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: Reinhard Marks, Karin Potthoff, Joachim Hahn, Gabriele Ihorst, Hartmut Bertz, Alexandros Spyridonidis, Ernst Holler, Jürgen M Finke
• Journal: Blood (Blood) Vol. 112 Issue 2 Pg. 415-25 (Jul 15 2008) ISSN: 1528-0020 [Electronic] United States
• PMID: 18451310 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Vidarabine
• fludarabine
• Melphalan
• Carmustine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use, toxicity)
• Carmustine (administration & dosage)
• Female
• Hematologic Neoplasms (mortality, therapy)
• Hematopoietic Stem Cell Transplantation (methods, mortality)
• Humans
• Male
• Melphalan (administration & dosage)
• Middle Aged
• Survival Analysis
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Vidarabine (administration & dosage, analogs & derivatives)