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Improvements in Unrelated Donor Transplantation

Unrelated donor transplant outcomes have improved in the last decade and recent studies have shown similar outcomes for unrelated donor and sibling donor transplantation in certain diseases and patient populations. For a description of some of these studies, see Comparing Unrelated Donor to Sibling Donor Transplant. Key factors in improved unrelated donor transplant outcomes are discussed below.

More precise HLA matching

The outcomes of unrelated donor or cord blood transplants are strongly affected by the degree of HLA matching between the donor and transplant recipient. HLA matching plays an important role in engraftment, incidence of graft-versus-host disease (GVHD) and overall survival. More precise matching is now possible because:

DNA-based tissue typing enables typing at a higher resolution.
The understanding of matching criteria, including which HLA loci are most significant to outcomes, has improved and continues to be refined.

For details, see Advances in HLA Typing.

Improving the donor search process

Searching the National Marrow Donor Program (NMDP) Registry for a matched unrelated donor is faster, more efficient and more likely to yield a suitably matched donor or cord blood unit than ever before. The increased likelihood of finding a match is due in large part to the growth of the NMDP Registry, which currently has more than 6.9 million adult marrow and PBSC volunteers and more than 73,000 cord blood units (February 2008 figures).

Increased speed and the improved efficiency of searches are the result of the NMDP’s new enhanced matching algorithm that identifies the donors or cord blood units (CBU) with the highest potential to match the patient. This allows transplant physicians searching the NMDP Registry to more quickly and efficiently identify the best immunogenetically matched donor or CBU for their patients.

The new matching algorithm, named HapLogic^SM by the NMDP, is based on analyses of the haplotypes of millions of donors on the NMDP Registry. HapLogic uses advanced logic to predict a donor’s or CBU’s high-resolution match, and builds upon mathematical formulas that predict DR match in AB-typed donors. [1]

The improved search algorithm is one of several advances in the search process for transplants facilitated through the NMDP. Searching for an unrelated donor through the NMDP also means that physicians have a single point of access for all three sources of hematopoietic cells.

Expanded sources of cells for transplant

Today physicians working with the NMDP can select from three potential hematopoietic cell options for patients in need of an unrelated donor — marrow, cells from peripheral blood and umbilical cord blood.

A phase III randomized multicenter trial is underway to determine whether hematopoietic cells from the marrow or peripheral blood offer advantages to patients. The study protocol is available from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Web site. [2]
Cord blood transplants with up to 2 HLA antigen mismatches between the cord blood unit and the recipient have shown survival outcomes similar to those for 6 of 6 HLA-matched unrelated donor marrow transplants. [3,4]

For further information on using an NMDP cord blood unit, see Likelihood of Finding an Unrelated Donor or Cord Blood Unit.

Impact of transplant timing on outcomes

Appropriate timing of the transplant is a critical factor in improved patient outcomes. For most diseases, transplants performed early in the disease process are associated with lower TRM and disease recurrence. For example, in a 2007 study of 3,857 unrelated donor transplants, patients with intermediate-stage disease had a 38% greater risk of mortality than patients with early-stage disease. Patients with advanced disease had approximately twice the mortality risk as patients with early-stage disease. [5]

In an analysis of 1,180 patients transplanted for leukemia or other hematological malignancies from before 1990 to 2002, Bacigalupo et al. found that with the changes in transplant over time, for patients transplanted in first remission, TRM has been significantly reduced and 2-year survival significantly improved. However, for patients transplanted in second remission or relapse there has been little to no reduction in TRM or improvement in survival. [6] Several studies, for example two studies of transplant for CML and one of transplant for acute leukemias, have shown more significant differences in survival based on the timing of transplant than on whether the donor was a sibling or an unrelated volunteer. [4,6,7]

For further discussion of the impact of timing on outcomes, see Transplant Outcomes by Disease and Disease Stage.

References

Hurley CK, Wagner JE, Setterholm MI, Confer DL. Advances in HLA: Practical implications for selecting adult donors and cord blood units. Biol Blood Marrow Transplant. 2006; 12(1) Suppl. 1:28-33.
http://www.bbmt.org/article/PIIS1083879105006890/abstract
BMT CTN Protocol 0201 - A Phase III randomized multicenter trial comparing G-CSF mobilized peripheral blood stem cell with marrow transplantation from HLA compatible unrelated donors.
https://web.emmes.com/study/bmt/protocol/
0201__protocol/0201__protocol.html
Grewal SS, Barker JN, Davies SM, Wagner JE. Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood. 2003; 101(11):4233-4244.
http://www.bloodjournal.org/cgi/content/full/101/11/4233
Wagner JE, Barker JN, DeFor T, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood. 2002; 100(5):1611-1618.
http://www.bloodjournal.org/cgi/content/full/100/5/1611
Lee SJ, Klein J, Haagenson M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007; 110(13):4576-4583.
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/110/13/4576
Bacigalupo A, Sormani MP, Lamparelli T, et al. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation. Haematologica, 2004; 89(10):1238-1247.
http://www.haematologica.org/cgi/content/abstract/89/10/1238
Eapen M, Rubinstein P, Zhang MJ, et al. Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months. J Clin Oncol. 2006; 24(1):145-151.
http://www.jco.org/cgi/content/abstract/24/1/145