Development and production of allogeneic cord blood-derived red blood cell concentrates for transfusion to extremely preterm neonates, the All-Cord study

Background: 

Extremely preterm neonates often require red blood cell (RBC) transfusions derived from adult donors. These transfusions introduce adult hemoglobin into a neonatal hematopoietic system dominated by fetal hemoglobin (HbF), shifting the oxygen-dissociation curve and increasing oxygen delivery to immature tissues. This contributes to oxidative stress and has been associated with prematurity-related diseases. Cord blood (CB)-derived red cell concentrates (CB-RCCs) offer a new physiological alternative by preserving HbF. To enable clinical implementation, CB-RCCs must meet (inter)national quality standards. This study investigated the impact of pre-filtration dilution, storage in non-di(2-ethylhexyl)phthalate (DEHP) plasticized bags, and three additive solutions—saline-adenine-glucose-mannitol (SAGM), phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM), and SOL-X—on CB-RCC quality over 21 days. 

Study Design and Methods: 

CB was collected after term delivery and processed within 24 h into leukocyte- and platelet-depleted CB-RCCs. Products, either pre-filtration diluted or undiluted, were stored up to 21 days in 1,2-cyclohexane dicarboxylic acid diisononyl ester- or DEHP-plasticized polyvinyl chloride bags containing SAGM, PAGGSM, or SOL-X additive solutions. Quality parameters were assessed on Days 1, 7, 14, and 21. Quality standards were compared against (inter)national requirements for adult RCC. 

Results: 

Pre-filtration dilution to maximize yield was found to impair product quality. CB-RCCs stored in non-DEHP bags with PAGGSM showed the lowest hemolysis at Day 21 (0.30 ± 0.09%), outperforming SAGM (0.57 ± 0.16%). Red blood cells in non-DEHP bags also preserved adenosine triphosphate levels and deformability better than in DEHP bags. 

Discussion: 

We demonstrated that CB-RCCs stored in non-DEHP bags with PAGGSM as an additive solution meet (inter)national Blood Bank quality standards up to 21 days of in vitro storage.