Expanded Access Protocol of Umbilical Cord Blood Infusion for Children with Neurological Conditions

Abstract

Introduction Intravenous infusion of banked autologous and sibling umbilical cord blood (CB) is being studied in children with acquired neurological conditions and has demonstrated safety and feasibility in phase I/II studies. To provide access to this investigational procedure while efficacy trials are conducted, an expanded access program (EAP) was developed. Objective The aim is to report early outcomes of a single center EAP enabling infusion of autologous/sibling CB for children with acquired neurological conditions. Methods A protocol for CB infusion utilizing established standard operating procedures was filed under Investigational New Drug #15949. Potentially eligible children with autism, cerebral palsy, and related conditions were screened remotely under a screening protocol via parental questionnaires, medical records, and labs. Children with genetic syndromes, immunodeficiencies, or medical fragility were ineligible. Autologous/sibling CB units (CBUs) were qualified to ensure a pre-cyropreservation total nucleated cell count (TNCC) >1 x 107/kg, viability >70%, negative sterility cultures, and negative maternal donor screening tests. Sibling pairs had to be at least haploidentical by human leukocyte antigen. A segment of each CBU was tested for viability, potency, and identity confirmation. On the day of infusion, recipients were premedicated with intravenous diphenhydramine and methylprednisolone. The CBU was thawed, washed, and infused over 10 minutes via peripheral IV. When the TNCC permitted, CBUs could be divided for repeated doses. Results More than 1,400 children have enrolled in the screening protocol to date. From November 2017 to June 2019, 276 children received 302 CB infusions under the EAP. Table 1 shows recipient and CB characteristics. Median pre-cryopreservation TNCC of CBUs was 7.8 × 108, and median infused dose was 2.5 × 107/kg. Infusions were well tolerated. The only related adverse events were transient infusion reactions, which occurred with 3.9% of infusions (n = 12, one serious adverse event). Despite negative sterility cultures pre-cryopreservation, there were 6 (2%) positive cultures post-thaw. No child required treatment or developed an infection post-infusion. One-year follow-up questionnaires were completed by 54 of 83 (65%) families. Parental assessment of clinical improvements varied. Discussion An EAP including procedures for remote screening of patients and CBUs was developed to provide access to autologous/sibling CB infusion for children with acquired neurological conditions. In general, CB infusions have been safe and feasible, with variability in parent-reported outcomes. Standard phase II/III clinical trials will be required to evaluate efficacy.