Adequately Dosed Autologous Cord Blood Infusion is Associated with Motor Improvement in Children with Cerebral Palsy

Cerebral palsy (CP) is caused by injury to the developing brain, often via stroke, hypoxia or hemorrhage. Current treatments are supportive only. Umbilical cord blood (CB) prevents neurologic damage in children withleukodystrophies and improves motor function in animal models of brain injury and CP. We conducted a randomized trial to assess the efficacy of autologous CB infusion in young children with CP. The Cerebral Palsy-Autologous Cord Blood study is a prospective, randomized, double blind, placebo controlled crossover study of a single IV infusion of autologous CB in children ages 1-6 years with CP. Motor function is classified by Gross Motor Classification System (GMFCS) level. Eligible children were (1) GMFCS level 2-4 or (2) GMFCS level 1 with hemiplegia if the affected hand was used as an assist only. Children with known genetic conditions, intractable seizures or severe microcephaly were excluded. Autologous CB units had to have a pre-cyropreservation total nucleated cell count (TNCC) ≥1x107/kg, negative sterility culture and maternal infectious disease screening, and HLA confirmation. Subjects were randomized to the order of CB and placebo infusions (given one year apart). CB units, shipped to and stored at Duke cryopreserved, were thawed and washed on the day of infusion. Infusions, dosed at 1-5x107/kg based on pre-cryopreservation TNCC, were given IV over 5-10 minutes in the clinic after premedication with Tylenol, Benadryl and Solumedrol. Subjects received IV fluids and were monitored for 2-4 hours post-infusion. Functional assessments and brain MRI were performed at baseline, one and two years. The primary endpoint was change in Gross Motor Function Measure-66 (GMFM-66) score one year after initial infusion. Sixty-three children were enrolled with a median baseline age of 2 years (range 1– 6). Median TNCC of CB infusion was 2x107/kg (range 0.4–5), median CD34 dose 0.5x105/kg (range 0.05–4). Despite negative pre-cryopreservation cultures, one unit grew β-hemolytic strep upon thaw. There were no clinical infections. There was no difference in GMFM-66 change scores between placebo and treated groups as a whole (6.9 vs. 7.5, p=0.72). However, treated subjects who received pre-cryopreservation cell doses ≥2.5x107/kg showed statistically significant improvement in GMFM-66 change scores compared to subjects who received lower doses (p<0.01). A similar result was observed using the median infused dose of 1.98x107/kg (p=0.05). Infused dose was not related to CP type (p=0.32) or severity (p=0.46). When adequately dosed, CB may improve motor function in young children with CP. We observed improvement at pre-cryopreservation cell doses (≥2.5x107/kg) that correspond with the minimum cell dose used for hematopoietic reconstitution in patients undergoing allogeneic CB transplantation.