Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi-do, Republic of Korea.
Rehabilitation and Regeneration Research Center, CHA University, Seongnam, Republic of Korea.
Stem Cell Res Ther. 2020 Nov 27;11(1):509. doi: 10.1186/s13287-020-02020-y.
Concomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP.
Children diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 10/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored.
Eighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration.
These results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects.
ClinicalTrials.gov, NCT01991145 , registered 25 November 2013.
在脑瘫（CP）患儿中，异体脐血（UCB）输注和促红细胞生成素（EPO）联合治疗显示出治疗效果。然而，尚无临床研究采用 2×2 四因素析因盲法设计的 4 个组来研究 UCB 和 EPO 联合治疗的效果。本随机安慰剂对照试验旨在确定 UCB 细胞和 EPO 联合治疗 CP 的协同作用和单独疗效。
将确诊为 CP 的患儿随机分为 4 组：（A）UCB+EPO，（B）UCB+安慰剂 EPO，（C）安慰剂 UCB+EPO，（D）安慰剂 UCB+安慰剂 EPO。根据 UCB 单位选择标准，要求 HLA-A、-B 和-DRB1 匹配≥4/6，总核细胞（TNC）数≥3×10/kg，对患儿进行静脉内输注异基因 UCB，并给予 500IU/kg 人重组 EPO 治疗 6 次。从基线到治疗后 12 个月，进行功能测量、脑成像研究和脑电图检查。此外，还密切监测不良反应事件。
92 例患儿中 88 例（3.05±1.22 岁）完成了研究。与治疗后 1 个月（△2.30 对△0.71，P=0.025）和 12 个月（△6.85 对△2.34，P=0.018）相比，A 组的总体运动表现测量（GMPM）改善更大。调整基线运动功能后，计算 GMPM 变化率。与 D 组相比，A 组在治疗后 1 个月和 12 个月时 GMPM 变化率的改善更大。治疗后 12 个月时，GMPM 变化率的顺序为 A、B、C 和 D。这些结果表明 UCB 和 EPO 联合治疗的协同作用优于单一治疗。在弥散张量成像中，年龄≥3 岁亚组中，体感辐射的各向异性分数变化比率在 A 组高于 D 组。此外，A 组中较高的 TNC 和更多 HLA 匹配的 UCB 单位导致更好的总体运动结果。UCB 或 EPO 给药后，不良反应保持不变。
这些结果表明，EPO 可增强异体 UCB 细胞对 CP 患儿神经恢复的疗效，且无不良影响。
ClinicalTrials.gov，NCT01991145，2013 年 11 月 25 日注册。
