336 - Allogeneic Cord Blood Stem Cells Transplantation for Intraventricular Hemorrhage in Preterm Infants: A Double blinded Randomized Placebo Controlled Phase 2 Trial

Publication Number: 336.4025

So Yoon Ahn, Samsung Medical Center, Seoul, Seoul-t'ukpyolsi, Republic of Korea; Misun Yang, Samsung Medical Center, Gangnam, Seoul-t'ukpyolsi, Republic of Korea; Yun Sil Chang, Samsung Medical Center, Gangnam gu, Seoul-t'ukpyolsi, Republic of Korea

Background: We previously conducted a Phase 1 clinical trial of mesenchymal stem cells (MSC) transplantation for severe intraventricular hemorrhage (IVH) in premature infants, demonstrating its safety and feasibility. As the next step, we performed a double-blind, randomized controlled Phase 2 clinical trial to evaluate the efficacy of MSC for IVH.

Objective: We aimed to prove the therapeutic efficacy of MSC in attenuating IVH induced complications in premature infants.

Design/Methods: A Phase 2 double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants diagnosed with severe IVH (Papile Grade 3 or 4). Allogeneic umbilical cord blood-MSCs (1×10^7 cells/kg) or an equivalent volume of normal saline were administered intracerebroventricularly within 7 days of the severe IVH diagnosis. The primary outcome was the rate of need for shunt surgery or death. Secondary outcomes included neurological complications, such as severe delay measured by Bayley-III and the Korean Developmental Screening Test (KDST), cerebral palsy (CP) defined by a Gross Motor Function Classification System score (GMFCS) of ≥1, and newly onset seizures. Additionally, neurological complications were analyzed by subgroup based on periventricular hemorrhagic infarction (PVHI) scores.

Results: The gestational age and birth weight of infants were 24.8±1.8 weeks and 757±184 grams in the control group (n=11) and 26.0±2.6 weeks and 878±288 grams in the MSC group (n=11), without differences between the groups. All infants showed Grade 4 IVH on brain ultrasound at the screening. In the control group, 2 infants died, and 5 required shunt placement, while in the MSC group, 3 infants died, and 5 underwent shunt placement. The incidence of death or shunt did not differ between groups (control vs. MSC, 64% vs. 73%). At the two-year follow-up, the rate of CP defined by a GMFCS level of ≥1, was significantly lower in the MSC (50%, 4/8) compared to the control (89%, 8/9). In a subgroup analysis based on the severity of PVHI observed in the screening ultrasound, infants with severe PVHI in the MSC group exhibited a lower incidence of severe delays in cognitive function (control vs. MSC, 100% vs. 17%) and adaptive behavior function (control vs. MSC, 100% vs. 50%) as measured by the Bayley-III assessment, when compared to control group with severe PVHI.

Conclusion(s): In premature infants with severe IVH, MSC transplantation didn't reduce the rate of death or shunt operation. However, our findings suggest a potential therapeutic benefit of MSCs for mitigating neurological complications associated with severe IVH in premature infants.