{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T07:08:18Z","timestamp":1776668898969,"version":"3.51.2"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"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":["Asia-Pac J Clncl Oncology"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Allogeneic hematopoietic stem cell transplant (HSCT) is a proven curative therapy for children with high\u2010risk myeloid malignancies. Disease relapse, transplant\u2010related mortality and graft versus host disease (GvHD) are the main causes of treatment failure and death post\u2010transplant. The optimum pretransplant conditioning regimen is yet to be defined. There is limited data regarding the use of busulfan, fludarabine and melphalan as a myeloablative conditioning regimen in children receiving HSCT for myeloid malignancies.<\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n To evaluate the outcome of pharmacokinetic\u2010guided busulfan dosing, in addition to fludarabine and melphalan, as a myeloablative conditioning regimen in children with myeloid malignancies.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a retrospective, single\u2010center study of all patients <18 years of age who received busulfan, fludarabine, and melphalan conditioning prior to HSCT for myeloid malignancies between January 2013 and June 2023.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Thirteen children were included in the study. Seven were heavily pretreated with two or more lines of therapy prior to HSCT. All thirteen had neutrophil engraftment and twelve had platelet engraftment. Mucositis was the only significant regimen\u2010related toxicity, which completely resolved with standard management. Acute and chronic GVHD were seen in seven and two patients respectively, with favorable outcomes. One patient was salvaged following cytogenetic relapse, one died following morphological relapse, and one patient succumbed to infection. Eleven patients are currently alive without evidence of leukemia, myelodysplasia, or GvHD.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Busulfan, fludarabine and melphalan conditioning was well tolerated and effective, representing a suitable treatment option for heavily pretreated children with high\u2010risk myeloid malignancies prior to HSCT.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ajco.70113","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T06:21:12Z","timestamp":1776666072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myeloablative Busulfan, Fludarabine and Melphalan Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Childhood Myeloid Malignancy"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-4511","authenticated-orcid":false,"given":"Mayank","family":"Dhamija","sequence":"first","affiliation":[{"name":"Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation Perth Children's Hospital Perth Western Australia Australia"},{"name":"Medical Affairs, Hematology Oncology, ICON Biotech, ICON Plc Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Kerr","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation Perth Children's Hospital Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazel","family":"Gough","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation Perth Children's Hospital Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7247-7762","authenticated-orcid":false,"given":"Johnathan","family":"Soggee","sequence":"additional","affiliation":[{"name":"Pharmacy Department Perth Children's Hospital Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-5288","authenticated-orcid":false,"given":"Laurence C.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Leukaemia Translational Research Laboratory WA Kids Cancer Centre, The Kids Research Institute Australia Perth Western Australia Australia"},{"name":"Curtin Medical School Curtin University Perth Western Australia Australia"},{"name":"Curtin Medical Research Institute Curtin University Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1836-4075","authenticated-orcid":false,"given":"Rishi S.","family":"Kotecha","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation Perth Children's Hospital Perth Western Australia Australia"},{"name":"Leukaemia Translational Research Laboratory WA Kids Cancer Centre, The Kids Research Institute Australia Perth Western Australia Australia"},{"name":"Curtin Medical School Curtin University Perth Western Australia Australia"},{"name":"Division of Paediatrics Medical School University of Western Australia Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2837-0874","authenticated-orcid":false,"given":"Shanti","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation Perth Children's Hospital Perth Western Australia Australia"},{"name":"Division of Paediatrics Medical School University of Western Australia Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1182\/blood-2012-03-362608","article-title":"Diagnosis and Management of Acute Myeloid Leukemia in Children and Adolescents: Recommendations From an International Expert Panel","volume":"120","author":"Creutzig U.","year":"2012","journal-title":"Blood"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1038\/sj.leu.2403869","article-title":"Treatment and Long\u2010Term Results in Children With Acute Myeloid Leukaemia Treated According to the AIEOP AML Protocols","volume":"19","author":"Pession 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F.","year":"1991","journal-title":"Bone Marrow Transplantation"},{"issue":"4","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1097\/00007890-199310000-00020","article-title":"Hemorrhagic Cystitis After Bone Marrow Transplantation. Risk Factors and Complications","volume":"56","author":"Sencer S. F.","year":"1993","journal-title":"Transplantation"},{"issue":"12","key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1016\/j.bbmt.2017.07.004","article-title":"A Chemotherapy\u2010Only Regimen of Busulfan, Melphalan, and Fludarabine, and Rabbit ATG Followed by Allogeneic T\u2010Cell Depleted Hematopoietic Stem Cell Transplants for the Treatment of Myeloid Malignancies","volume":"23","author":"Spitzer B.","year":"2017","journal-title":"Biology of Blood and Marrow Transplantation"},{"issue":"7","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1038\/s41409-021-01217-w","article-title":"Adding Melphalan to Flu\u2010Darabine and a Myeloablative Dose of Busulfan Improved Survival After Allogeneic Hematopoietic Stem Cell Transplantation in a Propensity Score\u2010Matched Cohort of Hematological Malignancies","volume":"56","author":"Shimomura Y.","year":"2021","journal-title":"Bone Marrow Transplantation"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1182\/blood-2024-205008","article-title":"Conditioning With Fludarabine, Myeloablative Doses of Busulfan, and Melphalan (Flu\/Bu4\/Mel) Achieves Comparable or Superior Outcomes to Conventional Myeloablative Conditioning in Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation","volume":"144","author":"Nishino S.","year":"2024","journal-title":"Blood"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1111\/j.1399-3046.2008.00931.x","article-title":"A Conditioning Regimen of Busulfan, Fludarabine, and Melphalan for Allogeneic Stem Cell Transplantation in Children With Juvenile Myelomonocytic Leukemia","volume":"12","author":"Yabe M.","year":"2008","journal-title":"Pediatric Transplantation"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s12185-014-1715-7","article-title":"Transplantation for Juvenile Myelomonocytic Leukemia: A Retrospective Study of 30 Children Treated With a Regimen of Busulfan, Fludarabine, and Melphalan","volume":"101","author":"Yabe M.","year":"2015","journal-title":"International Journal of Hematology"},{"issue":"8","key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"e315","DOI":"10.1097\/MPH.0000000000000621","article-title":"Alternative Donor Hematopoietic Cell Transplantation Conditioned With Myeloablative Busulfan, Fludarabine, and Melphalan is Well Tolerated and Effective Against High\u2010Risk Myeloid Malignancies","volume":"38","author":"Katsanis E.","year":"2016","journal-title":"Journal of Pediatric Hematology\/Oncology"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.30102","article-title":"Busulfan, Fludarabine, and Melphalan Are Effective Conditioning for Pediatric and Young Adult Patients With Myeloid Malignancies Underdoing Matched Sibling or Alternative Donor Transplantation","volume":"70","author":"Truscott L.","year":"2023","journal-title":"Pediatric Blood & Cancer"},{"issue":"3","key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.bbmt.2015.11.010","article-title":"Haploidentical Peripheral Blood Stem Cell Transplantation With Post\u2010Transplantation Cyclophosphamide in Children With Advanced Acute Leukemia With Fludarabine\u2010, Busulfan\u2010, and Melphalan\u2010Based Conditioning","volume":"22","author":"Jaiswal S. 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J.Fraser et\u00a0al. \u201cPopulation Pharmacokinetic Model for Once\u2010Daily Intravenous Busulfan in Pediatric Subjects Describing Time\u2010Associated Clearance \u201dCPT:\u00a0Pharmacometrics\u00a0&\u00a0Systems Pharmacology11(2022):1002\u20131017.","DOI":"10.1002\/psp4.12809"},{"key":"e_1_2_8_25_1","first-page":"844","article-title":"Busulfan, Cyclophosphamide and Melphalan as Conditioning Regimen for Bone Marrow Transplantation in Children With Myelodysplastic Syndromes","volume":"8","author":"Locatelli F.","year":"1994","journal-title":"Leukemia"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1200\/JCO.1994.12.6.1217","article-title":"Allogeneic Bone Marrow Transplantation for Children With Acute Myeloblastic Leukemia in First Complete Remission: Impact of Conditioning Regimen Without Total\u2010Body Irradiation\u2013A Report From the Societe Francaise de Greffe de Moelle","volume":"12","author":"Michel G.","year":"1994","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/leu.2010.297","article-title":"Hematopoietic Stem Cell Transplantation for Advanced Myelodysplastic Syndrome in Children: Results of the EWOG\u2010MDS 98 Study","volume":"25","author":"Strahm B.","year":"2011","journal-title":"Leukemia"},{"key":"e_1_2_8_28_1","first-page":"489","article-title":"Allogeneic Bone Marrow Transplantation for Children With Acute Lymphoblastic Leukemia Conditioned With Busulfan, Cyclophosphamide and Melphalan","volume":"18","author":"Carpenter P. 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