Acute Myelogenous Leukemia Patients Are at Low Risk for Invasive Fungal Infections after High-Dose Cytarabine Consolidations and Thus Do Not Require Prophylaxis

Abstract

We evaluated the frequency of invasive fungal infections (IFI), the frequency of empirical antifungal use (EAFU), and the efficacy of fluconazole prophylaxis on IFI and EAFU after high-dose cytarabine (HiDAC) consolidations. Twenty-seven acute myelogenous leukemia patients in their first complete remission received 76 cycles of HiDAC (median cycle: n = 3). Fluconazole prophylaxis was administered following 44 cycles (fluconazole group) and not given in 32 cycles (control group). IFI (2 episodes) + EAFU (11 episodes) was observed in 13 of 76 cycles (17%); there was no difference between the fluconazole group and the control group (p = 0.469). Neutropenia duration was <13 days in 89% of the 76 cycles and was similar in the fluconazole and control groups (p = 0.845). Neutropenic fever was observed in 34 of the 76 cycles (45%) and was similar in the fluconazole group and the control group (p = 0.43). Although HiDAC cycle 1 was associated with a shorter neutropenia duration, there was no association between HiDAC cycle numbers and neutropenic fever or IFI + EAFU. HiDAC consolidations resulted in a high rate of neutropenic fever, the lack of an appreciable benefit from EAFU, and rare IFI. Most likely because of the low incidence of IFI, use of fluconazole or another antifungal is not warranted in this setting.

Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period

“…The choice of fluconazole/itraconazole as comparators to voriconazole/posaconazole was based on clinical trial experience. 6 That consolidation chemotherapy is low risk for IFD (affecting 3 of 27 patients) compared to post-induction aplasia 1,16,22 suggests review of our universal policy of broad-spectrum prophylaxis may be warranted.…”

Does high‐dose cytarabine cause cumulative toxicity in patients undergoing consolidation therapy for acute myeloid leukemia?

“…Although the studies we discuss here have significant differences in patient size (small or large), center number (single or multicenter), type of study (prospective or retrospective), and geographical place (Europe, USA, or Japan), these study results are remarkably consistent [4][5][6][7][8]. No study reported increased mortality by increased number of HiDAC cycles.…”

“…The number of platelet and red blood cell transfusions [5,7] and duration of thrombocytopenia [7] remained stable throughout the HiDAC cycles [5,7]. Documented fungal infections [8], empirical intravenous antifungal use [8], duration of antibiotic use [7], and the frequency of pneumonia [5] were similar between HiDAC cycles. No accumulated central nervous system, hepatic, or renal toxicity reported during HiDAC cycles [5,7].…”

“…No study reported increased mortality by increased number of HiDAC cycles. The frequency of neutropenic fever, the duration of neutropenia, and neutropenic fever were not increased by the HiDAC cycle number [5,7,8]. Rather, it has been described that the numbers of functionally active neutrophils (exhibiting anti-bacterial effects) often survive until day 10 or even 12 in HiDAC-treated patients [9].…”

Lethal small bowel necrosis due to aspergillosis during acute promyelocytic leukemia induction

“…The infectious diseases society of America (IDSA) recommends antibiotic prophylaxis using a fluoroquinolone in high-risk patients, i.e., those leukemia patients with expected neutropenia >7 days [7]. Consistently, AML patients who have short neutropenia duration (e.g., post-consolidation) do not benefit from antifungal prophylaxis [8]. These guidelines recommend antifungal prophylaxis against Candida infections in patients undergoing intensive remission-induction or salvage-induction for acute leukemia, and antiviral prophylaxis for herpes simplex virus (HSV) in patients undergoing leukemia induction therapy.…”