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.
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.
de Lima
Marcos
M
Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA. mdelima@mdanderson.org
Ravandi
Farhad
F
Shahjahan
Munir
M
Andersson
Borje
B
Couriel
Daniel
D
Donato
Michele
M
Khouri
Issa
I
Gajewski
James
J
van Besien
Koen
K
Champlin
Richard
R
Giralt
Sergio
S
Kantarjian
Hagop
H
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
D000077209:Decitabine; D003520:Cyclophosphamide; D002066:Busulfan; D001374:Azacitidine