AUTHOR=Lazzari Lorenzo , Ruggeri Annalisa , Lupo Stanghellini Maria Teresa , Mastaglio Sara , Messina Carlo , Giglio Fabio , Lorusso Alessandro , Perini Tommaso , Piemontese Simona , Marcatti Magda , Lorentino Francesca , Xue Elisabetta , Clerici Daniela , Corti Consuelo , Bernardi Massimo , Assanelli Andrea , Greco Raffaella , Ciceri Fabio , Peccatori Jacopo 

TITLE=Treosulfan-Based Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation: Long-Term Results From a Phase 2 Clinical Trial

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.731478

DOI=10.3389/fonc.2021.731478

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><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.</p></sec><sec><title>Methods</title><p>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<sup>2</sup>) and fludarabine (<uri xlink:href="https://clinicaltrials.gov/ct2/show/NCT00598624" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/ct2/show/NCT00598624</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 (21–69) 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-<italic>versus</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%).</p></sec><sec><title>Results</title><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%–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.</p></sec><sec><title>Conclusions</title><p>Overall, our data confirmed the myeloablative potential and safe toxicity profile of full dose Treo (42 g/m<sup>2</sup>) especially for the younger population.</p></sec>