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

Marcos De Lima, Farhad Ravandi, Munir Shahjahan, Borje Andersson, Daniel Couriel, Michele Donato, Issa Khouri, James Gajewski, Koen Van Besien, Richard Champlin, Sergio Giralt, Hagop Kantarjian

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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/m2 (n = 10 patients), 600 mg/m2 (n = 8 patients), and 800 mg/m2 (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.

Original languageEnglish (US)
Pages (from-to)1242-1247
Number of pages6
JournalCancer
Volume97
Issue number5
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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decitabine
Busulfan
Homologous Transplantation
Cyclophosphamide
Leukemia
Therapeutics
Graft vs Host Disease

Keywords

  • Acute myelogenous leukemia
  • Allogeneic transplant
  • Decitabine
  • Leukemias

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / De Lima, Marcos; Ravandi, Farhad; Shahjahan, Munir; Andersson, Borje; Couriel, Daniel; Donato, Michele; Khouri, Issa; Gajewski, James; Van Besien, Koen; Champlin, Richard; Giralt, Sergio; Kantarjian, Hagop.

In: Cancer, Vol. 97, No. 5, 01.03.2003, p. 1242-1247.

Research output: Contribution to journalArticle

De Lima, M, Ravandi, F, Shahjahan, M, Andersson, B, Couriel, D, Donato, M, Khouri, I, Gajewski, J, Van Besien, K, Champlin, R, Giralt, S & Kantarjian, H 2003, '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', Cancer, vol. 97, no. 5, pp. 1242-1247. https://doi.org/10.1002/cncr.11184
De Lima, Marcos ; Ravandi, Farhad ; Shahjahan, Munir ; Andersson, Borje ; Couriel, Daniel ; Donato, Michele ; Khouri, Issa ; Gajewski, James ; Van Besien, Koen ; Champlin, Richard ; Giralt, Sergio ; Kantarjian, Hagop. / 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. In: Cancer. 2003 ; Vol. 97, No. 5. pp. 1242-1247.
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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/m2 (n = 10 patients), 600 mg/m2 (n = 8 patients), and 800 mg/m2 (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.",
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T1 - 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

AU - De Lima, Marcos

AU - Ravandi, Farhad

AU - Shahjahan, Munir

AU - Andersson, Borje

AU - Couriel, Daniel

AU - Donato, Michele

AU - Khouri, Issa

AU - Gajewski, James

AU - Van Besien, Koen

AU - Champlin, Richard

AU - Giralt, Sergio

AU - Kantarjian, Hagop

PY - 2003/3/1

Y1 - 2003/3/1

N2 - 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/m2 (n = 10 patients), 600 mg/m2 (n = 8 patients), and 800 mg/m2 (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.

AB - 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/m2 (n = 10 patients), 600 mg/m2 (n = 8 patients), and 800 mg/m2 (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.

KW - Acute myelogenous leukemia

KW - Allogeneic transplant

KW - Decitabine

KW - Leukemias

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