Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies

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 myelold leukemia (AML)/myelodysplastic syndrome (MDS; In = 81), myeloprol iterative syndromes (MPS; n = 20), and lymphoid malignancies (n = 32) using conditioning with FBIVI: fludarabine (5 x 30 mg/m(2)), 1,3-bis(2-chloroethyl)-lnitrosourea (or carmustine, BCNU; 2 x 200 Mg/M2), and melphalan (140 mg/m(2)). Patients 55 years or older received fludarabine with reduced BCNU (2 x 150 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 followup of 58.5 months, 3- and 5-year overall survival (OS) was 53.0% and 46.1 %, eventfree 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 >= 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 AMUMDS, 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, FBIVI conditioning combines effective disease control with low NRM.