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Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years.

Human NK cells comprise two main subsets, CD56bright and CD56dim cells, which differ in function, phenotype, and tissue localization. To further dissect the differentiation from CD56bright to CD56dim cells, we performed ex vivo and in vitro experiments demonstrating that the CD56brightCD16+ cells are an intermediate stage of NK cell maturation. We observed that the maximal frequency of the CD56brightCD16+ subset among NK cells, following unrelated cord blood transplantation, occurs later than this of the CD56brightCD16- subset. We next performed an extensive phenotypic and functional analysis of CD56brightCD16+ cells in healthy donors, which displayed a phenotypic intermediary profile between CD56brightCD16- and CD56dimCD16+ NK cells. We also demonstrated that CD56brightCD16+ NK cells were fully able to kill target cells, both by Ab-dependent cell cytotoxicity (ADCC) and direct lysis, as compared with CD56brightCD16- cells. Importantly, in vitro differentiation experiments revealed that autologous T cells specifically encourage the differentiation from CD56brightCD16- to CD56brightCD16+ cells. Finally, further investigations performed in elderly patients clearly showed that both CD56brightCD16+ and CD56dimCD16+ mature subsets were substantially increased in older individuals, whereas the CD56brightCD16- precursor subset was decreased. Altogether, these data provide evidence that the CD56brightCD16+ NK cell subset is a functional intermediate between the CD56bright and CD56dim cells and is generated in the presence of autologous T CD3+ cells. [ABSTRACT FROM AUTHOR]