PMID- 34568066 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220427 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - Treosulfan-Based Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation: Long-Term Results From a Phase 2 Clinical Trial. PG - 731478 LID - 10.3389/fonc.2021.731478 [doi] LID - 731478 AB - INTRODUCTION: 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. METHODS: The aim of "AlloTreo" prospective phase 2 clinical trial was to evaluate the efficacy and safety of a conditioning regimen based on Treosulfan (42 g/m(2)) and fludarabine (https://clinicaltrials.gov/ct2/show/NCT00598624). 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 (21-69) 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-versus-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%). RESULTS: 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%-50.9%), progression-free survival (PFS) was 31.7% (23%-40.7%), GvHD-free/relapse-free survival was 20.9% (13.7%-29.1%), cumulative incidence (CI) of relapse was 44.5% (34.9%-53.6%), and transplant-related mortality (TRM) was 22.5% (15.1%-30.9%). CI of acute GvHD grades II-IV was 27.8% (19.7%-36.5%) at 100 days; 12-year CI of chronic GvHD was 40.7% (31.3%-49.9%). 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 (>/=60 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. CONCLUSIONS: Overall, our data confirmed the myeloablative potential and safe toxicity profile of full dose Treo (42 g/m(2)) especially for the younger population. CI - Copyright (c) 2021 Lazzari, Ruggeri, Lupo Stanghellini, Mastaglio, Messina, Giglio, Lorusso, Perini, Piemontese, Marcatti, Lorentino, Xue, Clerici, Corti, Bernardi, Assanelli, Greco, Ciceri and Peccatori. FAU - Lazzari, Lorenzo AU - Lazzari L AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Ruggeri, Annalisa AU - Ruggeri A AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Lupo Stanghellini, Maria Teresa AU - Lupo Stanghellini MT AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Mastaglio, Sara AU - Mastaglio S AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Messina, Carlo AU - Messina C AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Giglio, Fabio AU - Giglio F AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Lorusso, Alessandro AU - Lorusso A AD - Department of Hematology, Oncology and Tumor Immunology, Charite-Universitatsmedizin Berlin, Berlin,Germany. FAU - Perini, Tommaso AU - Perini T AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Piemontese, Simona AU - Piemontese S AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Marcatti, Magda AU - Marcatti M AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Lorentino, Francesca AU - Lorentino F AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. AD - PhD Program in Public Health, Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Xue, Elisabetta AU - Xue E AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Clerici, Daniela AU - Clerici D AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Corti, Consuelo AU - Corti C AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Bernardi, Massimo AU - Bernardi M AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Assanelli, Andrea AU - Assanelli A AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Greco, Raffaella AU - Greco R AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Ciceri, Fabio AU - Ciceri F AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. AD - Universita Vita-Salute San Raffaele, Milan, Italy. FAU - Peccatori, Jacopo AU - Peccatori J AD - Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. LA - eng SI - ClinicalTrials.gov/NCT00598624 PT - Journal Article DEP - 20210910 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8461186 OTO - NOTNLM OT - ATLG OT - Treosulfan OT - allogeneic transplant OT - conditioning regimen OT - reduced toxicity COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/09/28 06:00 MHDA- 2021/09/28 06:01 PMCR- 2021/01/01 CRDT- 2021/09/27 06:15 PHST- 2021/06/27 00:00 [received] PHST- 2021/08/23 00:00 [accepted] PHST- 2021/09/27 06:15 [entrez] PHST- 2021/09/28 06:00 [pubmed] PHST- 2021/09/28 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.731478 [doi] PST - epublish SO - Front Oncol. 2021 Sep 10;11:731478. doi: 10.3389/fonc.2021.731478. eCollection 2021.