Grafts from younger, HLA-matched donors may improve HSCT outcomes

Factors such as donor age and donor–recipient HLA-match appeared to contribute to long-term survival among patients undergoing unrelated-donor transplantation for hematologic malignancies, according to study results published in Blood.

However, other variables — including sex, parity and cytomegalovirus serostatus — did not appear associated with long-term outcomes, according to the researchers.

The number of unrelated hematopoietic stem cell transplantations (HSCT) are increasing, according to study background. However, the prime strategy for prioritizing donors among comparably HLA-matched potential donors has not been determined.

Thus, Mary Eapen, MBBS, MS, professor of medicine at Medical College of Wisconsin in Milwaukee, and colleagues sought to observe the association between donor characteristics and survival after HSCT for patients with hematologic malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia and myelodysplastic syndrome.

OS served as the primary endpoint.

The researchers established a training cohort (1988-2006; n = 6,349) and validation cohort (2007-2011; n = 4,690) using datasets from The Center for International Blood and Marrow Transplantation. Median donor age was 35 years (range, 18-61).

All donor–recipient pairs had allele-level HLA typing at HLA-A, -B, -C and –DRB1, which serves as the current standard for selecting donors. In the training cohort, 59% of donor–recipient pairs were 8/8 matched and 43% were ABO blood-group matched. In the validation cohort, all pairs were 8/8 or 7/8 HLA matched.

In both cohorts, older donors had a higher likelihood of being mismatched to their recipients, to be cytomegalovirus seropositive, and to donate grafts with lower cell dose compared with younger donors (P < .001 for all).

In multivariate analyses adjusting for patient disease and transplantation characteristics, factors associated with mortality included donor age of 33 to 55 years (HR = 1.13; 95% CI, 1.05-1.2), age older than 50 years (HR = 1.29; 95% CI, 1.14-146), 7/8 HLA match (HR = 1.24; 95% CI, 1.15-1.24) and lower HLA matches.

Older donor age (P = .01) and lower HLA match (P .001) also appeared associated with an increased risk for graft-versus-host disease.

These associations persisted regardless of disease, disease status at transplantation, donor sex, parity, patient age, performance score, graft type or transplantation period.

The validation cohort confirmed these findings. For every 10-year increment in donor age, researchers observed a 5.5% increase in the HR for overall mortality after adjusting for other factors.

Patients with a 7/8 HLA-matched donor in the validation cohort also had an increased risk for mortality (HR = 1.37; 95% CI, 1.25-1.51).

Data from the training cohort indicated patients who received grafts from older donors had higher rates of nonrelapse mortality. Tested as a continuous variable, increasing age correlated with a higher risk for nonrelapse mortality (HR = 1.005; 95% CI, 1.001-1.01).

However, donor age was not associated with the risk for relapse.

“Our findings support including donor age to the selection algorithm,” Eapen and colleagues wrote. “We acknowledge the likelihood of identifying a fully HLA-matched donor for non-Caucasians is substantially lower than for Caucasians and incorporating donor age to the selection algorithm may mitigate some of the excess mortality associated with HLA-mismatched transplantations. ... Alternative donors such as unrelated umbilical cord blood and haploidentical related donors should ensure patients with rare HLA genotypes are not denied access to transplantation.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.