Using a uniform detection method for donorspecific anti-HLA antibodies (DSAs), we sought to determine the effect of preformed DSAs on outcomes in double umbilical cord blood transplantation. DSAs were associated with an increased incidence of graft failure (5.5% vs 18.2% vs 57.1% for none, single, or dual DSA positivity; P ‫؍‬ .0001), prolongation of the time to neutrophil engraftment (21 vs 29 days for none vs any DSA; P ‫؍‬ .04), and excess 100-day mortality or relapse (23.6% vs 36.4% vs 71.4% for none, single, or dual DSA positivity; P ‫؍‬ .01). The intensity of DSA reactivity was correlated with graft failure (median of mean fluorescent intensity 17 650 vs 1 850; P ‫؍‬ .039). There was inferior long-term progression-free and overall survival when comparing patients with DSAs against both umbilical cord blood units to those without DSAs (3-year progression-free survival, 0% vs 33.5%, P ‫؍‬ .004; 3-year overall survival 0% vs 45.0%, P ‫؍‬ .04). We conclude that identification of preformed DSAs in umbilical cord blood recipients should be performed and that the use of umbilical cord blood units where preformed host DSAs exist should be avoided. (Blood. 2011; 118(25):6691-6697)

BACKGROUND Double cord blood transplantation (DCBT) offers an option for patients receiving reduced intensity transplants. These unique transplants have two donors, both of whom are usually HLA mismatched at 1–2 loci. STUDY DESIGN AND METHODS Forty-three patients were recipients of a reduced intensity DCBT. Cords were at least 4/6 allele level HLA-A, B, DR match with the patient and each other with minimum combined cell dose >3.7 × 107 TNC/kg. Twenty-one patients received cyclosporine/mycophenolate mofetil (CYA/MMF) and 22 patients received sirolimus/tacrolimus (SIR/TAC) for GVHD prophylaxis. The effect of allele level HLA typing on clinical endpoints of overall survival (OS), disease-free survival (DFS), engraftment, and acute graft versus host disease (aGVHD) were assessed. RESULTS Neutrophil (p=0.006) and platelet (p=0.033) engraftment were significantly faster in patients who have closer HLA-B allele-level matching to their cord blood units. Within the CYA/MMF protocol, closer HLA-DR matching had a trend for less aGVHD: using both cords in the analysis 21% vs 57%, p=0.053, and the predominant cord alone 30% vs 57%, p=0.143. There was a low incidence of aGVHD in the SIR/TAC group and no difference in aGVHD incidence was associated with HLA-DR mismatching. HLA-A, C and DQ had no effect on engraftment or aGVHD. CONCLUSION HLA-DR matching was associated with a trend for lower risk of aGVHD in patients treated with CYA/MMF. HLA-B matching was associated with faster neutrophil engraftment and faster platelet engraftment. High resolution HLA matching did not affect OS, DFS, nor did it predict which cord will become predominant.