Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

B Lowenberg; W van Putten; M Theobald; J Gmur; L Verdonck; P Sonneveld; M Fey; G de Greef; A Ferrant; T Kovacsovics; A Gratwohl; S Daenen; P Huijgens; M Boogaerts; HOVON Cooperative Grp; Swiss Grp Clin Canc Res

Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

B Lowenberg^*
, W van Putten
, M Theobald
, J Gmur
, L Verdonck
, P Sonneveld
, M Fey
, G de Greef
, A Ferrant
, T Kovacsovics
, A Gratwohl
, S Daenen
, P Huijgens
, M Boogaerts
, HOVON Cooperative Grp
, Swiss Grp Clin Canc Res

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

361 Citations (Scopus)

Abstract

BACKGROUND

Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML).

METHODS

In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups.

RESULTS

After induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006).

CONCLUSIONS

Sensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML.

Original language	English
Pages (from-to)	743-752
Number of pages	10
Journal	New England Journal of Medicine
Volume	349
Issue number	8
Publication status	Published - 21-Aug-2003

Keywords

ACUTE MYELOGENOUS LEUKEMIA
HEMATOPOIETIC GROWTH-FACTORS
FACTOR GM-CSF
ACUTE MYELOBLASTIC-LEUKEMIA
DOSE ARA-C
CYTOSINE-ARABINOSIDE
ELDERLY-PATIENTS
MYELODYSPLASTIC SYNDROME
INDUCTION CHEMOTHERAPY
EUROPEAN-ORGANIZATION

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Lowenberg, B., van Putten, W., Theobald, M., Gmur, J., Verdonck, L., Sonneveld, P., Fey, M., de Greef, G., Ferrant, A., Kovacsovics, T., Gratwohl, A., Daenen, S., Huijgens, P., Boogaerts, M., HOVON Cooperative Grp, & Swiss Grp Clin Canc Res (2003). Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. New England Journal of Medicine, 349(8), 743-752.

@article{a3d2a6dd08094235ab2dfc147503e4df,

title = "Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia",

abstract = "BACKGROUNDSensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML).METHODSIn a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups.RESULTSAfter induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006).CONCLUSIONSSensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML.",

keywords = "ACUTE MYELOGENOUS LEUKEMIA, HEMATOPOIETIC GROWTH-FACTORS, FACTOR GM-CSF, ACUTE MYELOBLASTIC-LEUKEMIA, DOSE ARA-C, CYTOSINE-ARABINOSIDE, ELDERLY-PATIENTS, MYELODYSPLASTIC SYNDROME, INDUCTION CHEMOTHERAPY, EUROPEAN-ORGANIZATION",

author = "B Lowenberg and \{van Putten\}, W and M Theobald and J Gmur and L Verdonck and P Sonneveld and M Fey and \{de Greef\}, G and A Ferrant and T Kovacsovics and A Gratwohl and S Daenen and P Huijgens and M Boogaerts and \{HOVON Cooperative Grp\} and \{Swiss Grp Clin Canc Res\}",

year = "2003",

month = aug,

day = "21",

language = "English",

volume = "349",

pages = "743--752",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "MASSACHUSETTS MEDICAL SOC",

number = "8",

}

Lowenberg, B, van Putten, W, Theobald, M, Gmur, J, Verdonck, L, Sonneveld, P, Fey, M, de Greef, G, Ferrant, A, Kovacsovics, T, Gratwohl, A, Daenen, S, Huijgens, P, Boogaerts, M, HOVON Cooperative Grp & Swiss Grp Clin Canc Res 2003, 'Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia', New England Journal of Medicine, vol. 349, no. 8, pp. 743-752.

TY - JOUR

T1 - Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

AU - Lowenberg, B

AU - van Putten, W

AU - Theobald, M

AU - Gmur, J

AU - Verdonck, L

AU - Sonneveld, P

AU - Fey, M

AU - de Greef, G

AU - Ferrant, A

AU - Kovacsovics, T

AU - Gratwohl, A

AU - Daenen, S

AU - Huijgens, P

AU - Boogaerts, M

AU - HOVON Cooperative Grp

AU - Swiss Grp Clin Canc Res

PY - 2003/8/21

Y1 - 2003/8/21

N2 - BACKGROUNDSensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML).METHODSIn a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups.RESULTSAfter induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006).CONCLUSIONSSensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML.

AB - BACKGROUNDSensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML).METHODSIn a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups.RESULTSAfter induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006).CONCLUSIONSSensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML.

KW - ACUTE MYELOGENOUS LEUKEMIA

KW - HEMATOPOIETIC GROWTH-FACTORS

KW - FACTOR GM-CSF

KW - ACUTE MYELOBLASTIC-LEUKEMIA

KW - DOSE ARA-C

KW - CYTOSINE-ARABINOSIDE

KW - ELDERLY-PATIENTS

KW - MYELODYSPLASTIC SYNDROME

KW - INDUCTION CHEMOTHERAPY

KW - EUROPEAN-ORGANIZATION

M3 - Article

SN - 0028-4793

VL - 349

SP - 743

EP - 752

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 8

ER -

Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

Abstract

Keywords

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