Feasibility and safety of autologous cord blood derived cell administration in extremely preterm infants: a single-centre, open-label, single-arm, phase I trial (CORD-SaFe study)

Background: Evidence from preclinical studies in small and large animal models has shown neuroprotective effects of intravenous administration of umbilical cord blood derived cells (UCBCs). This study aimed to evaluate the feasibility of umbilical cord blood (UCB) collection, extraction of UCBCs, and subsequent safety of intravenous autologous administration of UCBCs in extremely preterm infants (born <28 weeks gestation). Methods: A single-centre, open-label, single-arm, safety and feasibility clinical intervention trial was conducted at Monash Medical Centre and Monash Children's Hospital, Melbourne, Australia. Participants were extremely preterm infants born at less than 28 weeks completed gestation, and exclusions included major congenital malformation, maternal blood-borne virus infection, and severe brain injury on postnatal cranial ultrasound. UCB was collected at birth, and UCBCs were characterised (total nucleated cell count (TNC), mononuclear cell count (MNC), CD34+ cell count) and cryopreserved. Infants were reinfused with autologous UCBCs (25–50 million MNCs/kg) intravenously in the second postnatal week. Primary outcomes included feasibility: sufficient UCB volume (>7 mL) and UCBC numbers following processing (>25 × 10⁶ TNCs/kg); and safety: absence of adverse events directly related to UCBC administration. Findings: Forty-four UCB collections were attempted and sufficient UCB volume/UCBC extraction was demonstrated in 37 (84.1%) infants. Good Manufacturing Practice (GMP) grade cells were obtained in 31/44 (70.4%) of infants. Median (IQR) TNCs and MNCs collected were 130 (67–207) x 10⁶/kg and 60 (39–105) x 10⁶/kg, respectively. 23 infants with median (IQR) gestation of 26 (24–27) weeks and birth weight of 761 (650–946) grams were administered cells at a median (IQR) dose of 42.3 (31.1–62.3) x 10⁶ MNCs/kg). No serious adverse events were noted, and the infusions were well-tolerated. Interpretation: This phase-1 clinical trial has shown UCBC collection and reinfusion was feasible in approximately 70% of extremely preterm infants and was well tolerated without any serious adverse events. Funding: Funding to support this study was obtained fromNational Health and Medical Research Council of Australia,Cerebral Palsy Alliance,National Stem Cell Foundation of Australia, andLions Cord Blood Foundation.