Single or Double Cord Blood Unit for Transplant: What Have We Learned?

Abstract

The main obstacle to a more widespread use of UCBT in adults has been the short-term risk of graft failure and delayed hematopoietic recovery attributed to the low progenitor cells content of the graft. To overcome the cell dose limitation, the double cord blood transplantation (dUCBT) was originally conceived to enhance engraftment by augmenting graft cell dose with the combined transplantation of two partially HLA-matched UCB units. This transplant modality was pioneered by the Minnesota group and proved to be safe and feasible leading to long-term engraftment of only one unit (so-called predominant unit). Since then the activity of dUCBT in adults increased dramatically and soon surpassed the number of patients transplanted with a single unit (sUCBT), particularly for adults. Whether or not the infusion of two UCB units improves transplant outcomes is controversial and has been evaluated in a number of studies in both children and adults that are critically analyzed in this chapter. Two prospective randomized trials have been recently published in children and young adults up to 35 years of age that have clearly established the lack of benefit of dUCBT over an adequately sized single UCBT. However, in adult patients the relative role of dUCBT is much more controversial since the evidence is based on retrospective studies, including heterogeneous transplant platforms with different indications for transplant, conditioning regimens, GvHD prophylaxis, criteria for unit selection, and supportive care. Most studies found no benefit of dUCBT compared to sUCBT on any transplant outcome, at least when an adequately dosed single UCB unit was used. This raises the question of what adequately dosed means. Often, and without strong scientific support, an adequate cell dose is defined as a TNC dose >2.5 × 107/kg recipient body weight. There seems little or no theoretical, experimental, or clinical data supporting the dUCBT strategy. A randomized, double-blind trial is obviously needed. Unfortunately, this seems unlikely to be done.