{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T18:43:37Z","timestamp":1786214617918,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Amustaline (S\u2010303)\/glutathione (GSH) pathogen\u2010reduced red blood cells (PR\u2010RBCs) are in development for all adult and pediatric RBC transfusion indications, including neonates and infants. A neonatal rat model evaluated the safety and tolerability of PR\u2010RBCs during growth and maturation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design and Methods<\/jats:title>\n                    <jats:p>Repeated transfusions of 10\u2009mL\/kg syngeneic untreated (control) RBCs, PR\u2010treated (study) or \u201chigh\u2010degradant\u201d PR\u2010RBCs were transfused three\u2010times weekly to neonatal Sprague\u2013Dawley rats from post\u2010natal day (PND) 4 through adolescence (PND 64). The high\u2010degradant PR\u2010RBCs utilized amustaline concentrations 5\u2010fold higher than in the clinical process, without a terminal wash step. Toxicokinetic characteristics of the major amustaline degradant (S\u2010300) were determined on PNDs 15, 29 and at study termination. Animal well\u2010being, weight, sexual maturation, and cognitive development (using the Morris water maze) were monitored. On PND 65\u201368 terminal necropsy and pathological analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All recipient groups demonstrated normal and comparable weight gain, sexual maturation, and cognitive development. There were no PR\u2010RBC\u2010related effects on clinical signs, clinical chemistry, gross\u2010 or histopathology, although all rats had polycythemia (Hb 16.6\u201317.0\u2009g\/dL) with reduced reticulocytes (0.6\u20131.4%) at study end. S\u2010300 was cleared rapidly (&lt;60\u2009min in the study group) and did not accumulate in the blood. The high\u2010degradant PR\u2010RBC group, with 6.2\u2010fold reduced species\u2010specific scaling for increased basal metabolic rate, were exposed to ~11.8\u2010fold higher S\u2010300 exposure than expected in repeatedly\u2010transfused patients, without apparent adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The neonatal rat study demonstrates the safety and tolerability of amustaline\/GSH PR\u2010RBCs for transfusion and supports clinical use in pediatric patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.70240","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T05:39:31Z","timestamp":1777095571000},"page":"1603-1612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and tolerability of amustaline\/glutathione pathogen\u2010reduced red blood cells in neonatal rats"],"prefix":"10.1111","volume":"66","author":[{"given":"Anne","family":"North","sequence":"first","affiliation":[{"name":"Cerus Corporation  Concord California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Corash","sequence":"additional","affiliation":[{"name":"Cerus Corporation  Concord California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-4744","authenticated-orcid":false,"given":"Richard J.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Cerus Corporation  Concord California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Mufti","sequence":"additional","affiliation":[{"name":"Cerus Corporation  Concord California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpediatrics.2010.269"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2016.06.005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2020.102951"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2014.1360"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03132.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15662"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.17854"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000324458"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2006.00959.x"},{"key":"e_1_2_10_11_1","unstructured":"Guideline on the need for non\u2010clinical testing in juvenile animals of pharmaceuticals for paediatric indications. Committee for medicinal products for human use (CHMP).European Medicines Agency Evaluation of Medicines for Human Use EMEA.2008."},{"key":"e_1_2_10_12_1","volume-title":"Guide for the care and use of laboratory animals guide for the care and use of laboratory animals","author":"National Research Council","year":"2011"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2009.10.019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0023-9690(81)90020-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0892-0362(91)90066-6"},{"key":"e_1_2_10_16_1","first-page":"1431","article-title":"The laboratory rat: age and body weight matter","volume":"20","author":"Ghasemi A","year":"2021","journal-title":"EXCLI J"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1293\/tox.26.29"},{"key":"e_1_2_10_18_1","first-page":"144","article-title":"Changes in blood parameters and the expression of coagulation\u2010related genes in lactating Sprague\u2013Dawley rats","volume":"51","author":"Urasoko Y","year":"2012","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1258\/la.2010.009049"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.18117"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000005716"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15965"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2020.09.001"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15963"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V13.8.789.789"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2025.103426"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.70240","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/trf.70240","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.70240","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T18:29:45Z","timestamp":1786213785000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.70240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/trf.70240"],"URL":"https:\/\/doi.org\/10.1111\/trf.70240","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"2025-12-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}