Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation

Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation

Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia.

IMPORTANCE: Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity. OBJECTIVE: To evaluate the association between recipient and donor pre-transplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia DESIGN, PARTICIPANTS, AND SETTING: The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond Blackfan anemia) and their unrelated donors who had pre-HCT blood samples, and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers, and were followed-up until March 2013 EXPOSURES: Recipient and donor pre-HCT leukocyte telomere length classified into long (3(rd) tertile) and short (1(st) and 2(nd) tertiles combined) based on donor telomere length distribution. MAIN OUTCOMES: Overall survival, neutrophil recovery, and acute and chronic graft-versus-host disease (GvHD), as ascertained by transplant centers through regular patient follow-up. RESULTS: Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival=56% (number at risk=57, cumulative deaths=50 vs. 40% (number at risk =71; cumulative deaths=128), in the long vs. short, respectively; p=0.009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race, and calendar year of transplant (hazard ratio (HR)= 0.61, 95% confidence intervals=0.44–0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence= 86% vs. 85%; HR=0.94, 95% CI= 0.73–1.22), acute GvHD grades III–IV at 100 days (cumulative incidence =22% vs. 28%; HR=0.77, 95% CI= 0.48–1.23), or chronic GvHD at 1-year (cumulative incidence =28% vs. 30%; HR=0.81, 95% CI= 0.53–1.24) for long versus short respectively. Pre-transplant leukocyte telomere length in the recipients was not associated with post-transplant survival (HR= 0.91, 95% CI= 0.64–1.30). CONCLUSIONS AND RELEVANCE: Longer donor leukocyte telomere length was associated with increased 5-year survival in patients who received HCT for severe aplastic anemia. Patient leukocyte telomere length was not associated with survival. The results of this observational study suggest that donor leukocyte telomere length may have a role in long-term post-transplant survival