Randomized, controlled, open clinical trials of primary antifungal prophylaxis
| Prophylactic regimen and daily dose/study arm . | No. . | Underlying disease . | Allo/auto SCT, % . | Invasive fungal infections/ study arm, % . | Mortality, % . | |||
|---|---|---|---|---|---|---|---|---|
| Proven . | Probable . | Possible . | Overall . | Attributable . | ||||
| MacMillan et al77 | ||||||||
| FLU 400 mg PO | 124 | 36% AL, 25% CML, 17% NHL/HD | 56/44 | 7.3 | NA | NA | NA | NA |
| FLU 200 mg PO | 129 | 2.3 | NA | NA | NA | NA | ||
| Egger et al78 | ||||||||
| FLU 400 mg PO/IV | 43 | 46% AL, 18% CML, 16% NHL/HD | NA | NA | NA | NA | NA | 2.3 |
| NYS 72 × 106 IU PO + MCZ inhalation, dose NA | 46 | NA | NA | NA | NA | 0 | ||
| Bodey et al55 | ||||||||
| FLU 400 mg | 41 | 94% AML, 6% ALL | NA | 4.8 | 7.3 | 4.8 | 14.6 | 0 |
| AmB 0.5 mg/kg 3x/wk IV | 36 | 8.3 | 19.4 | 2.7 | 25 | 2.7 | ||
| Wolff et al54 | ||||||||
| FLU 400 mg | 196 | NA | 29/71 | 4.1 | NA | NA | 12.2 | 2.6 |
| AmB 0.2 mg/kg/d IV | 159 | 7.5 | NA | NA | 11.9 | 1.3 | ||
| Winston et al35 | ||||||||
| FLU 400 mg IV od PO | 67 | NA | 100/0 | 25 | NA | NA | NA | 18 |
| d 1–2: ITR 400 mg IV; d 3, ITR 200 IV or ITR 400 sol | 71 | 9 | NA | NA | NA | 9 | ||
| Kern et al79 | ||||||||
| FLU 400 mg + AmB 240 mg PO | 36 | 100% AML relapse | NA | 5.6 | 0 | 53 | 22 | 0 |
| AmB 240 mg PO | 32 | 6.3 | 0 | 34 | 19 | 0 | ||
| Ninane80 | ||||||||
| FLU 3 mg/kg | 245 | 53% AL, 12% NHL/HD, 30% other | NA | 0.8 | NA | NA | 1.2 | NA |
| NYS 0.2 × 106 IU/kg +/− AmB 100 mg/kg | 257 | 1.9 | NA | NA | 2.3 | NA | ||
| Ellis et al81 82 | ||||||||
| FLU 200 mg | 42 | 47% AML, 30% ALL, 8% NHL/HD, 16% | 26/NA | 4.8 | 2.3 | NA | NA | 4.8 |
| CLO 20 mg + NYS 2 × 106IU | 48 | other | 21 | 2.1 | NA | NA | 18.8 | |
| Menichetti et al30 | ||||||||
| FLU 150 mg | 420 | 81% AML, 19% ALL | NA | 2.6 | NA | 16 | 10.5 | 1.2 |
| AmB oral sol 2 g | 400 | 2.5 | NA | 21 | 10 | 0.8 | ||
| Philpott-Howard et al23 and Rozenberg-Arska et al47 | ||||||||
| FLU 50 mg | 256 | 76% AL, 22% other hematol, 2% solid | 21/NA | 2.4 | NA | NA | NA | NA |
| AmB oral sol 2 g or NYS 4 × 106IU | 255 | tumor | 3.5 | NA | NA | NA | NA | |
| Boogaerts et al34 | ||||||||
| ITR oral sol 200 mg | 144 | 66% AML | 9/0 | 5 | 34-151 | 11.8 | 4.1 | |
| AmB caps 1500 mg + NYS 2 × 106IU | 133 | 5 | 4 | 12.8 | 4.5 | |||
| Morgenstern et al31 | ||||||||
| ITR oral sol 5 mg/kg | 288 | 53% AML, 12% ALL, 35% other hematol | NA | 0.3 | 3.1 | NA | 0 | |
| FLU 100 mg | 293 | 2 | 2.4 | NA | 2.4 | |||
| Annaloro et al834-150 | ||||||||
| ITR caps 400 mg + NYS, dose NA | 31 | NA | 35/65 | 12.9 | 3.2 | 6.4 | 0 | |
| FLU 300 mg + NYS, dose NA | 28 | 3.6 | 7.1 | 7.1 | 0 | |||
| FLU 50 mg + NYS, dose NA | 30 | 3.3 | 6.6 | 3.3 | 0 | |||
| Timmers et al65 | ||||||||
| ABCD 2 mg/kg IV | 12 | 25% AML, 8% ALL, 67% other hematol | 0/0 | 0 | NA | NA | 17 | 0 |
| FLU 200 mg | 12 | 0 | NA | NA | 0 | 0 | ||
| Schwartz et al32 | ||||||||
| AmB 20 mg inhalation | 227 | 74% AML, 9% ALL/NHL relapse | 0/17 | 1.8 | 2.2 | 0.4 | 13 | 8 |
| No prophylaxis | 155 | 0.6 | 5.8 | 0.6 | 10 | 7 | ||
| Buchanan et al49 | ||||||||
| NYS 6 × 106 IU PO | 104 | 30% AML, 7% ALL, 29% NHL/HD | NA | NA | NA | NA | NA | NA |
| No prophylaxis | 60 | NA | NA | NA | NA | NA | ||
| Prophylactic regimen and daily dose/study arm . | No. . | Underlying disease . | Allo/auto SCT, % . | Invasive fungal infections/ study arm, % . | Mortality, % . | |||
|---|---|---|---|---|---|---|---|---|
| Proven . | Probable . | Possible . | Overall . | Attributable . | ||||
| MacMillan et al77 | ||||||||
| FLU 400 mg PO | 124 | 36% AL, 25% CML, 17% NHL/HD | 56/44 | 7.3 | NA | NA | NA | NA |
| FLU 200 mg PO | 129 | 2.3 | NA | NA | NA | NA | ||
| Egger et al78 | ||||||||
| FLU 400 mg PO/IV | 43 | 46% AL, 18% CML, 16% NHL/HD | NA | NA | NA | NA | NA | 2.3 |
| NYS 72 × 106 IU PO + MCZ inhalation, dose NA | 46 | NA | NA | NA | NA | 0 | ||
| Bodey et al55 | ||||||||
| FLU 400 mg | 41 | 94% AML, 6% ALL | NA | 4.8 | 7.3 | 4.8 | 14.6 | 0 |
| AmB 0.5 mg/kg 3x/wk IV | 36 | 8.3 | 19.4 | 2.7 | 25 | 2.7 | ||
| Wolff et al54 | ||||||||
| FLU 400 mg | 196 | NA | 29/71 | 4.1 | NA | NA | 12.2 | 2.6 |
| AmB 0.2 mg/kg/d IV | 159 | 7.5 | NA | NA | 11.9 | 1.3 | ||
| Winston et al35 | ||||||||
| FLU 400 mg IV od PO | 67 | NA | 100/0 | 25 | NA | NA | NA | 18 |
| d 1–2: ITR 400 mg IV; d 3, ITR 200 IV or ITR 400 sol | 71 | 9 | NA | NA | NA | 9 | ||
| Kern et al79 | ||||||||
| FLU 400 mg + AmB 240 mg PO | 36 | 100% AML relapse | NA | 5.6 | 0 | 53 | 22 | 0 |
| AmB 240 mg PO | 32 | 6.3 | 0 | 34 | 19 | 0 | ||
| Ninane80 | ||||||||
| FLU 3 mg/kg | 245 | 53% AL, 12% NHL/HD, 30% other | NA | 0.8 | NA | NA | 1.2 | NA |
| NYS 0.2 × 106 IU/kg +/− AmB 100 mg/kg | 257 | 1.9 | NA | NA | 2.3 | NA | ||
| Ellis et al81 82 | ||||||||
| FLU 200 mg | 42 | 47% AML, 30% ALL, 8% NHL/HD, 16% | 26/NA | 4.8 | 2.3 | NA | NA | 4.8 |
| CLO 20 mg + NYS 2 × 106IU | 48 | other | 21 | 2.1 | NA | NA | 18.8 | |
| Menichetti et al30 | ||||||||
| FLU 150 mg | 420 | 81% AML, 19% ALL | NA | 2.6 | NA | 16 | 10.5 | 1.2 |
| AmB oral sol 2 g | 400 | 2.5 | NA | 21 | 10 | 0.8 | ||
| Philpott-Howard et al23 and Rozenberg-Arska et al47 | ||||||||
| FLU 50 mg | 256 | 76% AL, 22% other hematol, 2% solid | 21/NA | 2.4 | NA | NA | NA | NA |
| AmB oral sol 2 g or NYS 4 × 106IU | 255 | tumor | 3.5 | NA | NA | NA | NA | |
| Boogaerts et al34 | ||||||||
| ITR oral sol 200 mg | 144 | 66% AML | 9/0 | 5 | 34-151 | 11.8 | 4.1 | |
| AmB caps 1500 mg + NYS 2 × 106IU | 133 | 5 | 4 | 12.8 | 4.5 | |||
| Morgenstern et al31 | ||||||||
| ITR oral sol 5 mg/kg | 288 | 53% AML, 12% ALL, 35% other hematol | NA | 0.3 | 3.1 | NA | 0 | |
| FLU 100 mg | 293 | 2 | 2.4 | NA | 2.4 | |||
| Annaloro et al834-150 | ||||||||
| ITR caps 400 mg + NYS, dose NA | 31 | NA | 35/65 | 12.9 | 3.2 | 6.4 | 0 | |
| FLU 300 mg + NYS, dose NA | 28 | 3.6 | 7.1 | 7.1 | 0 | |||
| FLU 50 mg + NYS, dose NA | 30 | 3.3 | 6.6 | 3.3 | 0 | |||
| Timmers et al65 | ||||||||
| ABCD 2 mg/kg IV | 12 | 25% AML, 8% ALL, 67% other hematol | 0/0 | 0 | NA | NA | 17 | 0 |
| FLU 200 mg | 12 | 0 | NA | NA | 0 | 0 | ||
| Schwartz et al32 | ||||||||
| AmB 20 mg inhalation | 227 | 74% AML, 9% ALL/NHL relapse | 0/17 | 1.8 | 2.2 | 0.4 | 13 | 8 |
| No prophylaxis | 155 | 0.6 | 5.8 | 0.6 | 10 | 7 | ||
| Buchanan et al49 | ||||||||
| NYS 6 × 106 IU PO | 104 | 30% AML, 7% ALL, 29% NHL/HD | NA | NA | NA | NA | NA | NA |
| No prophylaxis | 60 | NA | NA | NA | NA | NA | ||
MCZ indicates miconazole; CLO, clotrimazole; and ABCD, amphotericin B colloidal dispersion. Other abbreviations are defined in Tables 2 and 3 notes.
Annaloro et al83 used a randomized control design and a historic control group; all other authors used a randomized design.
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.