{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:39:28Z","timestamp":1790631568799,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Treosulfan combined with fludarabine (FluTreo) has emerged as a reduced-toxicity alternative to conventional myeloablative conditioning in allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and related myeloid malignancies. Purpose: This study evaluates the safety, engraftment kinetics, and long-term outcomes of the FluTreo FT14 regimen in a real-world adult cohort. Materials and Methods: We conducted a prospective cohort study of 186 consecutive adults (18\u201370 years) undergoing allo-HCT between January 2015 and December 2024. Eligible diagnoses included de novo or secondary AML, myelodysplastic syndrome, and myelofibrosis. All received peripheral blood stem cells from matched or mismatched unrelated donors, HLA-matched siblings, or haploidentical relatives. The FT14 protocol comprised fludarabine 150 mg\/m2 over five days and treosulfan 42 g\/m2 over three days, with rabbit antithymocyte globulin (5 mg\/kg) for unrelated grafts. Primary endpoints were neutrophil and platelet engraftment, donor chimerism, incidence of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM). Kaplan\u2013Meier, Cox regression, and Fine and Gray models were applied. Results: Median age was 59 years; diagnoses included de novo AML (43%), secondary AML (16%), MDS (25%), and MF (16%). Neutrophil and platelet engraftment medians were 10 and 12 days, respectively. Full donor chimerism (\u226599%) was achieved by day 31. Grade III conditioning-related toxicity occurred in 3.2% of cases. Five-year cumulative incidences of grade II\u2013IV acute GVHD and moderate\/severe chronic GVHD were 37.6% and 30.6%. Median follow-up was 16.3 months; relapse occurred in 25.3%. Five-year OS and DFS were 71% and 49% overall (75.8% and 59% in CR1), with TRM of 15.3%. Disease relapse and acute GVHD independently predicted inferior OS, and acute GVHD predicted TRM. Conclusions: The FluTreo FT14 regimen achieves rapid engraftment, universal high donor chimerism, low severe toxicity, and durable survival, supporting its use as a myeloablative, reduced-toxicity conditioning option in myeloid malignancies.<\/jats:p>","DOI":"10.3390\/ph18111631","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"1631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Treosulfan-Based Conditioning Regimens for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Other Myeloid Malignancies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-8208","authenticated-orcid":false,"given":"Eleni","family":"Gavriilaki","sequence":"first","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"},{"name":"2nd Propaedeutic Department of Internal Medicine, Ippokratio University Hospital, Department of Medicine, Faculty of Health and Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5623-3335","authenticated-orcid":false,"given":"Panagiotis","family":"Dolgyras","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1632-821X","authenticated-orcid":false,"given":"Ioannis","family":"Konstantinidis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Mallouri","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigorios","family":"Salvaras","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2008-7954","authenticated-orcid":false,"given":"Christos","family":"Demosthenous","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Batsis","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vardi","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4699-4377","authenticated-orcid":false,"given":"Ioannis","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1703-6980","authenticated-orcid":false,"given":"Sophia","family":"Tsokkou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-6997","authenticated-orcid":false,"given":"Zoi","family":"Bousiou","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-5720","authenticated-orcid":false,"given":"Giorgos","family":"Karavalakis","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3809-0761","authenticated-orcid":false,"given":"Christos","family":"Varelas","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alkistis","family":"Panteliadou","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Spyridis","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Syrigou","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Marvaki","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Papathanasiou","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolia","family":"Papalexandri","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1244-6416","authenticated-orcid":false,"given":"Chrysavgi","family":"Lalayanni","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrysanthi","family":"Vadikoliou","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Athanasiadou","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Sakellari","sequence":"additional","affiliation":[{"name":"BMT Unit, Hematology Department, G Papanicolaou Hospital, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jtct.2024.04.014","article-title":"Treosulfan- Versus Busulfan-based Conditioning in Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Single-center Retrospective Propensity Score-matched Cohort Study","volume":"30","author":"Pasic","year":"2024","journal-title":"Transplant. Cell Ther."},{"key":"ref_2","unstructured":"Sakellari, I. (2010). Hematopoietic stem cell transplantation: Historical perspectives. New Insights in Hematopoietic Cell Transplantation, Research Signpost."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e13266","DOI":"10.1111\/petr.13266","article-title":"Outcome of treosulfan-based reduced-toxicity conditioning regimens for HSCT in high-risk patients with primary immune deficiencies","volume":"22","author":"Altun","year":"2018","journal-title":"Pediatr. Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Shimoni, A., Radici, V., and Nagler, A. (2024). Conditioning. The EBMT Handbook: Hematopoietic Cell Transplantation and Cellular Therapies, Springer International Publishing.","DOI":"10.1007\/978-3-031-44080-9_13"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7301","DOI":"10.1182\/blood-2024-211435","article-title":"Fludarabine and Treosulfan Conditioning Is Feasible and Leads to High OS and Low NRM","volume":"144","author":"Bernardi","year":"2024","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1007\/s00432-021-03836-8","article-title":"Combination of treosulfan, fludarabine and cytarabine as conditioning in patients with acute myeloid leukemia, myelodysplastic syndrome and myeloproliferative neoplasms","volume":"148","author":"Frietsch","year":"2022","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1182\/blood-2016-06-724500","article-title":"Allogeneic hematopoietic stem cell transplantation for MDS and CMML: Recommendations from an international expert panel","volume":"129","author":"Bowen","year":"2017","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41409-024-02295-2","article-title":"Comparable outcomes for TBI-based versus treosulfan based conditioning prior to allogeneic hematopoietic stem cell transplantation in AML and MDS patients","volume":"59","author":"Berning","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/ajh.27363","article-title":"Impact of busulfan versus treosulfan dose intensity in myelofibrosis undergoing hematopoietic cell transplantation","volume":"99","author":"Gagelmann","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41409-024-02269-4","article-title":"Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: A registry-based study from the Chronic Malignancies Working Party of the EBMT","volume":"59","author":"Robin","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1038\/s41409-022-01777-5","article-title":"Thiotepa\u2013fludarabine\u2013treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: A prospective multicenter phase II trial","volume":"57","author":"Finke","year":"2022","journal-title":"Bone Marrow Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/bjh.17817","article-title":"Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome using treosulfan based compared to other reduced-intensity or myeloablative conditioning regimens. A report of the chronic malignancies working party of the EBMT","volume":"195","author":"Shimoni","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lazzari, L., Ruggeri, A., Lupo Stanghellini, M.T., Mastaglio, S., Messina, C., Giglio, F., Lorusso, A., Perini, T., Piemontese, S., and Marcatti, M. (2021). Treosulfan-Based Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation: Long-Term Results From a Phase 2 Clinical Trial. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.731478"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1016\/S2352-3026(19)30157-7","article-title":"Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14\/L): A randomised, non-inferiority, phase 3 trial","volume":"7","author":"Beelen","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.bbmt.2020.02.010","article-title":"Improved Outcomes after Allogenic Hematopoietic Stem Cell Transplantation with Fludarabine\/Treosulfan for Patients with Myelodysplastic Syndromes","volume":"26","author":"Wedge","year":"2020","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00277-022-04822-x","article-title":"Conditioning with fludarabine and treosulfan compared to FLAMSA-RIC in allogeneic stem cell transplantation for myeloid malignancies: A retrospective single-center analysis","volume":"101","author":"Braitsch","year":"2022","journal-title":"Ann. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jtct.2021.07.020","article-title":"Survival Advantage of Treosulfan Plus Fludarabine Before Allogeneic Hematopoietic Cell Transplantation for Older or Comorbid Patients with Myeloid Malignancies","volume":"27","author":"Sakellari","year":"2021","journal-title":"Transplant. Cell Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1002\/cncr.30646","article-title":"Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation","volume":"123","author":"Nagler","year":"2017","journal-title":"Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.bbmt.2016.11.023","article-title":"Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation","volume":"23","author":"Sakellari","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41409-024-02241-2","article-title":"Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients\u2014A clinical trial to registry data comparison","volume":"59","author":"Beelen","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1111\/bjh.16642","article-title":"Treosulfan conditioning for allogeneic transplantation in multiple myeloma\u2014Improved overall survival in first line haematopoietic stem cell transplantation\u2014A large retrospective study by the Chronic Malignancies Working Party of the EBMT","volume":"189","author":"Gran","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3324\/haematol.2016.144428","article-title":"Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines","volume":"101","author":"Styczynski","year":"2016","journal-title":"Haematologica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.hoc.2010.11.011","article-title":"Cytomegalovirus in Hematopoietic Stem Cell Transplant Recipients","volume":"25","author":"Ljungman","year":"2011","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_25","first-page":"825","article-title":"1994 Consensus Conference on Acute GVHD Grading","volume":"15","author":"Przepiorka","year":"1995","journal-title":"Bone Marrow Transpl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S0889-8588(05)70111-8","article-title":"Pathophysiology and treatment of graft-versus-host disease","volume":"13","author":"Flowers","year":"1999","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u201cEZR\u201d for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1631\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:47:22Z","timestamp":1761760042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ph18111631"],"URL":"https:\/\/doi.org\/10.3390\/ph18111631","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}