Double Umbilical Cord Blood Transplantation: Relevance of Persistent Mixed-Unit Chimerism

• Sustained hematopoiesis after double umbilical cord blood transplantation is from 1 donor unit, ie, single-unit dominance.
• Literature review revealed only 11 patients with stable mixed-unit chimerism.
• Clinical data for mixed-unit chimerism are scarce; enhanced graft-versus-leukemia effect is possible.
• Mechanisms for single-unit dominance, intrinsic graft features, and graft-versus-graft immune interactions.
• Understanding mechanisms of single-unit dominance may help improve patient outcomes

Double umbilical cord blood transplantation (UCBT) was developed as a strategy to circumvent the cell dose limitation of single UCBT with a concomitant potential benefit of lowering the rate of leukemia relapse. Sustained hematopoiesis after double UCBT usually is derived from a single donor unit, as only a few patients have been reported to display stable mixed-unit chimerism for varying periods of time. Explanations for the 1 unit dominance, predictors for identifying unit superiority, and persistence of long-term mixed-unit chimerism remain elusive. Review of published literature revealed only 11 of 280 patients (4%) with mixed-unit chimerism for at least 1 year after transplantation, with 3 patients receiving reduced-intensity conditioning regimens. Mixed-unit chimerism was more likely if both units were closely HLA matched to each other. Outcome data for patients with stable mixed-unit chimerism, for the most part, were scarcely reported. Analysis of the small sample size revealed a potential advantage of stable mixed-unit chimerism on enhancing the graft-versus-leukemia effect; however, definitive conclusions cannot be made on the effect of mixed-unit chimerism on the rates of graft-versus-host disease. Therefore, gathering outcome data prospectively in larger clinical series will help answer the question of whether stable mixed-unit chimerism is either beneficial and, therefore, should be strived for, detrimental and, thus, needs to be eliminated, or if it is of no clinical consequence.