Researchers from the University of Minnesota have reported that “transplantation of 2 partially HLA-matched UCB is safe and may overcome the cell-dose barrier that limits the use of UCB in many adults and adolescents.” The details of this report appeared in the February 1, 2005 issue of Blood .

Allogeneic stem cell transplants are an important component of the treatment of adults with acute leukemia and other hematologic diseases. The first choice for a donor of stem cells is an HLA-matched relative; however, such an ideal donor is only available for a minority of patients, resulting in the need to expand the donor pool. It has been determined that related donors who are mismatched for only one HLA antigen are also suitable stem cell donors. Over the past two decades, there has been a marked increase in the number of unrelated donor transplants, with outcomes similar to those achieved with related donor transplants. However, because of genetic disparity, unrelated matched donors cannot be found for many patients, especially for those with unusual HLA types, such as those found in many minority populations. In addition to the genetic problem, many patients die while seeking an unrelated donor, which can be a lengthy search process. Umbilical cord blood (UCB) offers an alternative source of stem cells that are immediately available and there is evidence that the degree of mismatching for HLA antigens is not as important as it is for marrow or blood stem cells. This leads to less graft rejection and less graft-versus-host disease. The major limitation of UCB transplants is the low stem cell number with resultant delayed or absent engraftment. There has been skepticism that single units of cord blood would be adequate for full engraftment in adults. However, recent studies in adults have suggested that single UCB units are an acceptable source of stem cells for small to average sized adults. One solution to the low stem cell dose in UCB units is to use multiple UCB units. However, there are theoretical problems with this concept including a possible graft-versus graft reaction where each graft destroys each other.

This study evaluated two partially HLA-matched stem cell transplants in 23 patients with advanced acute lymphocytic leukemia, acute myeloid leukemia or chronic myeloid leukemia who were an average of 73 Kg, with the heaviest patient being 120 kg. The median time to recovery of neutrophils was 23 days, with all patients recovering by day 41 after transplantation. The median time to recovery of platelets to 50,000 was approximately 3 months. Survival at one year was approximately 80% for those transplanted in remission and 20% for those transplanted in relapse. They also reported that the UCB unit with the higher CD3+ cell number ultimately engrafted and cells from the other unit ultimately disappeared. Cells from one of the two units predominated in all cases by day 100, but early contribution to engraftment was from both units.

Comments: These data show that transplantation of two UCB units is feasible and may improve the speed of engraftment in larger individuals. However, this is speculative since this was not a randomized trial. Since there is reluctance to use single UCB units in larger individuals, it is unlikely that a randomized trial will ever be performed. More experience will probably be gained at this and other institutions with two UCB units in large adults to confirm these observations.

Reference: Barker JN, Weisdorf DJ, DeFor TE, et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005;105:1343-1347.