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HLA-matched donors available for most HSCT candidates
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A majority of hematopoietic stem-cell transplantation candidates who do not have related donors have suitable adult donors or cord-blood units through the National Marrow Donor Program’s registry, according to results of a modeling study.
However, the availability of matched unrelated donors varied among racial and ethnic groups, and few patients would have optimal donors, results showed.
“The question on the likelihood of finding a match in the registry is difficult to answer,” Martin Maiers, director of bioinformatics research at the National Marrow Donor Program, told HemOnc Today. “Many donors in the registry don’t have HLA typing at the clinical matching resolution. The main innovation in this study was to build on a modeling technique that uses population genetics as the foundation to project these matching rates at the clinical resolution to answer that question.”
Martin Maiers
Maiers and colleagues evaluated HLA data from the National Marrow Donor Program, which includes the C.W. Bill Young Cell Transplantation Program and the Be the Match Registry. The complete registry included more than 10 million adult donors and 186,166 cord-blood units in 2012, and researchers anticipated 9% cumulative growth each year from 2013 to 2017.The researchers used population-based genetic models for 21 racial and ethnic groups to calculate the likelihood that patients would find suitable adult donors or cord-blood units for HSCT.
The researchers used population-based genetic models for 21 racial and ethnic groups to calculate the likelihood that patients would find suitable adult donors or cord-blood units for HSCT.
Potential adult donors were an optimal 8/8 HLA match if they had matching HLA-A, HLA-B, HLA-C and HLA-DRB1 loci. Cord-blood units were an optimal 6/6 HLA match if they had antigen-level HLA-A and HLA-B matching and high-resolution HLA-DRB1 matching.
The model followed clinical protocol to assess whether patients would have suitably matched adult donors before seeking cord-blood unit matches.
The analysis indicated most patients would have a 7/8 or 8/8 HLA-matched unrelated adult donor in the registry. The projected likelihood was highest for white European patients and varied according to race and ethnicity (see Table).
Source: Adapted from: Gragert L. N Engl J Med. 2014;doi:10.1056/NEJMsa1311707.
The likelihood of finding matched cord blood units also varied according to race and ethnicity, yet patients aged younger than 20 years had a greater likelihood of finding optimal or suitable matches.
“The overall result is good news — there is some sort of suitable match for most patients searching the registry,” Maiers said. “However, there is still a call to action. Although we have an option for almost everyone, the goal is really to find an optimal match. In addition, minority donors are where the need is the greatest.”
Efforts are ongoing to improve minority donor recruitment and retention, Maiers said. Researchers also are conducting additional studies to assess the accuracy of ethnic and racial self-identification, as well as to determine how multiracial ancestry should be incorporated into genetic models.
Yet, the high likelihood that most patients will find at least a suitable match in the registry reflects the efforts to improve recruitment and establish cord-blood banks, Maiers said.
“We believe that with these numbers and the projection of matches, it’s important not to delay transplant for a more suitable match, because time is often working against the patient,” Maiers said. “In the early days of the registry, it was typical to wait because recruitment was contributing a large percentage of the overall registry. Now, transplanting with a mismatched transplant is a better way to go given the diminishing likelihood that the miracle match will register in the next round of recruitment. This study supports taking a mismatch today vs. waiting for the possibility of an optimal match tomorrow.” – by Alexandra Todak
Reference:
Gragert L. N Engl J Med. 2014;doi:10.1056/NEJMsa1311707.
For more information:
Martin Maiers can be reached at National Marrow Donor Program/Be the Match, 3001 Broadway St. NE, Suite 100, Minneapolis, MN 55413; email: mmaiers@nmdp.org.
Disclosure: The study was funded in part by a grant from the Department of the Navy’s Office of Naval Research, and a contract with the C.W. Bill Young Cell Transplantation Program, part of the Department of Health and Human Services’ Health Resources and Services Administration. Maiers reports grant support from the Office of Naval Research. See the study for a list of the other researchers’ relevant financial disclosures.
Perspective
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Sergio A. Giralt, MD
In the 1970s, E. Donnall Thomas, MD, published the results from the first 100 patients with acute leukemia who had failed primary therapy and underwent transplant, and a quarter of them were cured. This was a watershed moment. At that time, patients with marrow diseases — such as aplastic anemia, acute leukemia and myeloma — could be cured if they had a matching brother or sister. Generally speaking, in a population in which the average family has two or three children, there is a 30% chance of having a matched sibling in your family.Fast forward to the 1980s: When transplant was recognized as a curative modality for a number of hematologic malignancies, not having a donor in the family presented the most important barrier to access. Because of emerging knowledge of population genetics and HLA typing, it was felt that a registry of volunteer donors that was large enough would be able to provide matches for people who did not have matching brothers and sisters.
That is how the National Marrow Donor Program (NMDP) began. The NMDP and International Blood and Marrow Transplant Registry (IBMTR) partnered 10 years ago to form the Center for International Blood and Marrow Transplant Research (CIBMTR) to perform prospective and retrospective studies that would advance the field of stem cell transplantation. The NMDP and the CIBMTR have really fulfilled their goals and have gone above and beyond the call of duty. The paper by Maiers and colleagues is just one example of the type of research these two organizations have been able to put together.
The paper suggests that we should be able to find an adequate stem cell source for almost anybody who has a disease that can be cured with transplant. Yet, a fully matched stem-cell source is only available for three-quarters of patients of white European background, and for 40% to 50% of patients from other backgrounds. In some specific mixed-ethnic backgrounds, the perfect cell source will only be found for 30% to 40% of patients. It is important to continue to study to find ways to improve transplant outcomes of less-than-perfect cell sources, because less-than-perfect matches are associated with more complications than perfect matches.
Resources utilized in expanding donor sources have been effective in increasing the number of transplants. As cord blood banks and donor registries have increased, the number of transplants performed across the world has also increased. People who otherwise would not have undergone transplant are now going to transplant.
Yet, these resources — both the registry and the cord blood bank — need to be managed prospectively in a more cost-effective way. It makes no sense to go out and campaign to get more white European donors, because it’s not going to increase the likelihood of a white European donor finding a match. However, it makes a lot of sense to try to find more donors in the minority ethnic groups, and it particularly makes sense to target the mothers represented in the minority ethnic groups to get their cord blood, because there are patients who need the cord blood from this patient population.
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