In the present study the cumulative incidence of engraftment seems to be unaffected by the presence of DSAs in patients transplanted with two partially HLA-matched UCB units. Unlike previous reports in the context of adult unrelated donor allogeneic HCT 3
and single-unit UCB transplantation 4
, the presence of DSAs targeting one or both UCB donor units failed to impair engraftment or affect which unit predominated over the long-term. In a study by Takanashi et al. 4
, the incidence of neutrophil recovery was only 32% among 20 patients with a DSA directed against the UCB donor unit. Similar results were observed by Spellman et al. 3
in the context of adult unrelated donor allogeneic HCT, where in 9 of 10 patients with a DSA the donor graft failed, and by Ciurea et al. 2
in the context of haploidentical transplantation, where in 3 of 4 patients with a DSA the donor graft failed. In contrast, the majority of the 18 patients (78%) in our study achieved long-term engraftment despite testing positive for a DSA against one or both UCB units. While it could be speculated that our patients were protected from graft failure by the presence of two UCB units, this may be the only reason for the differences in outcome because engraftment was observed in 5 of 6 (83%) patients with antibodies directed against both units. However, in the first 12 patients, 7 of 10 evaluable patients (excluding one patient with early death and the one with autologous recovery) engraftment occurred with the unit against which there was no DSA. Thus, it is possible that while immediate rejection of units against which there is a DSA does not occur, that DSA could be associated with failure to engraft long-term favoring engraftment of the unit that did not have DSA against. One limitation of the present study is the absence of analysis for DSA against HLA-DPB1. It remains possible that antibodies directed against DP or other antigens on UCB influence graft failure or unit predominance. Taken together, our data suggest that donor-specific HLA alloresponses, may not increase the risk of graft failure in dUCB transplantation. It remains to be determined in larger number of patients whether or not DSA influences unit predominance after dUCB transplantation. While screening for DSAs is certainly feasible 11
, it could add to health care costs, delay donor acquisition, and may lead to the selection of a donor unit with a lower cell dose or greater HLA mismatch, all of which are factors proven to negatively impact survival. While we recognize that limited numbers of patients may have prevented our ability to detect the impact of anti-HLA antibodies and that different conditioning regimens and post-transplant immunosuppressive therapies may have altered our results, currently we cannot recommend routine anti-HLA antibody screening for UCB unit selection in the setting of dUCB transplantation as this practice could result in the selection of less suitable units. Additional data, in larger numbers of patients, are required to establish a clear association between DSA and graft failure or unit loss in the setting of dUCB transplantation.