Sibling Umbilical Cord Blood Infusion is Safe in Young Children with Cerebral Palsy

Abstract

Preclinical and early phase clinical studies suggest that an appropriately dosed umbilical cord blood (CB) infusion has the potential to help improve motor function in young children with cerebral palsy (CP). As many children with CP do not have their own CB available, use of allogeneic cells would extend access to this potentially beneficial therapy to more children. In this phase I, open-label study, 15 children, aged 1 to 6 years, with moderate to severe spastic CP were treated with a single intravenous infusion of allogeneic human leukocyte antigen (HLA) matched or partially matched sibling CB with a cell dose of ≥2.5 Â 10 7 cells/kg based on the pre-cryopreservation count (median infused cell dose, 3.3 Â 10 7 ; range, 1.8-5.2 Â 10 7 ). There were a total of 49 adverse events (AEs) over a 2-year time period, but there were no AEs related to the CB infusions. Specifically, there were no acute infusion reactions and no antibody formation against platelets, red blood cells, or donor-specific HLA antigens. Donor cells were not detected in peripheral blood 6 months later. Six months after infusion, participants were assessed for response and experienced a mean ± SD increase of 4.7 ± 2.5 points on the Gross Motor Function Measure-66 and 1 ± 2.9 points on the Peabody Gross Motor Quotient. Appropriately dosed, allogeneic partially or fully HLA-matched sibling CB infusion is well tolerated and potentially beneficial in young children with CP.cellular therapy, clinical trials, cord blood, human cord blood, nervous system, umbilical cord blood Lessons learned• Sibling umbilical cord blood (CB) infusions are well tolerated in young children with cerebral palsy (CP).• Although children treated with sibling CB demonstrated gains in motor function, this cannot be definitively attributed to CB treatment in this phase I study.• Randomized clinical trials are needed to determine efficacy of CB therapy and should evaluate the use of donor products.

Safety of allogeneic umbilical cord blood infusions for the treatment of neurological conditions: a systematic review of clinical studies

“…Study characteristics are provided in Table 1. While the authors' article was under review, the full trial results from Sun et al [28] were published. This study was included, and where duplicate publications existed (e. g., conference abstracts plus publication), the findings were reported only once and extracted from the primary source article.…”

“…All participant data from Vyas et al [27] were included in the results, regardless of condition. Of the 10 included studies, four were randomized controlled trials [18,20,22,26], five were single-group allocation studies [21,24,25,27,28] and one was a case report [19].…”

“…A total of 361 participants received allogeneic UCB as a study intervention with follow-up and safety outcomes collected. One study (n = 15) [28] specified that participants received related allogeneic UCB. The other studies either used unrelated UCB or did not specify donor source.…”

“…One study indicated that UCB that was not ABO blood group-matched was used, as units are commonly red blood cell-depleted [27]. The remaining six studies did not specify ABO matching [18,19,22,25,26,28].…”

“…In these studies, 106 participants received a single unit of allogeneic UCB with either a 4/6 (n = 53), 5/6 (n = 34) or 6/6 (n = 4) HLA match. Furthermore, 10 participants received 4/8 HLA-matched UCB, one received 5/8 HLA and four received 8/8 UCB [28]. Generally, HLA matching was specified as HLA-A, HLA-B and HLA-DRB1.…”