PURPOSE: Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 x 10 g/m(2) was the basis for dose escalation in this prospective, multicenter trial. PATIENTS AND METHODS: Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m(2), 12 g/m(2), or 14 g/m(2) of intravenous treosulfan, which was administered on days -6 to -4 combined with fludarabine 30 mg/m(2) on days -6 to -2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%). RESULTS: No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568). CONCLUSION: Treosulfan-based conditioning was feasible at all three doses. The 3 x 14 g/m(2) dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate.
PURPOSE:Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 x 10 g/m(2) was the basis for dose escalation in this prospective, multicenter trial. PATIENTS AND METHODS: Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m(2), 12 g/m(2), or 14 g/m(2) of intravenous treosulfan, which was administered on days -6 to -4 combined with fludarabine 30 mg/m(2) on days -6 to -2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%). RESULTS: No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568). CONCLUSION:Treosulfan-based conditioning was feasible at all three doses. The 3 x 14 g/m(2) dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate.
Authors: M Hahn; S Böttcher; S Dietrich; U Hegenbart; M Rieger; P Stadtherr; A Bondong; R Schulz; M Ritgen; T Schmitt; T H Tran; M Görner; I Herth; T Luft; S Schönland; M Witzens-Harig; T Zenz; M Kneba; A D Ho; P Dreger Journal: Bone Marrow Transplant Date: 2015-07-06 Impact factor: 5.483
Authors: Tapani Ruutu; Liisa Volin; Dietrich W Beelen; Rudolf Trenschel; Juergen Finke; Marc Schnitzler; Jerzy Holowiecki; Sebastian Giebel; Miroslaw Markiewicz; Lutz Uharek; Igor W Blau; Joachim Kienast; Matthias Stelljes; Kajsa Larsson; Axel R Zander; Martin Gramatzki; Roland Repp; Hermann Einsele; Gernot Stuhler; Joachim Baumgart; Heidrun A Mylius; Uwe Pichlmeier; Mathias Freund; Jochen Casper Journal: Haematologica Date: 2011-06-09 Impact factor: 9.941
Authors: Eneida R Nemecek; Ralf A Hilger; Alexia Adams; Bronwen E Shaw; Deidre Kiefer; Jennifer Le-Rademacher; John E Levine; Gregory Yanik; Wing Leung; Julie-An Talano; Paul Haut; David Delgado; Neena Kapoor; Aleksandra Petrovic; Roberta Adams; Rabi Hanna; Hemalatha Rangarajan; Jignesh Dalal; Joseph Chewning; Michael R Verneris; Stacy Epstein; Lauri Burroughs; Evelio D Perez-Albuerne; Michael A Pulsipher; Colleen Delaney Journal: Biol Blood Marrow Transplant Date: 2018-05-09 Impact factor: 5.742
Authors: M Koenigsmann; J Casper; C Kahl; N Basara; H G Sayer; G Behre; S Theurich; M Christopeit; M Mohren; A Reichle; B Metzner; A Ganser; M Stadler; L Uharek; L Balleisen; A Hinke; R Hinke; D Niederwieser Journal: Bone Marrow Transplant Date: 2013-12-23 Impact factor: 5.483
Authors: Michael Schmitt; Rudolf Trenschel; Herbert G Sayer; Catarina Schneider; Aenne Glass; Inken Hilgendorf; Anne Treschl; Christian Junghanss; Kersten Borchert; Michael Koenigsmann; Jochen Casper; Dietrich W Beelen; Mathias Freund; Christoph Kahl Journal: Mol Clin Oncol Date: 2014-06-02