Table 3.

Randomized, controlled, blinded clinical trials of primary antifungal prophylaxis

Prophylactic regimen and daily
dose/study arm		No.Underlying diseaseAllo/auto
SCT, %		Invasive fungal infections/
per study arm, %		Mortality, %
ProvenProbablePossibleOverallAttributable
Chandrasekar et al72 73          
 FLU 400 mg 23 91% AL, 9% other hematol NA 8.6 0 0 17.4 8.6 
 Placebo 23    4.3 0 0 13 4.3  
Goodman et al22         
 FLU 400 mg 179 NA 48/52 3 NA NA 30.7 0.6 
 Placebo 177   16 NA NA 26 5.6 
Slavin et al24 and Marr et al25         
 FLU 400 mg 152 20% AML, 10% ALL, 55% NHL + HD, 15% other 88/12 7 383-150 28 13 
 Placebo 148   18 55 55 21  
Winston et al28         
 FLU 400 mg 123 80% AML, 20% ALL NA 4 NA NA 0.8 0 
 Placebo 132   8 NA NA 3 0 
Rotstein et al26 and Laverdière et al14         
 FLU 400 mg 141 50% AML, 10% ALL, 31% other hematol, 9% solid 0/44 2.8 3.5 36 11 0.7 
 Placebo 133  tumor  16.5 7.5 26 11 4.5 
Schaffner and Schaffner27         
 FLU 400 mg 75 72% AML, 28% NHL relapse 0/10 8 2.7 6.6 5.3 2.6 
 Placebo 76   9.2 1.3 7.9 6.6 2.6 
Young et al29         
 FLU 200 mg 86 68% AML, 25% ALL, 7% other NA 4.7 NA 16 7 2 
 NYS 6 × 106IU 78   7.7 NA 24 14 4  
Huijgens et al203-151         
 FLU 100 mg 101 39% AL, 61% other hematol NA 4 7 1 7 3  
 ITR caps 200 mg 101   4 4 2 11 6  
Harousseau et al74         
 ITR oral sol 5 mg/kg 281 57% AML, 13% ALL, 29% other hematol NA 2.8 30  6 0.4  
 AmB caps 2 g PO 276   4.7 29  8 1.8  
Menichetti et al33         
 ITR oral sol 5 mg/kg + NYS 2 × 106 IU 201 76% AL, 24% other hematol NA 2.5 21  7.5 0.5  
 Placebo + NYS 2 × 106IU 204   4.4 29  8.8 2.5  
Vreugdenhil et al75         
 ITR caps 400 mg + AmB oral sol 4 g 46 64% AML, 24% ALL, 12% other hematol NA 10.9 4.3 6.5 21.7 15.2 
 Placebo + AmB oral sol 4 g 46   19.6 2.2 10.9 30.4 15.2  
Nucci et al37         
 ITR caps 200 mg 104 60% AML, 20% ALL, 18% other hematol, 2% solid NA 4.8 NA NA 7.7 1.9 
 Placebo 106  tumor  8.5 NA NA 6.6 0.9 
Kelsey et al64         
 L-AmB 2 mg/kg 3x/wk 74 27% AML, 12% ALL, 34% CML, 22% NHL/HD, 53/31 0 28.3 15 2.7  
 Placebo 87  5% other  2.3 35.6 14 2.3  
Tollemar et al61 62          
 L-AmB 1 mg/kg IV 36 25% AML, 22% ALL, 42% other hematol, 5% solid 83/NA 3 14 44 3 
 Placebo 40  tumor  8 18 36 8  
Riley et al76         
 AmB 0.1 mg/kg IV + LAF 82% 17 86% hematol, 14% solid tumor 69/NA 0 NA 29 0 0  
 Placebo + LAF 44% 18   28 NA 44 22 11 
Perfect et al53         
 AmB 0.1 mg/kg + HEPA 91 4% hematol, 96% solid tumor 0/100 1.1 NA NA 3.3 0 
 Placebo + HEPA 91   9.9 NA NA 12.1 2.2 
Prophylactic regimen and daily
dose/study arm		No.Underlying diseaseAllo/auto
SCT, %		Invasive fungal infections/
per study arm, %		Mortality, %
ProvenProbablePossibleOverallAttributable
Chandrasekar et al72 73          
 FLU 400 mg 23 91% AL, 9% other hematol NA 8.6 0 0 17.4 8.6 
 Placebo 23    4.3 0 0 13 4.3  
Goodman et al22         
 FLU 400 mg 179 NA 48/52 3 NA NA 30.7 0.6 
 Placebo 177   16 NA NA 26 5.6 
Slavin et al24 and Marr et al25         
 FLU 400 mg 152 20% AML, 10% ALL, 55% NHL + HD, 15% other 88/12 7 383-150 28 13 
 Placebo 148   18 55 55 21  
Winston et al28         
 FLU 400 mg 123 80% AML, 20% ALL NA 4 NA NA 0.8 0 
 Placebo 132   8 NA NA 3 0 
Rotstein et al26 and Laverdière et al14         
 FLU 400 mg 141 50% AML, 10% ALL, 31% other hematol, 9% solid 0/44 2.8 3.5 36 11 0.7 
 Placebo 133  tumor  16.5 7.5 26 11 4.5 
Schaffner and Schaffner27         
 FLU 400 mg 75 72% AML, 28% NHL relapse 0/10 8 2.7 6.6 5.3 2.6 
 Placebo 76   9.2 1.3 7.9 6.6 2.6 
Young et al29         
 FLU 200 mg 86 68% AML, 25% ALL, 7% other NA 4.7 NA 16 7 2 
 NYS 6 × 106IU 78   7.7 NA 24 14 4  
Huijgens et al203-151         
 FLU 100 mg 101 39% AL, 61% other hematol NA 4 7 1 7 3  
 ITR caps 200 mg 101   4 4 2 11 6  
Harousseau et al74         
 ITR oral sol 5 mg/kg 281 57% AML, 13% ALL, 29% other hematol NA 2.8 30  6 0.4  
 AmB caps 2 g PO 276   4.7 29  8 1.8  
Menichetti et al33         
 ITR oral sol 5 mg/kg + NYS 2 × 106 IU 201 76% AL, 24% other hematol NA 2.5 21  7.5 0.5  
 Placebo + NYS 2 × 106IU 204   4.4 29  8.8 2.5  
Vreugdenhil et al75         
 ITR caps 400 mg + AmB oral sol 4 g 46 64% AML, 24% ALL, 12% other hematol NA 10.9 4.3 6.5 21.7 15.2 
 Placebo + AmB oral sol 4 g 46   19.6 2.2 10.9 30.4 15.2  
Nucci et al37         
 ITR caps 200 mg 104 60% AML, 20% ALL, 18% other hematol, 2% solid NA 4.8 NA NA 7.7 1.9 
 Placebo 106  tumor  8.5 NA NA 6.6 0.9 
Kelsey et al64         
 L-AmB 2 mg/kg 3x/wk 74 27% AML, 12% ALL, 34% CML, 22% NHL/HD, 53/31 0 28.3 15 2.7  
 Placebo 87  5% other  2.3 35.6 14 2.3  
Tollemar et al61 62          
 L-AmB 1 mg/kg IV 36 25% AML, 22% ALL, 42% other hematol, 5% solid 83/NA 3 14 44 3 
 Placebo 40  tumor  8 18 36 8  
Riley et al76         
 AmB 0.1 mg/kg IV + LAF 82% 17 86% hematol, 14% solid tumor 69/NA 0 NA 29 0 0  
 Placebo + LAF 44% 18   28 NA 44 22 11 
Perfect et al53         
 AmB 0.1 mg/kg + HEPA 91 4% hematol, 96% solid tumor 0/100 1.1 NA NA 3.3 0 
 Placebo + HEPA 91   9.9 NA NA 12.1 2.2 

Allo indicates allogeneic; auto, autologous; SCT, stem cell transplantation; FLU, fluconazole; AL, acute leukemia; hematol, other hematologic disease; NA, data not available; AML, acute myelogenous leukemia; ALL, acute lymphocytic leukemia; NHL, non-Hodgkin lymphoma; HD, Hodgkin disease; NYS, nystatin; ITR, itraconazole; sol, solution; AmB, amphotericin B; L-AmB, liposomal amphotericin B; CML, chronic myelogenous leukemia; LAF laminar air flow; and HEPA, high-efficiency particulate air filter.

F3-150

Data between “Probable” column and “Possible” column indicate cases deemed “probable or possible” in studies in which no distinction was made between the two categories of likelihood.

F3-151

Huijgens et al20 used a randomized double-blind design; all other authors used a randomized double-blind placebo design.

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