title: Long-term follow-up of a phase I study of high-dose decitabine, busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias.
abstract: BACKGROUND
  Decitabine is a hypomethylating agent that has activity in patients with leukemia. The authors combined decitabine with busulfan and cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation.
  
  
  METHODS
  Patients with high-risk acute myeloid leukemia (AML) (n = 12 patients); chronic myelomonocytic leukemia (CMML) (n = 1 patient); acute lymphocytic leukemia (ALL) (n = 1 patient); or late chronic phase, accelerated, or blastic phase chronic myelogenous leukemia (n = 9 patients) were eligible for the study. The treatment plan was comprised of busulfan, 12 mg/kg orally; cyclophosphamide, 100 mg/kg (n = 4 patients) or 120 mg/kg (n = 19 patients); and decitabine, intravenously at 3 dose levels: 400 mg/m(2) (n = 10 patients), 600 mg/m(2) (n = 8 patients), and 800 mg/m(2) (n = 5 patients). Donors were human leukocyte antigen-identical siblings in all cases, and all but one patient received peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus based in all but one patient.
  
  
  RESULTS
  The median time to neutrophil and platelet engraftment was 12.5 days and 17.5 days, respectively. Twenty-one patients were engrafted and achieved disease remission. At a median of 3.3 years posttransplantation, 26% of patients (40% of patients with AML) were alive and disease free. The median survival for the group was 17.2 months, and the disease free survival for the group was 8.9 months. Causes of death were disease recurrence (nine patients), chronic GVHD (four patients), infections (three patients), and acute GVHD (one patient). The 100-day mortality rate was 9%. No decitabine dose-limiting toxicity was documented. The treatment-related mortality rate at 3 years was 35%. Responders were treated at all three decitabine dose levels, and no dose-response correlation was observed.
  
  
  CONCLUSIONS
  There was a high response rate with low treatment-related mortality, with 26% of patients alive in remission 3.3 years after transplantation.
authors.affiliation: Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA. mdelima@mdanderson.org
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Munir
authors.initials: M
authors.lastname: Shahjahan
authors.forename: Borje
authors.initials: B
authors.lastname: Andersson
authors.forename: Daniel
authors.initials: D
authors.lastname: Couriel
authors.forename: Michele
authors.initials: M
authors.lastname: Donato
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077209:Decitabine; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning
chemical_list: D000077209:Decitabine; D003520:Cyclophosphamide; D002066:Busulfan; D001374:Azacitidine