Antifungal Prophylaxis (AFP) for Patients (Pts) with Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS) Undergoing Intensive Chemotherapy: An Experience with 730 Pts.
Authors: Mattiuzzi Gloria , Kantarjian Hagop , Ho Jennifer , Garcia-Manero Guillermo , Cortes Jorge 
Published: October 2019

Abstract
Abstract 3102
Poster Board III-39
Despite the advances in the development of antifungal agents, invasive fungal infections (IFI) remain a significant threat to patients with hematologic malignancies. The importance of early intervention for patients at high-risk for IFI has been widely discussed in several publications; however, the question of whether an early intervention such as prophylaxis is better than empiric or pre-emptive treatment still remains unanswered. Antifungal prophylaxis continues to be routinely used at MDACC for AML and HR-MDS patients. An ideal AFP regimen should be effective, safe, and uncomplicated for the patients. In the search of this ideal regimen, we have explored several options, including different type of drugs and various delivery schedules. Hereby, we report our experience since September 1997 to August 2009 with 730 AML and HR-MDS patients who received AFP for intensive chemotherapy. Proven IFI were defined as per the EORTC criteria. The following regimens were studied: Amphotericin B Lipid Complex (ABLC): 2.5 mg/kg IV three times/week; Liposomal Amphotericin B (AMBI 3TIW): 3 mg/kg IV three times/week; Fluconazole 400 mg (tab) /d + Itraconazole:200 mg (caps) /d (F + I); IV Itraconazole (IV ITRA):200 mg BID X 2 d, then 200 mg IV/d; Caspofungin (CASPO):50 mg IV /d; Voriconazole (IV VORI):400 mg IV BID x 2 d, then 300 mg IV BID; Liposomal Amphotericin B (AMBI 9/W): 9 mg/kg IV once per week; and Voriconazole (PO VORI ): 400 mg BID PO x 1 day, followed by 200 mg PO BID. Patients received ABLC, IV ITRA, F+I, AMBI 3TIW and CASPO since day 1 of IC until IC response was assessed. Pt on IV VORI, AMBI 3TIW and PO VORI started AFP within 24 hours after the last dose of IC until IC response was assessed. There were no significant differences among the pts in the 8 regimens with regards to age, gender, diagnosis, cytogenetics, performance status, presence of no fungal infection at start IC and stayed in protected environment. Table 1 shows our results. Although none of the pts receiving Voriconazole (IV or PO) developed proven IFI, all comparisons of efficacy among the AFP regimens were not significant (p= 0.291). None of the patients on AMBI 3TIW and either VORI had mold infections. There was a significant difference in the number of side effects among the 8 groups (p = 0.03). CASPO and PO VORI were the less toxic regimens. In addition, PO VORI was significantly less toxic than IV VORI (p=0.031).
ABLC (N=131) AMBI 3TIW (N=69) F+I (N=67) IV ITRA (N=225) CASPO (N=106) VORI IV (N=61) AMBI 9/w (N=27) PO VORI (N=38) Breakthrough proven IFI n (%) 7(5) 3(4) 3(5) 17(8) 7(7) 0 2 (7) 0 –Yeast 2 3 1 11 3 0 1 0 –Mold 5 0 2 6 4 0 1 0 Drug-related side effects (%) 18 14 7 10 4 21 12 5
We conclude that PO VORI is safe, efficacious and easy to administer to the patients for the prevention of IFI in pts with AML and HR-MDS undergoing IC. CASPO is a safe alternative.

Disclosures
No relevant conflicts of interest to declare.