{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T19:28:56Z","timestamp":1771702136908,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Reducing toxicities while preserving efficacy in allogeneic stem cell transplant (allo-HCT) remains a particularly challenging problem. Different strategies to enhance the antitumor activity without increasing early and late adverse toxicities of the conditioning regimens have been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The aim of \u201cAlloTreo\u201d prospective phase 2 clinical trial was to evaluate the efficacy and safety of a conditioning regimen based on Treosulfan (42 g\/m<jats:sup>2<\/jats:sup>) and fludarabine (<jats:uri>https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00598624<\/jats:uri>). We enrolled 108 patients with hematological diseases who received a first allo-HCT between June 2005 and January 2011, inside the frame of this trial at our center. Median age at allo-HCT was 49 (21\u201369) years. Disease Risk Index was low in 14 (13%) patients, intermediate in 73 (67.7%), high in 17 (15.7%), and very high in 4 (3.7%). Donors were human leukocyte antigen (HLA)-matched related in 50 cases, 10\/10-matched unrelated in 36, and 9\/10-mismatched unrelated in 22. Graft-<jats:italic>versus<\/jats:italic>-host disease (GvHD) prophylaxis consisted of cyclosporine-A and methotrexate. Anti-T-lymphocyte globulin (ATLG) was administered in patients receiving unrelated allo-HCT. Stem cell source was mainly peripheral blood stem cells (95%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Conditioning regimen was well tolerated. Full donor chimerism was documented for most patients (88%) at day +30. At 12 years, overall survival (OS) was 41.7% (32.2%\u201350.9%), progression-free survival (PFS) was 31.7% (23%\u201340.7%), GvHD-free\/relapse-free survival was 20.9% (13.7%\u201329.1%), cumulative incidence (CI) of relapse was 44.5% (34.9%\u201353.6%), and transplant-related mortality (TRM) was 22.5% (15.1%\u201330.9%). CI of acute GvHD grades II\u2013IV was 27.8% (19.7%\u201336.5%) at 100 days; 12-year CI of chronic GvHD was 40.7% (31.3%\u201349.9%). Relevant long-term adverse effects were 10 secondary malignancy, 3 fatal cardiovascular events, and 1 late-onset transplant-associated thrombotic microangiopathy. Ten successful pregnancies were reported after allo-HCT. In multivariate analysis, older age (\u226560 years) at transplant [hazard ratio (HR), 2.157; p = 0.004] and a high\/very high disease risk index (HR, 1.913; p = 0.026) were significantly associated with a lower OS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, our data confirmed the myeloablative potential and safe toxicity profile of full dose Treo (42 g\/m<jats:sup>2<\/jats:sup>) especially for the younger population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.731478","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T05:42:58Z","timestamp":1631252578000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Treosulfan-Based Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation: Long-Term Results From a Phase 2 Clinical Trial"],"prefix":"10.3389","volume":"11","author":[{"given":"Lorenzo","family":"Lazzari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Ruggeri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Lupo Stanghellini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Mastaglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Messina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Giglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Lorusso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Perini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Piemontese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magda","family":"Marcatti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Lorentino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Clerici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Consuelo","family":"Corti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Bernardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Assanelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Greco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Ciceri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Peccatori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-021-01227-8","article-title":"Hematopoietic Cell Transplantation and Cellular Therapy Survey of the EBMT: Monitoring of Activities and Trends Over 30 Years","volume":"56","author":"Passweg","year":"2021","journal-title":"Bone Marrow Transplant"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003418","article-title":"How Much has Allogeneic Stem Cell Transplant-Related Mortality Improved Since the 1980s? 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