Donor T-cell and myeloid chimerism is higher after cord blood transplant than with other cell sources

Differences in multi-lineage and long-term donor chimerism after hematopoietic cell transplantation (HCT) from different cell sources are not well characterized, yet such information is crucial for understanding the distinct clinical utilities of each graft type. We analyzed donor chimerism outcomes in 472 pediatric allogeneic HCT recipients (2010-2020), including 115 unrelated cord blood (CB) grafts and 357 non-CB grafts (bone marrow or mobilized peripheral blood). Primary graft failure occurred more frequently in CB recipients (4.3% vs. 0.8%, P < 0.05), but among engrafted patients, initial mean donor chimerism at neutrophil recovery was comparable (∼99% in both groups, P = 0.5). At 6- and 12-months post-transplant, mean whole blood donor chimerism was significantly higher in the CB cohort (100% vs. 93.8% at 6 months; 99.2% vs. 91% at 12 months; P < 0.0001 for both). At 24 months' follow-up, mean donor chimerism remained nearly complete in CB recipients (99.2%) but declined in non-CB recipients (75%; P < 0.0001). Lineage-specific mean chimerism values at 6 months also favored the CB group, with higher donor myeloid (CD15⁺) chimerism (100% vs. 85.2%, P = 0.001) and donor T-cell (CD3⁺) chimerism (93% vs. 70%, P < 0.0001). Statistical analyses were performed using unpaired 2-tailed t-tests for comparing mean chimerism values and Kaplan-Meier methods were used to assess the cumulative probability of sustained complete donor chimerism. CB recipients had a significantly lower risk of developing mixed chimerism over time (hazard ratio, 0.5; 95% CI, 0.3-0.6, P = 0.002). In conclusion, CB transplantation is associated with more durable and complete multi-lineage donor chimerism, a finding that likely reflects the unique immunologic capacity of CB T cells to mediate rejection of residual host hematopoietic and immune cells. This robust donor dominance is particularly evident over time and across both myeloid and lymphoid compartments, suggesting a potent and sustained graft-versus-host hematopoietic effect. These findings underscore a continued and distinct role for CB as a stem cell source-not only in reducing post-transplant relapse in malignant disease through enhanced graft-versus-leukemia activity, but also in sustaining long-term donor-derived hematopoiesis and functional graft integrity in non-malignant disorders, including metabolic diseases in which stable enzyme delivery is critical.