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Graft engineering procedures for hematopoietic SCT (HSCT) may improve the chance of success in matched unrelated donor (MUD) and haploidentical donor transplantations. Successful donor immune reconstitution is important to mediate GVL effects in reduced-intensity conditioning (RIC) HSCT. We prospectively investigated early immune reconstitution and clinical outcome in 30 CD3/CD19-depleted MUD (n=15) or HP (n=15) HSCTs for high-risk childhood leukemia using a fludarabine-based RIC without serotherapy. The graft consisted of a mean of 10.5 × 106/kg CD34+, 77 × 103/kg CD3+ and 39 × 106/kg CD56+ cells. After transplantation, 86% of the patients engrafted. In all, 13% of patients had >grade 3 acute GVHD. Natural killer (NK) cell, DC and T-cell recovery achieved normal values within the first 60 days after transplantation. DC recovery was dominated by the DC2− subset. NK-cell phenotype was altered and cytotoxicity was lower compared with their donors. EFS was 50±9% (73±11% for those in CR1 and 26±11% for those with advanced disease). Faster DC2− recovery was associated with better outcome, especially in the MUD setting. In summary, CD3/CD19-depleted HSCT with fludarabine-based RIC without serotherapy resulted in favorable patient survival, and rapid NK, DC and T-cell recovery. [ABSTRACT FROM AUTHOR]

The article discusses the essential characteristics of natural killer (NK) cells which are known to have an important role in inherited defense against viruses, as well as against tumor cells. It suggests that the transplanted stem cells produce NK cell wave that contained alloreactive NK cells. It also notes that the study by Giebel and others provides useful information for better understanding of how NK cell reconstitute the repertoire of their receptors.