairing, or conditioning regimen. Relapse and DFS were not different between the MC and full donor chimerism groups. However, NRM was significantly higher (P-value 0.001) and OS was significantly lower (P-value 0.01) in the full donor chimerism group at 2 years. Using Cox regression, the association between chimerism and NRM remained after adjusting for DLI, disease, conditioning regimen and donor-recipient sex (P value 0.03). Analysis of 6 month PB TC chimerism also showed patients with MC in the PB at 6 months had less NRM and improved OS than patients with full donor chimerism.
Conclusions: In this analysis of PB TC chimerism following TCD transplant, both NRM and OS were significantly better in patients with MC. These data suggest that DLI for the conversion of MC to full chimerism may be unnecessary.
Table 1. Characteristics and Outcomes