title: Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies.
abstract: Toxicity-reduced conditioning is being used for allogeneic stem cell transplantation in older and/or comorbid patients. We report on the treatment of 133 patients (median age: 55.6 years [23-73 years]) with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS; n = 81), myeloproliferative syndromes (MPS; n = 20), and lymphoid malignancies (n = 32) using conditioning with FBM: fludarabine (5 x 30 mg/m(2)), 1,3-bis(2-chloroethyl)-1-nitrosourea (or carmustine, BCNU; 2 x 200 mg/m(2)), and melphalan (140 mg/m(2)). Patients 55 years or older received fludarabine with reduced BCNU (2 x150 mg/m(2)) and melphalan (110 mg/m(2)). 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 vs advanced), patient age (<55 vs> or =55 years), or donor type (related vs unrelated) in univariate and multivariate analyses. The cumulative 5-year incidence of death due to relapse was 20.1%. Nonrelapse 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 with active disease) showed an OS of 44.6% and 42.4% after 3 and 5 years, respectively. Therefore, FBM conditioning combines effective disease control with low NRM.
authors.affiliation: Department of Haematology and Oncology, Albert-Ludwigs University Medical Center, Freiburg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Marks
authors.forename: Karin
authors.initials: K
authors.lastname: Potthoff
authors.forename: Joachim
authors.initials: J
authors.lastname: Hahn
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ihorst
authors.forename: Hartmut
authors.initials: H
authors.lastname: Bertz
authors.forename: Alexandros
authors.initials: A
authors.lastname: Spyridonidis
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Jürgen M
authors.initials: JM
authors.lastname: Finke
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002330:Carmustine / Q000008:administration & dosage; D005260:Female; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D002330:Carmustine