title: Pharmacokinetically-targeted BU and fludarabine as conditioning before allogeneic hematopoietic cell transplantation for adults with ALL in first remission.
abstract: Allogeneic hematopoietic cell transplantation offers improved survival in patients with ALL, but with regimens containing TBI, the nonrelapse mortality is 20-40%. Efforts to lessen transplant toxicities by reducing conditioning regimen intensity have led to increased relapse risk. Therefore, there is a need for less toxic regimens that maintain an anti-leukemia effect. We report here a retrospective review of 65 patients with ALL in first remission receiving grafts from allogeneic donors after fludarabine 40 mg/m(2)/day for 4 days and i.v. BU targeted to a median daily area under the concentration-time curve below 6000 μmoles min/L. At 2 years after transplantation, OS was 65% (95% confidence interval (CI): 52-77%), relapse-free survival was 61% (95% CI: 48-73%), cumulative incidence of relapse was 26% (95% CI: 17-39%) and cumulative incidence of nonrelapse mortality was 14% (95% CI: 8-26%). Age over 35 years, Ph chromosome positivity and minimal residual disease at transplant did not adversely affect outcomes. Pharmacokinetically targeted BU and fludarabine can provide intensive pre-transplant conditioning for adults with ALL in first remission, with promising relapse-free and OS rates.
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: G
authors.initials: G
authors.lastname: Kunter
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Perkins
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pidala
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: T
authors.initials: T
authors.lastname: Field
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: H
authors.initials: H
authors.lastname: Fernandez
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Perez
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Locke
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Ayala
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tomblyn
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Ochoa-Bayona
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: B
authors.initials: B
authors.lastname: Betts
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nieder
authors.affiliation: 1] Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA [2] Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine