Optimizing selection of double cord blood units for transplantation of adult patients with malignant diseases
Giancarlo Fatobene, Fernanda Volt, Frederico Rafael Moreira, Lívia Mariano, Patrice Chevallier, Sabine Fürst, Hélène Labussière‐Wallet, Régis Peffault de la Tour, Éric Deconinck, Thomas Cluzeau, Nigel H. Russell, Dimitrios Karakasis, Édouard Forcade, Annalisa Ruggeri, Éliane Gluckman, Vanderson Rocha
Abstract
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 × 107/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 CD34+ cell dose ≥0.7 × 105/kg in the winning UCB was associated with improved OS (HR, 1.34; P = .03). Low TNC (≤3.5 × 107/kg) and CD34+ (≤1.4 × 105/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 associated with increased transplant-related mortality. Our data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose >3.5 × 107/kg and CD34+ cell dose of ≥0.7 × 105/kg per unit in DUCBT candidates.