Two-year outcomes of infants enrolled in the first-in-human study of amnion cells for bronchopulmonary dysplasia

Abstract

We previously reported on the immediate safety and neonatal outcomes of six premature infants with severe bronchopulmonary dysplasia (BPD) who were administered human amnion epithelial cells (hAECs). One infant died in the neonatal period due to unrelated causes. In this study, we aimed to assess the long‐term safety and follow‐up outcomes of the five surviving infants until 2 years corrected age (CA). hAECs were administered intravenously at a dose of 1 × 106 cells per kilogram after 36 weeks postconceptional age in infants with established BPD. Study follow‐up consisted of assessment of any adverse events, growth, and respiratory, cardiac, and neurodevelopmental outcomes over four time points (6, 12, 18, and 24 months CA). Investigations included chest x‐rays, cranial and abdominal ultrasounds, and echocardiograms at regular intervals as well as a magnetic resonance imaging (MRI) brain at 2 years CA. All five infants were alive at 2 years CA. Median time to wean off oxygen was 24 (10‐36) months. Two infants had pulmonary hypertension, which resolved by 2 years of age. Four infants were rehospitalized briefly for viral or bacterial infections during the 2 years. MRI brain findings included normal (n = 1), and mild to moderate white matter loss (n = 2). Neurodisabilities diagnosed included hemiplegic cerebral palsy (n = 1), global developmental delay (n = 3), and severe hearing loss (n = 3). No evidence of tumor formation was noted on physical examinations or on any imaging. There were no long‐term adverse events observed that could be attributed to hAEC administration. We observed long‐term effects of extreme prematurity and severe BPD in the cohort.

Allogeneic administration of human umbilical cord-derived mesenchymal stem/stromal cells for bronchopulmonary dysplasia: preliminary outcomes in four Vietnamese infants

“…A previous study reported the safety outcomes of the allogeneic administration of human UCB-MSCs, in which nine preterm infants received either a single dose of 1 × 10 7 cells/kg or 2 × 10 7 cells/kg [23]. In another single-center, open-label phase 1 trial, Lim's group administered 1 × 10 6 human amnion epithelial cells to six preterm infants with established BPD and reported the safety profile at 2 years postadministration [24,25]. In these trials, as in ours, no infusion toxicity or allogeneic UC-MSC intervention-associated adverse events were recorded.…”

Allogeneic Administration of Human Umbilical Cord-derived Mesenchymal Stem/Stromal Cells for Bronchopulmonary Dysplasia: Preliminary Outcomes in Four Vietnamese Infants.

“…A previous study reported the safety outcomes of the allogeneic administration of human UCB-MSCs, in which nine preterm infants received either a single dose of 1x10 7 cells/kg or 2x10 7 cells/kg (22). In another single-center, open-label phase 1 trial, Lim's group administered 1x10 6 human amnion epithelial cells to six preterm infants with BPD and reported the safety pro le at 2 years postadministration (23,24). In these trials, as in ours, no infusion toxicity or allogeneic UC-MSC intervention-associated AEs were recorded.…”

Allogeneic Administration of Human Umbilical Cord-derived Mesenchymal Stem/Stromal Cells for Bronchopulmonary Dysplasia: Preliminary Outcomes in Four Vietnamese Infants.

“…A previous study reported the safety outcomes of the allogeneic administration of human UCB-MSCs, in which nine preterm infants received either a single dose of 1x10 7 cells/kg or 2x10 7 cells/kg (23). In another single-center, open-label phase 1 trial, Lim's group administered 1x10 6 human amnion epithelial cells to six preterm infants with established BPD and reported the safety pro le at 2 years postadministration (24,25). In these trials, as in ours, no infusion toxicity or allogeneic UC-MSC intervention-associated adverse events were recorded.…”