Abstract 5 Umbilical Cord Blood Treatment to Improve Gross Motor Function in Individuals with Cerebral Palsy: Results from an Individual Participant Data Meta-Analysis

Abstract Introduction Umbilical cord blood (UCB) is a novel treatment for cerebral palsy (CP) with clinical trials indicating UCB is safe and can improve gross motor function. However, heterogeneity across research design, participant selection and treatment protocols has limited the ability to interpret overall treatment effect, identify best responders and dosing thresholds. Objectives We sought to conduct a systematic review and individual participant data meta-analysis (IPDMA) to 1) determine the effect of UCB treatment measured by Gross Motor Function Measure (GMFM) in individuals with CP, and 2) determine the effect of UCB cell dose on clinical improvement. Methods CENTRAL, Embase and Medline were systematically searched for clinical studies administering UCB to individuals with CP with or without a control group/comparator, collecting GMFM scores at baseline and 1, 3, 6 and/or 12 months. Individual de-identified participant data were obtained before being cleaned and coded. A one-stage IPDMA was conducted in R to obtain the pooled effect of UCB and the pooled cell dose effect via linear mixed models, including random effects terms to investigate between-study heterogeneity. Results Individual participant data from nine published and two unpublished studies (seven RCTs and four single-arm studies) were obtained, comprising 285 UCB (+/- erythropoietin, EPO)- treated participants and 171 controls for analysis. Median baseline age was 43 months (range 8-227). Most UCB infusions were allogeneic (80%), and 10/11 studies applied UCB intravenously. The median pre-thaw dose of intravenous-infused UCB was 46.7x10^6 total nucleated cells/kg (range 7.7-210.3). The pooled effect at 6 months post-intravenous UCB was an average change from baseline GMFM-66 of 0.93 (95% CI: 0.12, 1.75; p=0.027) points greater among UCB-treated participants (+/- EPO) compared to controls. There was also a statistically significant positive pooled cell dose effect at 6 months post-intervention (p=0.005), indicating that higher cell doses were associated with greater GMFM-66 increases. There was negligible between-study heterogeneity in both the treatment effect and the cell dose effect at 6 months. Discussion UCB improves gross motor function, and higher dose is beneficial. Future exploration of additional timepoints in addition to co-variates including age at infusion, severity, and etiology is underway and may elucidate responder subgroups and reveal increased efficacy.