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

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.

Impact of allele-level HLA matching on outcomes after double cord blood transplantation in adults with malignancies

“…The results obtained in the present study using this approach were concordant with analyses restricted to the winning unit. 6 Considering the worst matched unit allows to study the effect of HLA mismatching on graft failure and early TRM while also considering the potential influence of the second unit on these outcomes by considering the two-unit TNC and CD34+-cell dose. However, such an approach has the caveat of disregarding the eventual impact of HLA mismatching of the better matched CBU if it becomes the winning unit.…”

Unrelated umbilical cord blood can improve the prognosis of haploidentical hematopoietic stem cell transplantation

“…Initially, UCB transplantation (UCBT) was used in children and achieved satisfactory outcomes [19]. Because UCB has few CD34 + cells, new approaches, such as the use of double UCBT (dUCBT), have been used in adult patients to avoid a prolonged delay in immune reconstitution [20]. The progress of UCBT was also summarized in a review [21].…”

Unrelated umbilical cord blood can improve the prognosis of haploidentical hematopoietic stem cell transplantation

“…Initially, UCB transplantation (UCBT) was used in children and achieved satisfactory outcomes [19]. Because UCB has few CD34 + cells, new approaches, such as the use of double UCBT (dUCBT), have been used in adult patients to avoid a prolonged delay in immune reconstitution [20]. The progress of UCBT was also summarized in a review [21].…”