Abstract

Invasive fungal infections (IFI) are a frequent cause of morbidity and death in pts with AML and high-risk myelodysplastic syndrome (HR-MDS). Because early diagnosis of IFI is difficult, antifungal prophylaxis (AFP) including mold-active agents has become an important strategy to reduce morbidity and mortality in this patient population and is routinely used at MDACC for AML and HR-MDS pts undergoing RIC. We retrospectively compared the efficacy and safety of 6 AFP regimens (Sept 97- July 04) among 659 evaluable pts with newly diagnosed AML and HR-MDS who received RIC and had been enrolled in our prospective AFP trials. See regimens listed in Table below. There were no significant differences among the 6 regimens with regard to key baseline characteristics (age, gender, diagnosis, cytogenetics, type of RIC, Zubrod PS, WBC count, non-fungal infection and protected environment) and median days of AFP. 37 pts (5.6%) developed IFI (yeast 3 %; mold 2.6%). No mold infections were observed among pts randomized to AMBI or VORI. With the exception of VORI, which was significantly more effective than IV ITRA (p =0.03), all comparisons of efficacy among the AFP regimens were not significant. Drug discontinuation was the highest with IV VORI (21%) and ABLC (18%). VORI was more toxic than IV ITRA, Caspo, and F+I (p=0.023, 0.001 and 0.031 respectively). VORI toxicity was reversible and consisted of visual and/or auditory hallucinations and elevation in serum bilirubin. There was a trend toward developing VORI toxicity if baseline bilirubin levels were elevated (OR=4.9; p=0.10).

We conclude that the rate of IFI in AML and HR-MDS pts undergoing RIC given mold-active AFP is 5.6 %. VORI and AMBI effectively prevented mold infections. VORI was more effective that IV ITRA but was associated with a high rate of reversible drug-related adverse events.

 ABLC (n=131) AMBI (n=69) F+I (n=67) IV ITRA (n=225) CASPO (n=106) VORI (n=61) 
ABLC: Amphotericin B Lipid Complex: 2.5 mg/kg IV three times/week; 
AMBI: Liposomal Amphotericin B: 3 mg/kg IV three times/week; 
F+I: Fluconazole: 400 mg (tab)/d + Itraconazole: 200 mg (caps)/d; 
IV ITRA: IV itraconazole: 200 mg BID X 2 d, then 200 mg IV/d; 
CASPO: Caspofungin: 50 mg IV/d; 
VORI: Voriconazole: 400 mg IV BID x 2 d, then 300 mg IV BID. 
Median age, years (range) 65(21–87) 63(36–83) 57(19–84) 62(17–89) 65(22–82) 59(23–79) 
Zubrod ≤ 2 (%) 127(97) 69(100) 65(97) 214(95) 101(95) 61(100) 
Median days AFP (range) 17(3–32) 14(3–28) 16(3–44) 20(3–41) 21(3–38) 21(3–34) 
Breakthrough IFI (%) 7(5) 3(4) 3(5) 17(8) 7(7) 0 
    Yeast (%) 2(2) 3(4) 1(1) 11(5) 3(3) 0 
    Mold (%) 5(4) 0 2(3) 6(3) 4(4) 0 
Drug-related AFP DC (%) 24(1810(14) 5(7) 23(10) 4(4) 13(21
 ABLC (n=131) AMBI (n=69) F+I (n=67) IV ITRA (n=225) CASPO (n=106) VORI (n=61) 
ABLC: Amphotericin B Lipid Complex: 2.5 mg/kg IV three times/week; 
AMBI: Liposomal Amphotericin B: 3 mg/kg IV three times/week; 
F+I: Fluconazole: 400 mg (tab)/d + Itraconazole: 200 mg (caps)/d; 
IV ITRA: IV itraconazole: 200 mg BID X 2 d, then 200 mg IV/d; 
CASPO: Caspofungin: 50 mg IV/d; 
VORI: Voriconazole: 400 mg IV BID x 2 d, then 300 mg IV BID. 
Median age, years (range) 65(21–87) 63(36–83) 57(19–84) 62(17–89) 65(22–82) 59(23–79) 
Zubrod ≤ 2 (%) 127(97) 69(100) 65(97) 214(95) 101(95) 61(100) 
Median days AFP (range) 17(3–32) 14(3–28) 16(3–44) 20(3–41) 21(3–38) 21(3–34) 
Breakthrough IFI (%) 7(5) 3(4) 3(5) 17(8) 7(7) 0 
    Yeast (%) 2(2) 3(4) 1(1) 11(5) 3(3) 0 
    Mold (%) 5(4) 0 2(3) 6(3) 4(4) 0 
Drug-related AFP DC (%) 24(1810(14) 5(7) 23(10) 4(4) 13(21

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