{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:41:17Z","timestamp":1777977677971,"version":"3.51.4"},"reference-count":24,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council, Lions Cord Blood Foundation, Monash Health Foundation"},{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lions Cord Blood Foundation"},{"DOI":"10.13039\/501100001232","name":"Royal Australasian College of Physicians","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001232","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australia\u2019s National Health and Medical Research Council"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,6,5]]},"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Severe intraventricular haemorrhage (IVH) and white matter injury (WMI) are major neurological complications in preterm infants, leading to long-term neurodevelopmental impairments. Despite advances in neonatal care, effective treatments are lacking. Umbilical cord blood cell (UCBC) therapy shows neuroprotective potential, with autologous sources ideal but often not feasible due to the unpredictability of preterm births. Allogeneic UCBCs offer an alternative, although immunogenicity and human leucocyte antigen (HLA) compatibility present challenges with knowledge gaps in their relevance in neonatal populations. This study aims to assess the feasibility and safety of partially HLA-matched allogeneic UCBC therapy in preterm infants with severe brain injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The ALLO trial is an open-label, phase I, single-arm feasibility and safety study conducted at Monash Children\u2019s Hospital, Victoria, Australia. Preterm infants born before 28 weeks (ALLO-1) or between 28 weeks and 36+6 weeks (ALLO-2) gestational age with severe brain injury identified on neuroimaging will be enrolled. Severe brain injury is defined as grade 3 or 4 IVH or significant WMI. Exclusion criteria include major congenital anomalies or redirection to comfort care. Eligible infants will receive a single intravenous infusion of unrelated, allogeneic, partially HLA-matched (4\/6 or 5\/6 HLA match) UCBCs sourced from a public cord blood bank. The target dose is 50\u2009million total nucleated cells per kilogram body weight. Infusion will occur within 2\u20133\u2009weeks of confirmation of eligibility, contingent on clinical stability and absence of active sepsis. Primary outcome includes: (1) feasibility, defined as having more than 60% of enrolled infants with an eligible allogeneic partially matched cord blood unit available and (2) safety, defined as absence of severe adverse events within 48 hours of infusion or graft-versus-host disease within 3\u2009months of infusion. Secondary outcomes include survival, neonatal morbidities, neurodevelopmental assessments and serum cytokine analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>Monash HREC has granted full ethics approval (RES-23-0000-297A) for the study, including the research use of allogeneic cord blood from compassionate donations by healthy donors, facilitated through the Bone Marrow Donor Institute Cord Blood Bank within the AusCord network. Findings will be disseminated through peer-reviewed publications and conference presentations, contributing to the development of novel neuroreparative therapies for preterm brain injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>ACTRN12623001352695 (The Australian New Zealand Clinical Trials Registry).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-100389","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T05:31:40Z","timestamp":1750224700000},"page":"e100389","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Safety and feasibility of allogeneic cord blood-derived cell therapy in preterm infants with severe brain injury (ALLO trial): a phase-1 trial protocol"],"prefix":"10.1136","volume":"15","author":[{"given":"Abdul","family":"Razak","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Monash University, Melbourne, Victoria, Australia"},{"name":"Monash Newborn, Monash Children\u2019s Hospital, Melbourne, Victoria, Australia"},{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristyn","family":"Connelly","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Melbourne, Victoria, Australia"},{"name":"Monash Newborn, Monash Children\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-1739","authenticated-orcid":false,"given":"Rod W","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Melbourne, Victoria, Australia"},{"name":"Cerebral Palsy Alliance Research Institute, Cerebral Palsy Alliance, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne L","family":"Miller","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney A","family":"McDonald","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Jenkin","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Melbourne, Victoria, Australia"},{"name":"Monash Newborn, Monash Children\u2019s Hospital, Melbourne, Victoria, Australia"},{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison CB","family":"Paton","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Melbourne, Victoria, Australia"},{"name":"Cerebral Palsy Alliance Research Institute, Cerebral Palsy Alliance, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology-Oncology, Monash Children\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, The Royal Children's Hospital, Melbourne, Victoria, Australia"},{"name":"BMDI Cord Blood Bank, The Royal Children's Hospital, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathie","family":"Hart","sequence":"additional","affiliation":[{"name":"Australian Red Cross Lifeblood, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ngaire J","family":"Elwood","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, The Royal Children's Hospital, Melbourne, Victoria, Australia"},{"name":"BMDI Cord Blood Bank, The Royal Children's Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-4182","authenticated-orcid":false,"given":"Atul","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Melbourne, Victoria, Australia"},{"name":"Monash Newborn, Monash Children\u2019s Hospital, Melbourne, Victoria, Australia"},{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"2025071022162725000_15.6.e100389.1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.7473","article-title":"Interventions to Reduce Severe Brain Injury Risk in Preterm Neonates: A Systematic Review and Meta-analysis","volume":"6","author":"Razak","year":"2023","journal-title":"JAMA Netw Open"},{"key":"2025071022162725000_15.6.e100389.2","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1159\/000537801","article-title":"Temporal Trends in Severe Brain Injury and Associated Outcomes in Very Preterm Infants","volume":"121","author":"Razak","year":"2024","journal-title":"Neonatology"},{"key":"2025071022162725000_15.6.e100389.3","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2018-316664"},{"key":"2025071022162725000_15.6.e100389.4","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2017.00200","article-title":"Perinatal Brain Injury As a Consequence of Preterm Birth and Intrauterine Inflammation: Designing Targeted Stem Cell Therapies","volume":"11","author":"Paton","year":"2017","journal-title":"Front Neurosci"},{"key":"2025071022162725000_15.6.e100389.5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/pr.2017.236","article-title":"Umbilical cord blood cells for treatment of cerebral palsy; timing and treatment options","volume":"83","author":"McDonald","year":"2018","journal-title":"Pediatr Res"},{"key":"2025071022162725000_15.6.e100389.6","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-018-1089-5","article-title":"Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following perinatal hypoxic-ischemic brain injury","volume":"15","author":"McDonald","year":"2018","journal-title":"J Neuroinflammation"},{"key":"2025071022162725000_15.6.e100389.7","doi-asserted-by":"crossref","first-page":"147001","DOI":"10.1016\/j.brainres.2020.147001","article-title":"Multiple doses of umbilical cord blood cells improve long-term brain injury in the neonatal rat","volume":"1746","author":"Penny","year":"2020","journal-title":"Brain Res"},{"key":"2025071022162725000_15.6.e100389.8","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/stcltm\/szad048","article-title":"Allogeneic Cell Therapy Applications in Neonates: A Systematic Review","volume":"12","author":"Razak","year":"2023","journal-title":"Stem Cells Transl Med"},{"key":"2025071022162725000_15.6.e100389.9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/stcltm\/szab024","article-title":"Umbilical Cord Blood and Cord Tissue-Derived Cell Therapies for Neonatal Morbidities: Current Status and Future Challenges","volume":"11","author":"Zhou","year":"2022","journal-title":"Stem Cells Transl Med"},{"key":"2025071022162725000_15.6.e100389.10","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.3390\/ijms24054351","article-title":"Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury: A Systematic Review & Meta-Analysis of Preclinical Studies","volume":"24","author":"Nguyen","year":"2023","journal-title":"IJMS"},{"key":"2025071022162725000_15.6.e100389.11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/stcltm\/szad006","article-title":"Factors Influencing the Efficacy of Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury","volume":"12","author":"Purcell","year":"2023","journal-title":"Stem Cells Transl Med"},{"key":"2025071022162725000_15.6.e100389.12","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jcyt.2023.01.001","article-title":"Feasibility of cord blood collection for autologous cell therapy applications in extremely preterm infants","volume":"25","author":"Zhou","year":"2023","journal-title":"Cytotherapy"},{"key":"2025071022162725000_15.6.e100389.13","doi-asserted-by":"crossref","first-page":"105492","DOI":"10.1016\/j.ebiom.2024.105492","article-title":"Feasibility and safety of autologous cord blood derived cell administration in extremely preterm infants: a single-centre, open-label, single-arm, phase I trial (CORD-SaFe study)","volume":"111","author":"Zhou","year":"2025","journal-title":"EBioMedicine"},{"key":"2025071022162725000_15.6.e100389.14","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jcyt.2021.07.001","article-title":"Safety of allogeneic umbilical cord blood infusions for the treatment of neurological conditions: a systematic review of clinical studies","volume":"24","author":"Paton","year":"2022","journal-title":"Cytotherapy"},{"key":"2025071022162725000_15.6.e100389.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(78)80282-0"},{"key":"2025071022162725000_15.6.e100389.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(05)80189-5"},{"key":"2025071022162725000_15.6.e100389.17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.expneurol.2016.06.017","article-title":"Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells","volume":"283","author":"Li","year":"2016","journal-title":"Exp Neurol"},{"key":"2025071022162725000_15.6.e100389.18","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/sctm.17-0219","article-title":"Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial","volume":"7","author":"Ahn","year":"2018","journal-title":"Stem Cells Transl Med"},{"key":"2025071022162725000_15.6.e100389.19","first-page":"344","article-title":"A New Hope in the Treatment of Intraventricular Haemorrhage in Preterm Infants: Mesenchymal Stem Cells","volume":"32","author":"Bozkaya","year":"2022","journal-title":"Turk Neurosurg"},{"key":"2025071022162725000_15.6.e100389.20","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.13550","article-title":"Early Neurodevelopmental Assessments for Predicting Long-Term Outcomes in Infants at High Risk of Cerebral Palsy","volume":"7","author":"Razak","year":"2024","journal-title":"JAMA Netw Open"},{"key":"2025071022162725000_15.6.e100389.21","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/jpc.16654","article-title":"Early neurodevelopmental outcomes of preterm infants with intraventricular haemorrhage and periventricular leukomalacia","volume":"60","author":"Ng","year":"2024","journal-title":"J Paediatr Child Health"},{"key":"2025071022162725000_15.6.e100389.22","doi-asserted-by":"crossref","DOI":"10.1186\/s40814-021-00770-x","article-title":"Determining sample size for progression criteria for pragmatic pilot RCTs: the hypothesis test strikes back!","volume":"7","author":"Lewis","year":"2021","journal-title":"Pilot Feasibility Stud"},{"key":"2025071022162725000_15.6.e100389.23","unstructured":"National Health and Medical Research Council . Guidance: safety monitoring and reporting in clinical trials involving therapeutic goods. 2016. Available: https:\/\/www.nhmrc.gov.au\/guidelines-publications\/eh59 [Accessed 13 Mar 2023]."},{"key":"2025071022162725000_15.6.e100389.24","unstructured":"National Health and Medical Research Council . National statement on ethical conduct in human research. 2007. Available: https:\/\/www.nhmrc.gov.au\/about-us\/publications\/national-statement-ethical-conduct-human-research-2007-updated-2018#block-views-block-file-attachments-content-block-1 [Accessed 13 Mar 2023]."}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-100389","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T05:18:04Z","timestamp":1752211084000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-100389"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,18]]},"published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1136\/bmjopen-2025-100389"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-100389","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]}}}