{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:19:50Z","timestamp":1790421590286,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA98543"],"award-info":[{"award-number":["U10CA98543"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA98413"],"award-info":[{"award-number":["U10CA98413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180886"],"award-info":[{"award-number":["U10CA180886"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180899"],"award-info":[{"award-number":["U10CA180899"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA21765"],"award-info":[{"award-number":["CA21765"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA36401"],"award-info":[{"award-number":["CA36401"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01GM92666"],"award-info":[{"award-number":["U01GM92666"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Most patients with juvenile myelomonocytic leukemia (JMML) are curable only with allogeneic hematopoietic cell transplantation (HCT). However, the current standard conditioning regimen, busulfan\u2010cyclophosphamide\u2010melphalan (Bu\u2010Cy\u2010Mel), may be associated with higher risks of morbidity and mortality. ASCT1221 was designed to test whether the potentially less\u2010toxic myeloablative conditioning regimen containing busulfan\u2010fludarabine (Bu\u2010Flu) would be associated with equivalent outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>Twenty\u2010seven patients were enrolled on ASCT1221 from 2013 to 2015. Pre\u2010 and post\u2010HCT (starting Day +30) mutant allele burden was measured in all and pre\u2010HCT therapy was administered according to physician discretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen patients were randomized (six to Bu\u2010Cy\u2010Mel and nine to Bu\u2010Flu) after meeting diagnostic criteria for JMML. Pre\u2010HCT low\u2010dose chemotherapy did not appear to reduce pre\u2010HCT disease burden. Two patients, however, received aggressive chemotherapy pre\u2010HCT and achieved low disease\u2010burden state; both are long\u2010term survivors. All four patients with detectable mutant allele burden at Day +30 post\u2010HCT eventually progressed compared to two of nine patients with unmeasurable allele burden (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\u00a00.04). The 18\u2010month event\u2010free survival of the entire cohort was 47% (95% CI, 21\u201369%), and was 83% (95% CI, 27\u201397%) and 22% (95% CI, 03\u201351%) for Bu\u2010Cy\u2010Mel and Bu\u2010Flu, respectively (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\u00a00.04). ASCT1221 was terminated early due to concerns that the Bu\u2010Flu arm had inferior outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The regimen of Bu\u2010Flu is inadequate to provide disease control in patients with JMML who present to HCT with large burdens of disease. Advances in molecular testing may allow better characterization of biologic risk, pre\u2010HCT responses to chemotherapy, and post\u2010HCT management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.27034","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T06:46:41Z","timestamp":1520837201000},"source":"Crossref","is-referenced-by-count":37,"title":["Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: A Children's Oncology Group study"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-3952","authenticated-orcid":false,"given":"Christopher C.","family":"Dvorak","sequence":"first","affiliation":[{"name":"Division of Pediatric Allergy, Immunology &amp; Bone Marrow Transplantation Benioff Children's Hospital University of California San Francisco  San Francisco 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