This analysis demonstrates that both donor file HLA diversity as well as search and donor selection practices have greatly improved from 2000–2005 with 44% of transplants being well-matched in 2000/2001 compared to 66% in 2004/2005. The NMDP required transplant centers to type patient/donor pairs at high-resolution HLA-A, -B, -C and -DRB1 starting in June 2005 (near the study end). The practice of HLA typing at the allele level including the HLA-C locus was already increasing at many centers. This new NMDP requirement may have assisted other centers to identify which donor options might be the best donor match. Some of the early year transplant pairs may have been considered a match based on standard HLA typing technology prior to transplant, then upon subsequent high-resolution testing were found to contain mismatches. This trend to better HLA matching is a success reflecting advances in the donor file diversity, improvement in typing technology, implementation of evidence-based recommendations, and donor selection strategy.13
Other factors have influenced the availability and selection of better matched donors. Greater transplant center experience and volume may improve a patient’s chances of transplanting with a well-matched donor. Small volume transplant centers have 20% greater likelihood of proceeding to transplant with a less-matched donor compared to high volume centers and are 28% more likely to choose a mismatched than a partially-matched donor. Improvements in HLA search strategy, early initiation of a search, and other factors may increase the chances of HCT with a better matched donor, even in less-experienced centers. Immunogenetic consultation may be of particular importance in these less-experienced transplant centers.
Patients with early stage leukemia had transplants with a mismatched donor less often than those with intermediate and late stage disease. This association could reflect either more urgent, late stage transplants with insufficient time to identify better matched donors or alternatively, no better donor identified during early stage and disease progression resulting in the transplant performed with two adverse factors – advanced stage and a lesser-matched donor.5
Since disease stage at transplant is a potentially modifiable factor based on clinical decisions, earlier searching with selection of the best matched donor and HCT at an earlier disease stage might be a preferred decision-making strategy, if no effective alternatives are available.
Extended duration searches have not been, and were not in this study, associated with transplantation using a better matched donor.14
This emphasizes the need to balance the patient’s disease status and urgency with donor matching. Longer search times may not yield better HLA matched donors. Regression analysis showed that patients transplanted more than 6 months from the initiation of donor searching were significantly (2.4 times) more likely to use a less-matched donor than those transplanted promptly (within 60 days of searching).
Transplant using a mismatch donor was less common for older patients. This may reflect deliberate physician decisions to avoid the added mismatch-associated morbidity and mortality in already higher risk, older recipients. The recent increase in transplants for older patients using reduced intensity treatment regimens are designed for better treatment tolerance. These reduced intensity transplants were more often performed using more stringent HLA-matching, perhaps defined by pre-specified protocol.
Patients from non-Caucasian racial groups were more often transplanted with lesser-matched donors. In this study, we evaluated only patients proceeding to transplant and did not address the recognized racial disparity in the likelihood of finding a suitable donor. Increased recruitment of donors from non-Caucasian racial and ethnic groups as well as specific decision-making about URD vs. alternate therapies, including umbilical cord blood HCT, is needed to further increase the likelihood of good outcome for patients potentially eligible for HCT.
International transplant centers were twice as likely to select a less-matched donor. For patients with uncommon HLA typing, accessing the NMDP’s diverse donor pool may have been the best option for the patient, possibly explaining, at least in part, this observation.
We have studied a unique aspect of donor searching, the association of patient non-HLA factors with selection of HLA matched stem cell donors. Based upon an assumption that the donor selected by the transplant center was the best available donor, we are encouraged that both availability and use of well-matched donors increased over the study interval, particularly for non-Caucasian racial and ethnic subgroups. Use of new advances, including the recent NMDP HapLogicSM match calculation algorithm, could further improve identification of better HLA matched donors for searching patients leading to more successful URD HCT.
These results identify statistically significant evidence of the impact of race, disease/stage, age and transplant center experience on the selection of HLA well-matched donors. We suggest that all centers should utilize current HLA strategy and worldwide resources available to aid in donor selection.14
Initiating a patient’s URD search early in the disease process, especially for patients from non-Caucasian racial and ethnic groups, will provide the best scenario for making informed transplant decisions. Additional focus on donor recruitment efforts and strategies, perhaps including umbilical cord blood, can help narrow the gap for non-Caucasian patient groups at increased risk of transplants with HLA mismatching.