18735
document
Treatment of severe aplastic anemia with antilymphocyte globulin , cyclosporine and two different granulocyte colony-stimulating factor regimens : a GITMO prospective randomized study . BACKGROUND AND OBJECTIVES In a previous study we showed that patients with severe aplastic anemia ( SAA ) treated with anti-lymphocyte globulin ( ALG ) , cyclosporin ( CyA ) and granulocyte colony-stimulating factor ( G-CSF ) 5 micro g/kg/day had an encouraging outcome . However , failure to respond , delayed responses , partial responses , relapses and early deaths remain significant problems . The aim of the present study was to test whether a higher dose of G-CSF ( 10 micro g/kg/day ) would reduce these complications . DESIGN AND METHODS This was a multicenter prospective trial in 77 SAA patients treated with horse ALG ( 15 mg/kg/day day1-5 ) and CyA ( 5 mg/kg/day day 1-180 ) . Patients were randomized to receive G-CSF 5 micro g/kg/day ( n=38 , group A ) or 10 micro g/kg/day ( n=39 , group B ) from day +1 to day +30 . All patients then received G-CSF 5 micro g/kg/day from day +31 to day +90 . The primary end point of this study was response at day +120 . Secondary end points were early deaths , blood counts at day +120 , and survival . RESULTS At day +120 responses were classified as absent , partial , and complete in 12 , 22 , and 4 patients in group A and in 23 , 7 , and 9 patients in group B ( p=0.001 ) . At last follow-up these figures were respectively 9 , 12 , and 17 vs 19 , 2 , and 18 ( p=0.004 ) . Thirteen patients ( 5 in group A and 8 in group B ) died before day 120 ( p=0.3 ) . Median peripheral blood counts on day 120 were comparable in the two groups : Hb 10.5 and 9.5 g/dL in group A and B , respectively ( p=0.6 ) , Neutrophil counts were 2.4 vs 1.9x10 ( 9 ) /L in groups A and B ( p=0.4 ) and platelet counts were , respectively , 42 vs 36x10 ( 9 ) /L ( p=0.3 ) . The actuarial survival at 4 years is 72 % in group A and 67 % in group B ( p=0.3 ) . INTERPRETATION AND CONCLUSIONS Increasing the dose of G-CSF does not appear to reduce early deaths , does not improve peripheral blood counts nor survival , and may reduce the response rate in patients with SAA receiving ALG and CyA .
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Intervention_Pharmacological
antilymphocyte globulin
18737
Intervention_Pharmacological
cyclosporine
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Intervention_Pharmacological
granulocyte colony-stimulating factor regimens
18739
Intervention_Pharmacological
anti-lymphocyte globulin ( ALG
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Intervention_Pharmacological
cyclosporin ( CyA )
18741
Intervention_Pharmacological
granulocyte colony-stimulating factor ( G-CSF )
18742
Intervention_Physical
G-CSF
18743
Intervention_Pharmacological
horse ALG ( 15 mg/kg/day day1-5 )
18744
Intervention_Pharmacological
CyA ( 5 mg/kg/day day 1-180 )
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Intervention_Pharmacological
receive G-CSF 5 micro g/kg/day ( n=38 , group A ) or 10 micro g/kg/day ( n=39 , group B ) from day +1 to day +30 .
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Intervention_Pharmacological
G-CSF 5
18747
Intervention_Physical
G-CSF
18748
Intervention_Pharmacological
ALG
18749
Intervention_Pharmacological
CyA
18750
Outcome_Other
failure to respond , delayed responses , partial responses , relapses
18751
Outcome_Mortality
early deaths
18752
Outcome_Adverse-effects
reduce these complications .
18753
Outcome_Other
response
18754
Outcome_Mortality
early deaths ,
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Outcome_Physical
blood counts
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Outcome_Mortality
survival .
18757
Outcome_Mental
responses
18758
Outcome_Mental
absent , partial
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Outcome_Other
complete
18760
Outcome_Mortality
died
18761
Outcome_Physical
peripheral blood counts
18762
Outcome_Physical
Neutrophil counts
18763
Outcome_Physical
platelet counts
18764
Outcome_Mortality
actuarial survival
18765
Outcome_Mortality
reduce early deaths
18766
Outcome_Physical
peripheral blood counts
18767
Outcome_Mortality
survival
18768
Outcome_Other
response rate
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Participant_Condition
patients with severe aplastic anemia ( SAA ) treated with anti-lymphocyte globulin ( ALG ) , cyclosporin ( CyA ) and granulocyte colony-stimulating factor ( G-CSF )
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Participant_Sample-size
77