{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:09:37Z","timestamp":1792796977405,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background\/Objectives<\/jats:title>\n                    <jats:p>Outcomes for pediatric relapsed\/refractory (R\/R) acute myeloid leukemia (AML) remain dismal. CPX\u2010351, a liposomal formulation of cytarabine and daunorubicin, may have less off\u2010target toxicities than traditional chemotherapies and has shown improved outcomes for adults with newly diagnosed therapy\u2010related AML.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design\/Methods<\/jats:title>\n                    <jats:p>\n                      In this first\u2010in\u2010pediatric, single center phase 1 study (NCT01943682), 27 patients with R\/R acute leukemia (acute lymphoblastic leukemia [ALL,\n                      <jats:italic>n<\/jats:italic>\n                      = 3], AML [\n                      <jats:italic>n<\/jats:italic>\n                      = 23], or mixed phenotype acute leukemia [MPAL,\n                      <jats:italic>n<\/jats:italic>\n                      = 1]) received one cycle of CPX\u2010351 (on days 1, 3, 5) at either 44\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      daunorubicin\/dose or 59\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      daunorubicin\/dose. The primary objectives were to determine the CPX\u2010351 recommended phase 2 dose (RP2D) and to evaluate its tolerability; secondary objectives were to assess marrow overall response rate (ORR) and cardiotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The RP2D was determined to be 44\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      daunorubicin\/dose. Grade \u22653 non\u2010hematologic toxicities occurred in 89% of patients including febrile neutropenia (85%), infection (52%), and maculo\u2010papular rash (37%). No grade \u22653 acute cardiac toxicities or significant changes in cardiac biomarkers were detected. The marrow ORR for AML patients was 48% (10\/21 evaluable patients), despite high\u2010risk genetic findings in most and nearly half of patients having undergone prior hematopoietic stem cell transplant. No patients with ALL or MPAL responded.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      CPX\u2010351 at 44\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      daunorubicin\/dose was safe and tolerable in children with R\/R acute leukemia, showing promising activity in heavily pretreated, high\u2010risk AML and is now the FDA\u2010approved pediatric dose for therapy\u2010related AML or AML with myelodysplastic changes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70268","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:54:43Z","timestamp":1774598083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CPX\u2010351 in High\u2010Risk Relapsed Pediatric Acute Leukemia: Real\u2010World Phase 1 Data Establishing the FDA\u2010Approved Dose"],"prefix":"10.1002","volume":"73","author":[{"given":"Jonathan D.","family":"Bender","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Oncology Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Pommert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Oncology Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori R.","family":"Backus","sequence":"additional","affiliation":[{"name":"Division of Oncology Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bidwell","sequence":"additional","affiliation":[{"name":"Division of Oncology Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Blank","sequence":"additional","affiliation":[{"name":"Division of Oncology Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin H.","family":"Breese","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Oncology Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio 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M.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado and the University of Colorado Cancer Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Peck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Pediatric Cardiology University of Minnesota Masonic Children's Hospital  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Oncology Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati 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