Donor Characteristics Affecting Graft Failure and Survival after Unrelated Donor Transplantation with Reduced Intensity Conditioning Regimens (RIC) for Hematologic Malignancies.

Impact of donor characteristics is well described for standard intensity unrelated donor and matched sibling donor transplants but may differ in recipients of unrelated donor RIC transplants. Less immunosuppressive regimens at transplantation may lead to higher graft failure rates. We examined risk factors affecting graft failure, acute and chronic graft-versus-host disease (GVHD) and survival after RIC unrelated donor transplants in 715 patients with acute (n=394) and chronic leukemia (n=74), myelodysplastic syndrome (n=70) and non-Hodgkin lymphoma (n=177). Graft failure was defined as <5% donor chimerism within 3 months after transplantation. 159 patients received bone marrow (BM) and 556 peripheral blood (PB) grafts. All transplantations occurred in 1999–2006 in the US. Median follow-up of surviving patients was 36 months (range 6–92). All donors and recipients were typed for HLA A, B, C and DRB1 using high resolution molecular methods. Mismatches at low resolution (antigen) and high resolution (allele) were considered together and are described collectively as mismatches. The day-28 incidence of neutrophil recovery (≥ 0.5 x 10⁹/L) was 96%. After initial neutrophil recovery most patients (n=506) had >95% donor chimerism. 63 patients had <5% donor cells and the remaining 146 patients, 5–95% by 3-months post-transplant. In multivariate analysis, the only factor associated with graft failure was transplantation of BM vs. PB grafts (odds ratio 2.36, p=0.002). We specifically looked for an effect of donor-recipient sex match on graft failure and female donor parity on GvHD and found none. As expected risks of acute graft-versus-host disease (GVHD) were higher after mismatched transplants (p=0.015). No donor characteristic was associated with chronic GVHD. The only donor characteristic affecting overall survival was donor-recipient HLA disparity: 3-year overall survival rates were significantly lower at 23% after mismatched transplants compared to 42% after HLA-matched transplants (p=0.008). Additionally, mortality rates were significantly higher in patients older than 50 years (p=0.005), performance score <90 (p=0.002) and when transplantation occurred with active disease (p<0.001). As seen in recipients of myeloablative conditioning regimens, the only donor characteristic associated with survival is donor-recipient HLA disparity. Donor age, donor-recipient sex match, donor parity and donor cytomegalovirus serostatus were not associated graft failure or survival after unrelated donor RIC transplants.