Unrelated donor umbilical cord blood (UCB) transplants mismatched for either one or two human leucocyte antigens (HLAs)* offer adult patients with leukaemia similar outcomes to allele-matched bone marrow or peripheral blood progenitor cell (PBPC) transplants. This is the first analysis to show similar leukaemia-free survival in adults following matched bone-marrow or PBPC transplants and transplants of UCB. These findings, published Online First in The Lancet Oncology, support the use of UCB as a viable treatment option for adults with acute leukaemia for whom a bone-marrow or PBPC donor match cannot be found, or when a transplant is needed urgently.
Transplantation using an unrelated HLA-matched adult donor is the best alternative to an HLA-matched sibling. Yet, only 50% of white patients have access to an HLA-matched unrelated donor, and the likelihood of finding a matched donor is even lower for patients of non-white ethnic origin. Additionally, finding suitable adult donors and obtaining the stem cells can take months. As a result, UCB has become an increasingly attractive alternative to HLA-matched PBPC or bone marrow.
Transplantation using UCB is now a standard treatment option for leukaemia in children lacking HLA-matched sibling donors, but not in adults. Previous studies of UCB in adults have had conflicting results, and none have compared outcomes after transplantation from the three most commonly used graft sources—bone marrow, PBPC, and UCB—to establish which is the most effective in the treatment of adult leukaemia.
To provide more evidence, John Wagner from the University of Minnesota Blood and Marrow Transplant Program and international colleagues, analysed data from 216 transplant centres worldwide. They compared the outcomes of 165 adults aged 16 years or over with acute leukaemia who had transplantation with UCB, with 888 adults who had received unrelated PBPC transplants, and 472 who had been given unrelated donor bone marrow. The researchers also examined the effect of HLA-mismatch for all three graft sources.
After 2 years, leukaemia-free survival (LFS) was similar regardless of graft source. Interestingly, only disease status was linked to LFS—patients who were not in complete remission had higher treatment failure than those in complete remission.
Overall, UCB transplantation was linked with a generally lower rate of acute and chronic graft-versus-host disease (GvHD).
Additionally, transplant-related deaths were significantly higher after UCB transplants than after fully matched PBPC or bone-marrow transplants.
The authors say: "These results [for survival and rates of GvHD] are particularly noteworthy in view of the fact that 70% of UCB transplants were mismatched at two HLA antigens."
They conclude: "In the absence of a randomised clinical trial, these data support the use of 4/6 HLA matched unrelated UCB or 7/8 HLA-matched unrelated adult donor in the treatment of adults with acute leukaemia when an 8/8 HLA-matched unrelated adult donor is not available, and the use of UCB as first-line therapy when a transplant is needed urgently."
In an accompanying Comment, Paul Szabolcs from Duke University Medical Center, USA, says that this analysis highlights the importance of transplantation while a patient is in remission: "Clinicians should not waste time if it is thought that a patient is in imminent danger of progression, and should move towards cord-blood transplantation as long as a four-of-six HLA-matched unit is identified."
He concludes by calling for increased efforts to expand the inventory of public cord-blood banks and to boost the growth of living donor registries, particularly from minorities.
Professor John Wagner, University of Minnesota Blood and Marrow Transplant Program, Minneapolis, USA. T) +1 612 624 9912 E) wagne002@umn.edu
Dr Paul Szabolcs, Duke University Medical Center, Durham, USA. T) +1 919 668 1100 E) szabo001@mc.duke.edu
For full Article and Comment, see: http://press.thelancet.com/tloeapen.pdf
Notes to Editors: *Human leucocyte antigens (HLAs) are found on the surface of most cells and help the immune system distinguish between the self cells and non-self cells. HLA typing is used to match patients and donors for transplant to help prevent rejection of either the graft by the patient or the other way around.
Journal
The Lancet Oncology