{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:59:05Z","timestamp":1764053945612,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Allogeneic hematopoietic stem cell transplantation (alloSCT) is a curative treatment for myeloid diseases, yet relapse remains the major cause of post-transplant mortality. To reduce the risk of recurrence, we evaluated the addition of 400 cGy total body irradiation (TBI) to conditioning with fludarabine-busulfan (Flu\/Bu4). Methods: In this prospective study, 46 patients with myeloid diseases were randomized to Flu\/Bu4 or Flu\/Bu4\/TBI conditioning group. The Flu\/Bu4 conditioning regimen consisted of fludarabine 40 mg\/m2 on days -6 to -3 followed by busulfan 130 mg\/m2 on days -6 to -3. Flu\/Bu4\/TBI conditioning regimen added 400 cGy TBI on day -1 to the FluBu4 regimen. Results: Among 34 acute myeloid leukemia (AML) patients, relapse was numerically lower in those who received Flu\/Bu4\/TBI (25%) versus Flu\/Bu4 (44.4%) at three years (HR = 0.58, 95% CI 0.19 to 1.81, p = 0.35). Flu\/Bu4\/TBI appeared to increase the risk of non-relapse mortality (NRM) vs. Flu\/Bu4 in AML patients at three years (25.0% versus 11.1%; HR = 2.11, 95% CI 0.51 to 8.83, p = 0.65). Overall survival (OS) was similar in AML patients undergoing conditioning with Flu\/Bu4 (72.2%) versus Flu\/Bu4\/TBI (62.5%) at one year (p = 0.4). Conclusions: In conclusion, the addition of 400 cGy TBI to Flu\/Bu4 reduced the risk of relapse but did not improve OS as a consequence of higher regimen-related mortality. Clinicaltrials.gov identifier: NCT01366612.<\/jats:p>","DOI":"10.3390\/cancers17071140","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"1140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prospective, Randomized, Comparative Study of Myeloablative Fludarabine\/Busulfan and Fludarabine\/Busulfan\/Total Body Irradiation Conditioning in Myeloid Diseases"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6912-4157","authenticated-orcid":false,"given":"Hyung C.","family":"Suh","sequence":"first","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-835X","authenticated-orcid":false,"given":"Scott D.","family":"Rowley","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"},{"name":"MedStar Georgetown University Hospital, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7689-5882","authenticated-orcid":false,"given":"Sukhdeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittany","family":"Lukasik","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phyllis","family":"McKiernan","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Boonstra","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Baker","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"DiLorenzo","sequence":"additional","affiliation":[{"name":"Novant Health, Charlotte, NC 28204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Skarbnik","sequence":"additional","affiliation":[{"name":"Novant Health, Charlotte, NC 28204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Voss","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0875-6489","authenticated-orcid":false,"given":"Alexandra","family":"Hampson","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4704-2076","authenticated-orcid":false,"given":"Bianca","family":"DeAgresta","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brighid","family":"Boylan","sequence":"additional","affiliation":[{"name":"Hackensack Meridian School of Medicine, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Themba","family":"Nyirenda","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Bioinformatics, and Biomathematics, Hackensack University Medical Center, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Vesole","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"},{"name":"MedStar Georgetown University Hospital, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4678-5849","authenticated-orcid":false,"given":"Michele L.","family":"Donato","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.3324\/haematol.2020.248187","article-title":"Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades","volume":"106","author":"Cooper","year":"2021","journal-title":"Haematologica"},{"doi-asserted-by":"crossref","unstructured":"Lipof, J.J., Loh, K.P., O\u2019Dwyer, K., and Liesveld, J.L. (2018). Allogeneic hematopoietic cell transplantation for older adults with acute myeloid leukemia. Cancers, 10.","key":"ref_2","DOI":"10.3390\/cancers10060179"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/bmt.2017.83","article-title":"Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemia","volume":"52","author":"Jethava","year":"2017","journal-title":"Bone Marrow Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s11899-018-0462-x","article-title":"Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia; current evidence, and improving outcomes going forward","volume":"13","author":"Leonard","year":"2018","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3324\/haematol.2015.123331","article-title":"Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission\u2014A review from the Acute Leukemia Working Party of the EBMT","volume":"100","author":"Sengsayadeth","year":"2015","journal-title":"Haematologica"},{"unstructured":"Bolon, Y.T., Atshan, A.R., Allbee-Johnson, M., Estrada-Merly, N., and Lee, S.J. (2025, February 20). Current Uses and Outcomes of Hematopoietic Stem Cell Transplantation in the U.S. Available online: https:\/\/cibmtr.org\/CIBMTR\/Resources\/Summary-Slides-Reports.","key":"ref_6"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1200\/JCO.20.02308","article-title":"Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia","volume":"39","author":"Craddock","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1200\/JCO.2016.70.7091","article-title":"Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes","volume":"35","author":"Scott","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"483.e1","DOI":"10.1016\/j.jtct.2021.02.031","article-title":"Myeloablative versus reduced-intensity conditioning for hematopoietic cell transplantation in acute myelogenous leukemia and myelodysplastic syndromes\u2013long-term follow-up of the BMT CTN 0901 clinical trial","volume":"27","author":"Scott","year":"2021","journal-title":"Transplant. Cell. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/S0360-3016(00)01491-7","article-title":"Total body irradiation before allogeneic bone marrow transplantation: Is more dose better?","volume":"49","author":"Bieri","year":"2001","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1182\/blood.V76.9.1867.1867","article-title":"Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: A randomized trial of two irradiation regimens","volume":"76","author":"Clift","year":"1990","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1016\/j.bbmt.2019.08.012","article-title":"Comparison of high doses of total body irradiation in myeloablative conditioning before hematopoietic cell transplantation","volume":"25","author":"Sabloff","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.bbmt.2017.11.025","article-title":"Intravenous busulfan compared with total body irradiation pretransplant conditioning for adults with acute lymphoblastic leukemia","volume":"24","author":"Kebriaei","year":"2018","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1056\/NEJM198312013092202","article-title":"Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide","volume":"309","author":"Santos","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/01.cad.0000127145.50172.51","article-title":"Intraindividual variability in busulfan pharmacokinetics in patients undergoing a bone marrow transplant: Assessment of a test dose and first dose strategy","volume":"15","author":"Lindley","year":"2004","journal-title":"Anticancer Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0301-472X(03)00047-X","article-title":"Intravenous busulfan-based conditioning prior to allogeneic hematopoietic stem cell transplantation: Myeloablation with reduced toxicity","volume":"31","author":"Shimoni","year":"2003","journal-title":"Exp. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1756-8722-6-15","article-title":"Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: A prospective and multicenter study","volume":"6","author":"Liu","year":"2013","journal-title":"J. Hematol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.bbmt.2009.11.017","article-title":"The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia","volume":"16","author":"Russell","year":"2010","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.bbmt.2015.09.001","article-title":"International, multicenter standardization of acute graft-versus-host disease clinical data collection: A report from the Mount Sinai Acute GVHD International Consortium","volume":"22","author":"Harris","year":"2016","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.bbmt.2014.12.035","article-title":"2014 National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Preface to the series","volume":"21","author":"Pavletic","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1182\/blood-2005-05-2004","article-title":"Hematopoietic cell transplantation (HCT)-specific comorbidity index: A new tool for risk assessment before allogeneic HCT","volume":"106","author":"Sorror","year":"2005","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/bmt.2016.42","article-title":"Toxicity and efficacy of busulfan and fludarabine myeloablative conditioning for HLA-identical sibling allogeneic hematopoietic cell transplantation in AML and MDS","volume":"51","author":"Sanz","year":"2016","journal-title":"Bone Marrow Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.hemonc.2019.09.002","article-title":"Comparative effectiveness of busulfan\/cyclophosphamide versus busulfan\/fludarabine myeloablative conditioning for allogeneic hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome","volume":"13","author":"Patel","year":"2020","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/s41409-022-01705-7","article-title":"A randomized phase III study of pretransplant conditioning for AML\/MDS with fludarabine and once daily IV busulfan +\/\u2212 clofarabine in allogeneic stem cell transplantation","volume":"57","author":"Andersson","year":"2022","journal-title":"Bone Marrow Transplant."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.bbmt.2017.12.785","article-title":"Transplant conditioning with treosulfan\/fludarabine with or without total body irradiation: A randomized phase II trial in patients with myelodysplastic syndrome and acute myeloid leukemia","volume":"24","author":"Deeg","year":"2018","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1182\/blood.2018874115","article-title":"Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation","volume":"133","author":"Baker","year":"2019","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1182\/bloodadvances.2020003910","article-title":"Cumulative incidence of subsequent malignancy after allo-HCT conditioned with or without low-dose total body irradiation","volume":"6","author":"Nunez","year":"2022","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1016\/j.bbmt.2013.07.002","article-title":"Establishing a target exposure for once-daily intravenous busulfan given with fludarabine and thymoglobulin before allogeneic transplantation","volume":"19","author":"Russell","year":"2013","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e14018","DOI":"10.1111\/ctr.14018","article-title":"Hematopoietic cell transplant outcomes after myeloablative conditioning with fludarabine, busulfan, low-dose total body irradiation, and rabbit antithymocyte globulin","volume":"34","author":"Ousia","year":"2020","journal-title":"Clin. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"865","DOI":"10.3324\/haematol.2016.159343","article-title":"Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: A meta-analysis","volume":"102","author":"Buckley","year":"2017","journal-title":"Haematologica"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1001\/jamaoncol.2020.4600","article-title":"Association of measurable residual disease With survival outcomes in patients with acute myeloid leukemia: A systematic review and meta-analysis","volume":"6","author":"Short","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1200\/JCO.2015.63.3826","article-title":"Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: Time to move toward a minimal residual disease-based definition of complete remission?","volume":"34","author":"Araki","year":"2016","journal-title":"J. Clin. Oncol."},{"doi-asserted-by":"crossref","unstructured":"Morsink, L.M., Sandmaier, B.M., Othus, M., Palmieri, R., Granot, N., Bezerra, E.D., Wood, B.L., Mielcarek, M., Schoch, G., and Davis, C. (2020). Conditioning intensity, pre-transplant flow cytometric measurable residual disease, and outcome in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Cancers, 12.","key":"ref_34","DOI":"10.3390\/cancers12092339"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1182\/bloodadvances.2020003195","article-title":"Measurable residual disease in elderly acute myeloid leukemia: Results from the PETHEMA-FLUGAZA phase 3 clinical trial","volume":"5","author":"Simoes","year":"2021","journal-title":"Blood Adv."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/7\/1140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:04:23Z","timestamp":1760029463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/7\/1140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["cancers17071140"],"URL":"https:\/\/doi.org\/10.3390\/cancers17071140","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2025,3,28]]}}}