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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2002-11-3615.

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Submitted December 3, 2002
Accepted August 14, 2003

Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation

Jochen Casper*, Wolfgang Knauf, Thomas Kiefer, Daniel Wolff, Beate Steiner, Ulrich Hammer, Rudolf Wegener, Hans-Dieter Kleine, Stefan Wilhelm, Agnes Knopp, Gernot Hartung, Gottfried Dolken, and Mathias Freund

Department of Hematology and Oncology, University of Rostock, Rostock, Germany
Department of Hematology and Oncology, Klinikum Benjamin Franklin, Free University of Berlin, Berlin, Germany
Department of Hematology and Oncology, Ernst-Moritz Arndt University Greifswald, Greifswald, Germany
Department of Forensic Medicine, University of Rostock, Rostock, Germany

* Corresponding author; email: jochen.casper{at}med.uni-rostock.de.

New conditioning regimens are being explored to reduce toxicity and enable allogeneic bone marrow transplantation in patients not eligible for conventional transplantation. We have investigated treosulfan, an alkylating agent, with the aim of developing an efficient and reliable but less-toxic conditioning regimen. Thirty patients who were not eligible for standard conditioning therapy received transplants from HLA-matched related (N=14) or unrelated (N=16) donors after administration of treosulfan 10 g/m2 intravenously daily for 3 days and fludarabine 30 mg/m2 intravenously daily for 5 days. Patients receiving grafts from unrelated donors also were given rabbit antithymocyte globulin (Fresenius) 10 mg/kg intravenously daily for 3 days. All patients achieved prompt neutrophil and platelet recovery. Extramedullary toxicity was generally mild with CTC Grade 3 or 4 attributable to the conditioning seen only with transaminases. Complete donor chimerism was achieved by 90% of the patients. Acute graft-vs.-host disease (GVHD) Grade III or IV developed in 14% of the patients and chronic GVHD in 39%. An estimated overall survival rate of 73% and an event-free survival rate of 49% have been reached after a median of 22 months (range 7.4-33.4 months). In summary, the combination of treosulfan and fludarabine is a safe and efficient conditioning regimen.


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