title: Reduced-intensity conditioning allogeneic blood stem cell transplantation with fludarabine and oral busulfan with or without pharmacokinetically targeted busulfan dosing in patients with myeloid leukemia ineligible for conventional conditioning.
abstract: We prospectively compared outcomes after a fludarabine (Flu) plus oral busulfan (Bu)-containing reduced-intensity conditioning regimen (150 mg/m2 Flu and 10 mg/kg oral Bu), with (n = 32; Flu- T Bu group) or without (n = 30; Flu-Bu group) therapeutic dose monitoring and dose adjustment of Bu. All patients received peripheral blood stem cells from a genoidentical sibling, and study cohorts had similar patient characteristics. Dose adjustments of Bu were required in 20 (63%) patients in the Flu- T Bu group (median final dose, 8.89 mg/kg; range, 6.3-13.34 mg/kg). Donor T-cell and granulocyte engraftments were similar, and early conditioning-related toxicities were mild and similar in both study groups. With a median follow-up of 45 months (51 months in the 37 survivors), posttransplantation outcomes did not differ between cohorts. The strongest predictor of 2-year overall survival and leukemia-free survival was the presence of chronic graft-versus-host disease (77% versus 34% for overall survival and 74% versus 34% for leukemia-free survival; P < .001 for both outcomes). In conclusion, therapeutic dose monitoring of oral Bu in a reduced-intensity conditioning setting does not seem to affect outcome, although further studies may identify very-high-risk patients who benefit from this strategy.
authors.affiliation: Division of Clinical Hematology, Hospital de la Sant Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain. rmartino@hsp.santpau.es
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: José A
authors.initials: JA
authors.lastname: Pérez-Simón
authors.forename: Estela
authors.initials: E
authors.lastname: Moreno
authors.forename: José M
authors.initials: JM
authors.lastname: Queraltó
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.forename: Marivi
authors.initials: M
authors.lastname: Mateos
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Consuelo
authors.initials: C
authors.lastname: Cañizo
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: Lourdes
authors.initials: L
authors.lastname: Vazquez
authors.forename: Ana
authors.initials: A
authors.lastname: Clopés
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007951:Leukemia, Myeloid / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine