According to a study, published Online First in The Lancet Oncology, transplant-related deaths could be considerably reduced by choosing recipients and donors who are better matched, compared to what is currently required for umbilical-cord blood transplantation. The discoveries should change standard practice in the way umbilical-cord blood recipients and donors are selected, and stress the importance for greater investment in public cord blood banks due to the significance of HLA matching on survival.
In order to prevent rejection, Human leukocyte antigen (HLA) testing is used to make sure recipients and donors are compatible. At present, adult donors are chosen from registries based on matching at four genes that rule tissue type - HLA A, B, C, and DRB1. However, to date, it was thought that umbilical-cord blood was able to tolerate differences between donors and recipients, currently the criteria for choosing unrelated cord-blood doesn't normally include matching HLA C.
At present, deaths following umbilical-cord blood transplantation are greater than after unrelated adult donor graft transplants. In order to lower this various different strategies are being researched.
Mary Eapen, from the Medical College of Wisconsin, Milwaukee, USA, and colleagues from the USA worked together with Eurocord, Hospital Saint Louis, Paris, France, and colleagues from Europe, in order to analyze the benefit of closer HLA matching. Collectively they looked back and evaluated the effect of donor-recipient HLA matching outcomes of 803 individuals (of whom most were under 16 years) with leukemia or myelodysplastic syndrome, who between 1996 and 2008 had undergone umbilical-cord blood transplantation in Europe and the U.S..
They discovered that further matching for HLA-C considerably reduced the number of transplant-related deaths following cord-blood transplants. The highest effects of HLA-C matching were achieved when there was no difference between the HLA antigen of the donor and recipient and also when there was only one HLA antigen difference.
2, 3 or 4 HLA antigen mismatches to any of the A, B, C, or DRB1 genes resulted in higher transplant-related deaths in comparison to none or a single mismatch.
The researchers explain:
"Our findings suggest that altering present selection strategies for umbilical-cord blood units might ameliorate some of the excess transplant-related mortality associated with umbilical-cord blood transplantation."
"Despite the substantial investment from governments to develop public cord blood banks, our findings support the need for even greater investment. The additional burden of HLA-C typing and the need to build an even larger inventory of cord blood units that will allow for matching at HLA C will add to the existing financial burden of the public-cord blood banks."
In an associated comment, Alois Gratwohl from the University of Basel, Basel, Switzerland, explains:
"These finding might be disappointing for some who thought minimal matching sufficient, but they have clear consequences. The degree of matching between donor and recipients, including HLA-C, needs to be integrated into the algorithm used to select for or against transplantation. This risk of disease should be balanced against the transplant risk, so that overall a better outcome with regard to survival, quality of life, and cost, compared with a non-transplant strategy, is achieved."
Written by Grace Rattue