Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy.

Abstract

Objective

To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE).

Study design

We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells.

Results

Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85.

Conclusions

Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.jpeds.2013.11.036

Publication Info

Cotten, C Michael, Amy P Murtha, Ronald N Goldberg, Chad A Grotegut, P Brian Smith, Ricki F Goldstein, Kimberley A Fisher, Kathryn E Gustafson, et al. (2014). Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. The Journal of pediatrics, 164(5). pp. 973–979.e1. 10.1016/j.jpeds.2013.11.036 Retrieved from https://hdl.handle.net/10161/24697.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Cotten

Charles Michael Cotten

Professor of Pediatrics

I am involved in 4 major areas of research:
1) Neuroprotection. Working with colleagues from Cell Therapies, we have added to Duke's experience participating in pivotal trials of hypothermia for term newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE) by completing a phase I study of autologous cord blood cells for these infants, and developing and currently leading a multicenter, double-blind randomized clinical trial of autologous cord blood cells or placebo in term infants with moderate or severe HIE. We recently completed, w/ funding from Duke's CTSI support, the first phase I single center study of allogeneic cord tissue derived mesenchymal stromal cells for newborns with moderate or severe HIE who do not have autologous cells available.
2) Genomics. We at Duke have been in the NICHD Neonatal Research Network (NRN) since 2001. I led the NRN's development of an Anonymized DNA bank of samples collected from 1,000 extremely low birthweight infants, with phenotype information linked to the samples. This resource has been the basis for multiple candidate gene, and genome wide scan analysis, and has identified variants associated with severe retinopathy of prematurity and necrotizing enterocolitis. We are in the process of partnering with the Vermont Oxford Network-Rady Genomics collaborative to bring 48 hour turnaround Whole Genome Sequencing to patients in the Duke Intensive Care Nursery. 
3) New Technologies: I have collaborated with Drs. David Millington from Duke and Vamsee Pamula (a Duke Pratt School graduate), from BAEBIES Inc, on prototype new technology devices for use in newborn screening for lysosomal storage disease as well as multiplex chips for screening for hyperbilirubinemia and related conditions, as well as working with Dr. Pamula and Dr. Michael Freemark (Peds Endocrinology) on screening panels for hypoglycemia and hypothyroidism, and with investigators from UAB on an Acute Kidney Injury panel. Also, I am collaborating with Dr. Cynthia Toth in pediatric ophthalmology, and Pratt School investigators to develop and apply use of optical coherence tomography for retinal imaging that will assess associations between retinal neurovascular development, brain development, and neurodevelopmental outcomes. I recently worked with the Duke FORGE and multiple Pediatric subspecialists on machine-learning and deep informatics analysis of electronic health records to quantify risk for subsequent complications and on development of algorithms to identify neonatal seizures from neonatal EEG tracings. 
4)Microbiome in Micropreemies and health outcomes of periviable infants.  I have worked with multiple epidemiology researchers to assess practice variation within our center, and within the Neonatal Research Network centers, to identify how variation in practice can influence outcomes, with a particular focus on antibiotic use. This work demonstrated strong associations between high empirical antibiotic use in infants with sterile cultures and subsequent morbidities and mortality. This discovery has led to strong collaborations and new initiatives by young faculty leading studies of the evolving microbiome, leading to hypothesis generation re: the microbiome and optimal growth in extremely preterm infants.

Goldberg

Ronald Norman Goldberg

Dorothy J. Shaad/Angus M. McBryde, Sr. Distinguished Professor Emeritus

1. Perinatal asphyxia and neuroprotection - use of umbilical cord blood transfusion
2. Persistent Pulmonary hypertension - use of ethyl nitrite
3. The extremely low-birth-weight infant.
4. Newborn screening - use of digital microfluidics

Gustafson

Kathryn E. Gustafson

Professor in Psychiatry and Behavioral Sciences

My scholarly interests and expertise are in pediatric neurodevelopmental outcomes assessment and research as well as child and parent coping with chronic childhood illness. I collaborated with Dr. Robert Thompson on a research program investigating the transactional biopsychosocial model of adaptation to pediatric conditions in children and families. Our research program was funded by the NIH and culminated in the publication of our book, Adaptation to Chronic Childhood Illness. In addition, because of my expertise in neurodevelopmental functioning, I collaborate with the Division of Neonatology and the Duke Neonatal-Perinatal Research Unit on neurodevelopmental outcomes research with high-risk infants, toddlers, and school-age children. I am a gold standard psychology consultant to the Neonatal Research Network (NRN) of the NIH/NICHD, train and certify psychologists around the country in infant and toddler developmental assessment, and serve as consultant for protocol development.  In addition, I collaborate with colleagues in Pediatric Ophthalmology to investigate preterm optic nerve anatomy assessed via optical coherence tomography imaging and the association with neurodevelopment. I am also involved in investigations of umbilical cord blood stem cell transplant for young children with hypoxic ischemic encephalopathy, cerebral palsy, and inborn errors of metabolism with colleagues in the Blood and Marrow Transplantation program.

Swamy

Geeta Krishna Swamy

Haywood Brown, MD Distinguished Professor of Women's Health

Dr. Geeta Swamy, MD, is Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, having served as the director of the Duke Perinatal Research Center and Vice Chair for Research and Faculty Development in the Department of ObGyn. She has achieved international acclaim as a clinician researcher and expert in the field of maternal immunization and perinatal infection. As a consultant to the World Health Organization, Dr. Swamy contributes her knowledge to advance international work to evaluate the immunogenicity, safety, and efficacy of vaccines in pregnant women. The American College of ObGyn has grown to be the “collective voice” for women’s health, and Dr. Swamy has been a leader within that organization for the last two decades. She currently serves as the Co-Principal Investigator for the NIH-NIAID Vaccine Treatment and Evaluation (VTEU) and CDC Clinical Immunization Safety Assessment. In addition, she has been a leader at Duke and nationally in promoting a culture of scientific integrity and transparency in research. She has been instrumental in developing and leading the School of Medicine’s research initiatives in administration, regulatory oversight, and compliance. In 2018, she became Vice Dean for Scientific Integrity in the School of Medicine and Associate Vice President for Research for Duke University. In these roles she oversees the Duke Office of Scientific Integrity (DOSI) which houses the Advancing Scientific Integrity, Services, & Training (ASIST) initiative, conflict of interest, clinical quality management, incident response in research, and research misconduct. She also oversees the Duke Office of Research Initiatives, the Duke Health IRB, Office of Research Administration (ORA), and Office of Research Contracts (ORC). 




Kurtzberg

Joanne Kurtzberg

Jerome S. Harris Distinguished Professor of Pediatrics

Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood and birthing tissues in the emerging fields of cellular therapies and regenerative medicine.   Dr. Kurtzberg serves as the Director of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant and Cellular Therapy Program, Director of the Carolinas Cord Blood Bank, and Co-Director of the Stem Cell Transplant Laboratory at Duke University.  The Carolinas Cord Blood Bank is an FDA licensed public cord blood bank distributing unrelated cord blood units for donors for hematopoietic stem cell transplantation (HSCT) through the CW Bill Young Cell Transplantation Program.  The Robertson GMP Cell Manufacturing Laboratory supports manufacturing of RETHYMIC (BLA, Enzyvant, 2021), allogeneic cord tissue derived and bone marrow derived mesenchymal stromal cells (MSCs), and DUOC, a microglial/macrophage cell derived from cord blood.

Dr. Kurtzberg’s research in MC3 focuses on translational studies from bench to bedside, seeking to develop transformative clinical therapies using cells, tissues, molecules, genes, and biomaterials to treat diseases and injuries that currently lack effective treatments. Recent areas of investigation in MC3 include clinical trials investigating the safety and efficacy of autologous and allogeneic cord blood in children with neonatal brain injury – hypoxic ischemic encephalopathy (HIE), cerebral palsy (CP), and autism. Clinical trials testing allogeneic cord blood are also being conducted in adults with acute ischemic stroke. Clinical trials optimizing manufacturing and testing the safety and efficacy of cord tissue MSCs in children with autism, CP and HIE and adults with COVID-lung disease are underway. DUOC, given intrathecally, is under study in children with leukodystrophies and adults with primary progressive multiple sclerosis.

In the past, Dr. Kurtzberg has developed novel chemotherapeutic drugs for acute leukemias, assays enumerating ALDH bright cells to predict cord blood unit potency, methods of cord blood expansion, potency assays for targeted cell and tissue based therapies. Dr. Kurtzberg currently holds several INDs for investigational clinical trials from the FDA.  She has also trained numerous medical students, residents, clinical and post-doctoral fellows over the course of her career.


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