The Epic Race to Immune Reconstitution

Abstract

Regardless of the hematopoietic stem cell (HSC) source, reconstitution of adaptive immunity is arguably the last great barrier to successful allogeneic hematopoietic cell transplantation. Early after transplantation, prolonged lymphocytopenia, and profound immune dysfunction result in infectious complications that are frequent and often life threatening [1]. In addition, delayed immune recovery may also increase the risk of relapse in patients treated for malignant disease [2,3]. The number of variables in the transplant recipient, such as patient age, graft source, HLA match, intensity of conditioning, and immune suppressive regimens make it difficult to identify the specific impact of a single variable. In addition, the absence of validated functional immune reconstitution assays hinders progress in the field. In this issue of BBMT, Jacobson and colleagues [4] tackle the clinical question of whether immune reconstitution in adult recipients of HLA mismatched umbilical cord blood (UCB) differs from that in adult recipients of HLAmatched unrelated peripheral blood (PB) transplantation. The data presented suggest that there may indeed be a significant delay in immune recovery after UCB transplantation. During the first 6-month period following transplantation, the absolute number of T cells and naive CD4 and CD4CD25T regulatory cell subsets were markedly reduced, whereas the number of B and natural killer cells was significantly higher in recipients of UCB compared to recipients of PB. Importantly, these differences were associated with higher rates of infectious complications in the UCB group (59% versus 8%, P .0001), with increases in bacterial, viral, and fungal pathogens during the same period. Despite these differences, risks of nonrelapse mortality and 2-year progression-free survival were similar between the 2 groups. As expected, based on prior reports, the inci-