Optimizing selection of double cord blood units for transplantation of adult patients with malignant diseases

Double-unit unrelated cord blood transplantation (DUCBT) is an option in patients for whom a single unit is not sufficient to provide an adequate number of cells. As current guidelines on UCB unit selection are mainly based on single-unit UCB data, we performed a retrospective analysis of 1375 adult recipients of DUCBT for hematologic malignancies to determine optimal criteria for graft selection. Cryopreserved total nucleated cells (TNCs; <3.5 vs.3.5 X 10(7)/kg: hazard ratio [HR], 1.53; 30% vs 45%; P=.01), number of HLA mismatches (>= 2 vs 0-1: HR, 1.28; 42% vs 48%; P=.01), and ABO compatibility (minor/major ABO incompatibility vs compatibility: HR, 1.28; P=.04) were independent risk factors for OS. Cryopreserved CD341 cell dose >= 0.7 X 10(5)/kg in the winning UCB was associated with improved OS (HR, 1.34; P=.03). Low TNC (<3.5 X 10(7)/ kg) and CD34(+) (<1.4 X 10(5)/kg) cell doses were related to decreased neutrophil recovery ( HR, 0.65 [P=.01] and HR, 0.81 [P=.01], respectively). DUCBT recipients with >= 2 HLA mismatches had a higher incidence of grade II-IV and III-IV acute graft-versus-host disease (HR, 1.26 [P=.03] and 1.59 [P=.02], respectively). Low TNC dose (HR, 1.57; P=.02) and receiving UCB with >= 2 HLA mismatches (HR, 1.35; p=.03) were associatedwith increased transplant-related mortality. Our data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose.3.5 X 10(7)/kg and CD341 cell dose of >= 0.7 X 10(5)/kg per unit in DUCBT candidates.