Submitted August 1, 2007
Accepted February 19, 2008
Reduced-toxicity conditioning with fludarabine, BCNU and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematological malignancies
Reinhard Marks, Karin Potthoff, Joachim Hahn, Gabriele Ihorst, Hartmut Bertz, Alexandros Spyridonidis, Ernst Holler, and Jurgen Finke*
Department of Haematology and Oncology, Albert-Ludwigs University Medical Center, Freiburg, Germany
Department of Haematology and Oncology, University of Regensburg Medical Center, Regensburg, Germany
Institute of Medical Biometry and Medical Informatics, Albert-Ludwigs University, Freiburg, Germany
* Corresponding author; email: juergen.finke{at}uniklinik-freiburg.de.
Toxicity reduced conditioning is being used for allogeneic stem cell transplantation in older and/or comorbid patients. Here we report on the treatment of 133 patients (median age: 55.6 [23-73 years]) with AML/MDS (n=81), ALL (n=3), CML/MPS (n=20), NHL/CLL/MM (n=29) using the FBM preparative regimen: fludarabine (5x30 mg/m2), BCNU (2x200 mg/m2), melphalan (140 mg/m2). Patients 
55 years received fludarabine with reduced BCNU (2x150 mg/m2) and melphalan (110 mg/m2). After engraftment, chimerism analyses revealed complete donor hematopoiesis in 95.7% of patients. With a median follow-up of 58.5 months, 3- and 5- year overall survival (OS) was 53.0% and 46.1%, event free survival (EFS) was 46.4% and 41.9%. No significant differences in OS and EFS were evident considering disease status (early v. advanced), patient age (<55 v. 55 years), or donor (related v. unrelated) in uni- and multivariate analyses. The cumulative incidence of death due to relapse was 20.1% at 5 years. Non-relapse mortality (NRM) after 100 days and 1 year was 15.8% and 26.3%. Among patients with AML/MDS, advanced cases (n=64, including 61 patients with active disease) showed an OS of 44.6% and 42.4% after 3 and 5 years. Therefore, FBM conditioning combines effective disease control with low NRM.
