Motor function and safety after allogeneic cord blood and cord tissue‐derived mesenchymal stromal cells in cerebral palsy: An open‐label, randomized trial

Abstract Aim To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue‐derived mesenchymal stromal cells (hCT‐MSC) in children with cerebral palsy (CP). Method Ninety‐one children (52 males, 39 females; median age 3 years 7 months [range 2–5 years]) with CP due to hypoxic–ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 × 10 7 AlloCB total nucleated cells (TNC) per kilogram at baseline ( n = 31); (2) the hCT‐MSC group received 2 × 10 6 hCT‐MSC at baseline, 3 months, and 6 months ( n = 28); (3) the natural history control group received 10 × 10 7 AlloCB TNC per kilogram at 12 months ( n = 31). Motor function was assessed with the Gross Motor Function Measure‐66 (GMFM‐66) and Peabody Developmental Motor Scale, Second Edition. Results Infusions ( n = 143) were well tolerated, with eight infusion reactions (three in the AlloCB group, five in hCT‐MSC) and no other safety concerns. At 12 months, the mean differences (95% confidence intervals [CI]) between actual and expected changes in GMFM‐66 score were AlloCB 5.8 points (3.4–8.2), hCT‐MSC 4.3 (2.2–6.4), and natural history 3.1 (1.4–5.0). In exploratory, post hoc analysis, the mean GMFM‐66 score (95% CI) of the hCT‐MSC group was 1.4 points higher than natural history (−1.1 to 4.0; p = 0.27), and the AlloCB group was 3.3 points higher than natural history (0.59–5.93; p = 0.02) after adjustment for baseline Gross Motor Function Classification System level, GMFM‐66 score, and etiology. Interpretation High‐dose AlloCB is a potential cell therapy for CP and should be further tested in a randomized, blinded, placebo‐controlled trial. What this paper adds Unrelated donor allogeneic umbilical cord blood (AlloCB) and human umbilical cord tissue‐derived mesenchymal stromal cell infusion is safe in young children with cerebral palsy. Significant changes in motor function were not observed 6 months after treatment. One year later, treatment with AlloCB was associated with greater increases in Gross Motor Function Measure‐66 scores.