Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia.
OBJECTIVE
The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality.


METHODS
We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 microg/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60).


RESULTS
The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT.


CONCLUSIONS
Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML.
Löwenberg
B
B
Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and Swiss Group for Clinical Cancer Research: Daniel den Hoed Cancer Center Rotterdam, The Netherlands. lowenberg@haed.azr.nl
Boogaerts
M A
MA
Daenen
S M
SM
Verhoef
G E
GE
Hagenbeek
A
A
Vellenga
E
E
Ossenkoppele
G J
GJ
Huijgens
P C
PC
Verdonck
L F
LF
van der Lelie
J
J
Wielenga
J J
JJ
Schouten
H C
HC
Gmür
J
J
Gratwohl
A
A
Hess
U
U
Fey
M F
MF
van Putten
W L
WL
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D018572:Disease-Free Survival; D005069:Evaluation Studies as Topic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
D016178:Granulocyte-Macrophage Colony-Stimulating Factor