scholarly journals Incidence Density of Invasive Fungal Infections during Primary Antifungal Prophylaxis in Newly Diagnosed Acute Myeloid Leukemia Patients in a Tertiary Cancer Center, 2009 to 2011

2013 ◽  
Vol 58 (2) ◽  
pp. 865-873 ◽  
Author(s):  
Marisa Z. R. Gomes ◽  
Victor E. Mulanovich ◽  
Y. Jiang ◽  
Russell E. Lewis ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Cancer Center ◽  
Remission Induction ◽  
Content Type ◽  
First Remission ◽  
Tertiary Cancer Center ◽  
Acute Myeloid

ABSTRACTAlthough primary antifungal prophylaxis (PAP) is routinely administered in patients with acute myeloid leukemia (AML) during remission-induction and consolidation chemotherapy, the impact of PAP on the incidence of invasive fungal infections (IFIs) is not well described. We retrospectively analyzed the incidence of IFIs in 152 patients with AML who had been admitted to a tertiary cancer center between August 2009 and March 2011 and received PAP within 120 days after first remission-induction chemotherapy. We excluded patients who had undergone stem cell transplantation. Patients received a PAP drug with anti-Aspergillusactivity during 72% (7,660/10,572) of prophylaxis-days. The incidence of documented IFIs (definite or probable according to revised European Organization for Research and Treatment of Cancer [EORTC] criteria) was 2.0/1,000 prophylaxis-days (95% confidence interval [CI], 1.23 to 3.04). IFIs due to molds were more common than IFIs due to yeasts (1.5/1,000 prophylaxis-days versus 0.4/1,000 prophylaxis-days;P= 0.01). Echinocandin-based PAP (8.6 and 7.1/1,000 prophylaxis-days, respectively) was associated with higher rates of documented IFIs than anti-Aspergillusazoles (voriconazole or posaconazole) (2.4 and 1.1/1,000 prophylaxis-days, respectively) at both 42 days (P= 0.03) and 120 days (P< 0.0001) after first remission-induction chemotherapy. The incidence of overall (documented and presumed) IFIs (P< 0.001), documented IFIs (P< 0.01), and empirical antifungal therapies (P< 0.0001) was higher during the first 42 days than after day 42. Despite the broad use of PAP with anti-Aspergillusactivity, IFIs, especially molds, remain a significant cause of morbidity and mortality in AML patients, predominantly during the remission-induction phase. Patients receiving echinocandin-based PAP experienced higher rates of IFIs than did those receiving anti-Aspergillusazoles.

scholarly journals Incidence and Risk Factors for Breakthrough Invasive Mold Infections in Acute Myeloid Leukemia Patients Receiving Remission Induction Chemotherapy

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Heena P Patel ◽  
Anthony J Perissinotti ◽  
Twisha S Patel ◽  
Dale L Bixby ◽  
Vincent D Marshall ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Multivariable Analysis ◽  
Antifungal Prophylaxis ◽  
Remission Induction ◽  
Invasive Mold Infections ◽  
Acute Myeloid

Abstract Background Despite fungal prophylaxis, invasive mold infections (IMIs) are a significant cause of morbidity and mortality in patients with acute myeloid leukemia (AML) receiving remission induction chemotherapy. The choice of antifungal prophylaxis agent remains controversial, especially in the era of novel targeted therapies. We conducted a retrospective case–control study to determine the incidence of fungal infections and to identify risk factors associated with IMI. Methods Adult patients with AML receiving anti-Aspergillus prophylaxis were included to determine the incidence of IMI per 1000 prophylaxis-days. Patients without and with IMI were matched 2:1 based on the day of IMI diagnosis, and multivariable models using logistic regression were constructed to identify risk factors for IMI. Results Of the 162 included patients, 28 patients had a possible (n = 22), probable, or proven (n = 6) diagnosis of IMI. The incidence of proven or probable IMI per 1000 prophylaxis-days was not statistically different between anti-Aspergillus azoles and micafungin (1.6 vs 5.4, P = .11). The duration of prophylaxis with each agent did not predict IMI occurrence on regression analysis. Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.004–1.081; P = .03) and relapsed/refractory AML diagnosis (OR, 4.44; 95% CI, 1.56–12.64; P = .003) were associated with IMI on multivariable analysis. Conclusions In cases that preclude use of anti-Aspergillus azoles for prophylaxis, micafungin 100 mg once daily may be considered; however, in older patients and those with relapsed/refractory disease, diligent monitoring for IMI is required, irrespective of the agent used for antifungal prophylaxis.

scholarly journals 1301. Breakthrough Invasive Fungal Infections based on CYP2C19 Levels in Patients Who were on Voriconazole as Primary Antifungal Prophylaxis in Acute Myeloid Leukemia (AML) undergoing Induction Chemotherapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S665-S665
Author(s):  
Hareesh v Singam ◽  
Yanina Pasikhova ◽  
Rod Quilitz ◽  
John N Greene ◽  
Aliyah Baluch
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Intermediate Metabolizers ◽  
Acute Myeloid

Abstract Background Voriconazole (Vori) is often used for prophylactic anti-fungal therapy in induction chemotherapy for Acute Myeloid Leukemia (AML) patients due to predictable absorption and an extended spectrum antifungal activity. Vori is metabolized predominately by CYP2C19 to metabolites with less antifungal activity. There has been a great interest in understanding CYP2C19 as it significantly affects drug metabolism and pharmacokinetics of numerous drugs including voriconazole. Approximately 39% of patients are genetically predicted to be CYP2C19 ultra-rapid or rapid metabolizers and thus are at an increased risk of breakthrough fungal infection. This study assesses the incidence of breakthrough invasive fungal infections (bIFI) at Moffitt Cancer Center based on CYP2C19 activity. bIFI is defined as new fungal infection while on vori, leading to treatment with liposomal amphotericin B, echinocandin, and/or different triazole. Methods This is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML and received voriconazole as the primary antifungal prophylaxis between July 2017 and June 2019. The patients enrolled were over 18 years old and did not have a history of stem cell transplant or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or received systematic antifungal therapy 30 days prior. CYP2C19 were checked for each of the patients between July 2017 to June 2019 who were undergoing induction chemotherapy for newly diagnosed AML. It was checked within one week of admission. The patients were categorized as rapid metabolizers, intermediate metabolizers, normal metabolizers, and unknown CYP2C19. Results There was an incidence of 20.2% (18/89) bIFI in patients who were on Vori in this study. Of these patients with bIFI infections, 15.7% (3/19) of patients were rapid metabolizers, 14.7% (5/34) were normal metabolizers, 28.5% (4/14) were intermediate metabolizers and 0% (0/3) were poor metabolizers. There were 31% (6/19) breakthrough infections in patients with unknown CYP2C19 characteristics. Conclusion There is no significant statistical difference (p=0.6) among CYP2C19 categories with respect to breakthrough of invasive fungal infections at Moffitt Cancer Center between July 2017 - June 2019. Disclosures Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)

scholarly journals 742. Breakthrough Invasive Fungal Infections with Isavuconazonium Sulfate versus Voriconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia (AML) who Received Induction Chemotherapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S419-S419
Author(s):  
Hareesh v Singam ◽  
Yanina Pasikhova ◽  
Rod Quilitz ◽  
John N Greene ◽  
Aliyah Baluch
Keyword(s):  
Acute Myeloid Leukemia ◽  
Retrospective Analysis ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Cancer Center ◽  
Solid Organ ◽  
Acute Myeloid

Abstract Background Fungal infections in patients with hematologic malignancies are associated with high mortality. Primary antifungal prophylaxis has been shown to be a more effective strategy than treating a documented infection. This retrospective analysis aims to compare the rates of breakthrough invasive fungal infections in patients with acute myeloid leukemia (AML) who received induction chemotherapy and were prescribed voriconazole (Vori) or isavuconazonium (Isv) for primary antifungal prophylaxis. The European Organization for Research and Treatment of Cancer/ Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to categorize incidence of breakthrough invasive fungal infections bIFI into ‘possible’, ‘probable’ or ‘definite’ groups who required treatment with liposomal amphotericin B, echinocandin, and/or different triazole. Methods This is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML. These patients received either Vori or Isv sulfate as the primary antifungal prophylaxis at Moffitt Cancer Center between July 2017 and June 2019. Patients who were over 18 years old and received at least 10 days of uninterrupted primary antifungal prophylaxis with either Vori or Isv sulfate were included in the study. Patients with a history of stem cell or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or who received systematic antifungal, other than fluconazole, therapy within 30 days to induction chemotherapy were excluded. Results 250 patients were screened for the study and out of which 118 patients met the above criteria. There was a 20.2% (18/89) break through rate of fungal infections in the Vori arm and 17.2% (5/29) in the Isv arm. In the Vori arm there were 15 possible bIFIs, 3 probable bIFIs and 0 definite bIFIs. In the Isv arm there are 2 possible bIFIs, 2 probable bIFIs and 1 definite bIFIs. Conclusion There is no significant statistical difference (Using the Fisher Exact test statistic p=1) between the Isv and Vori in patients who received these agents for primary fungal prophylaxis for induction chemotherapy for AML at Moffitt Cancer Center between July 2017 - June 2019. Disclosures Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)

scholarly journals 986. Incidence of Invasive Fungal Infections in Previously Untreated Patients with Acute Myeloid Leukemia Receiving Venetoclax and Azacitadine

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S584-S584
Author(s):  
Tanit Phupitakphol ◽  
Tanner M Johnson ◽  
Diana Abbott ◽  
Jonathan Gutman ◽  
Daniel Pollyea ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Standard Of Care ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Significant Difference ◽  
The Impact ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) is associated with poor prognosis, particularly in elderly patients with co-morbidities. Low-intensity therapies like azacitidine (aza) were the standard of care and were associated with low response rates and limited survival. Combining venetoclax (ven) with aza demonstrated significant improvements in responses and survival compared to aza alone, and represents the new standard of care for this population. However, as a myelosuppressive regimen, infectious complications, especially invasive fungal infections (IFI), are a potential concern. The incidence of IFI and the role for antifungal prophylaxis have not been well defined for newly-diagnosed AML patients receiving ven/aza. Methods We conducted a retrospective cohort review of AML patients treated with ven/aza at the University of Colorado Hospital from January 2014 to August 2020. Duration of therapy was defined as the time from initiation of treatment through one of the following endpoints (1) patient discontinuation, (2) progression of disease, (3) bone marrow transplantation, or (4) death. Four patients with a history of prior IFI were excluded. We assessed the impact of patient age, sex, duration of neutropenia, antifungal prophylaxis, and AML specific risk factors on the incidence of IFI as defined by the European Mycoses Study Group. Results One hundred forty-four AML patients were included in the study. Ten patients received antifungal prophylaxis and none developed IFI (p=0.21). Twenty-five (17%) patients developed IFI: 2 (8%) had proven IFI, 6 (24%) probable IFI, and 17 (68%) possible IFI. Invasive pulmonary aspergillosis represented all 25 cases of proven, probable, and possible IFI. There was a statistically significant association between prolonged neutropenia ( &gt;60 days) and IFI (p=0.007), whereas age, sex, and SWOG classification were not significantly associated with IFI. Conclusion The incidence of IFI in our AML cohorts treated with ven/aza was 17%, lower than that reported at other institutions. Neutropenia &gt; 60 days was significantly associated with IFI in our AML cohort treated with ven/aza. Although we were not powered to determine whether antifungal prophylaxis impacted IFI, there was no significant difference in IFI for patients who received prophylaxis. Disclosures All Authors: No reported disclosures

scholarly journals Posaconazole for the prophylaxis of invasive aspergillosis in acute myeloid leukemia: Is it still useful outside the clinical trial setting?

2020 ◽  
Vol 11 ◽  
pp. 204062072096584
Author(s):  
Tsung-Chih Chen ◽  
Ren Ching Wang ◽  
Yu-Hui Lin ◽  
Kuang-Hsi Chang ◽  
Li-Ya Hung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Invasive Aspergillosis ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Antifungal Prophylaxis ◽  
Remission Induction ◽  
Prophylaxis Group ◽  
Significant Difference ◽  
Acute Myeloid

Background: Posaconazole prophylaxis during remission induction chemotherapy not only decreases the incidence of invasive aspergillosis (IA) but also improves the overall survival rate among patients with acute myeloid leukemia (AML). However, it remains debatable whether this result applies to patients in a real-world setting. Methods: We retrospectively assessed 208 adult patients with newly diagnosed AML who underwent remission induction therapy. These 208 patients were stratified into the posaconazole prophylaxis group ( n = 58) and no antifungal prophylaxis group ( n = 150). Results: Multivariate analyses showed that induction failure significantly increased the risk of proven or probable IA during the first induction chemotherapy [hazard ratio (HR), 10.47; 95% confidence interval (CI), 1.73–63.45; p = 0.011] and the entire course of AML treatment (HR, 4.48; 95% CI, 1.71–11.75; p = 0.002). However, posaconazole prophylaxis did not reduce the risk of IA during the first induction chemotherapy (HR, 1.47; 95% CI, 0.14–15.04; p = 0.746) and during the entire course of AML treatment (HR, 1.09; 95% CI, 0.29–4.09; p = 0.896). Furthermore, there was no significant difference in overall survival between these two groups of patients (514 versus 689 days; p = 0.454). Conclusion: Successful induction remains fundamental to reducing the risk of IA among AML patients undergoing remission induction chemotherapy.

scholarly journals Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents

2019 ◽  
Vol 3 (23) ◽  
pp. 4043-4049 ◽  
Author(s):  
Ibrahim Aldoss ◽  
Sanjeet Dadwal ◽  
Jianying Zhang ◽  
Bernard Tegtmeier ◽  
Matthew Mei ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Hypomethylating Agents ◽  
Key Points ◽  
Acute Myeloid

Key Points The incidence of IFIs during VEN-HMA therapy is low, and the used antifungal prophylaxis approach did not influence the risk of IFIs. The risk of IFIs is higher in nonresponders and those who were treated in the r/r AML setting.

Benefit of Anti-Infectious Prophylaxis in Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Receiving Frontline “Targeted Therapy”.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2858-2858 ◽  
Author(s):  
Nitin Jain ◽  
Gloria N. Mattiuzzi ◽  
Jorge Cortes ◽  
Jennifer Cassat ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Targeted Therapy ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Intensive Chemotherapy ◽  
Standard Chemotherapy ◽  
Antibacterial And Antifungal ◽  
Acute Myeloid

Abstract Background Patients with high risk (HR) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have significant toxicities such as mucositis, protracted neutropenia and severe infections when treated with standard chemotherapy. This had led to the development of ‘less intense’ chemotherapy (targeted therapy, TT). These treatments are expected to produce less toxicities, especially less immunosuppression. Antibiotic and antifungal prophylaxis are routinely given to patients undergoing intensive chemotherapy. It is not clear if the same strategy should be used for patients receiving less intensive chemotherapy. The objective of this study is to evaluate the outcome of patients receiving TT according to the use of antimicrobial prophylaxis. Methods We retrospectively reviewed the medical records of patients with AML and HR MDS that received TT as induction therapy from January 2000 to July 2007 at our institution. Baseline characteristics and antibiotic usage was recorded. All courses of TT received from start of therapy until outcome (response or failure) was assessed were evaluated, and infections or death occurring during any of these courses constituted an event. Results 225 patients received TT [decitabine or azacitidine n = 137 (61%); miscellaneous (tipifarnib, PKC412, imatinib, SAHA, and others) n=88 (39%)] for a total of 583 courses (median course per patient = 2). Median age was 72 years (range 13–89), 60% were male, 95% had Zubroad performance status ≤ 2 and 28% were neutropenic at the start of TT. None of the patients were placed in HEPA-filtered rooms (‘protected environment’) at any time. Each course of therapy was grouped into 1 of 4 groups based on the strategy use for infectious prophylaxis (table 1). Clinically documented infections and FUO were the most frequent type of infection reported in all the groups, followed by bacterial infections. Fungal infections were infrequent (total 5; group 1 = 1; group 2 = 2, group 3 = 2). There was no significant difference in the number of infectious episodes per course between the groups that received both antibacterial and antifungal prophylaxis vs. those who received no prophylaxis (p= 0.984). However, mortality was significantly higher during courses of TT administered without prophylaxis (p= 0.005). Conclusions As opposed to standard chemotherapy, fungal infections are infrequent in the patients treated with TT. Mortality is significantly higher in patients who did not receive any anti-microbial prophylaxis. The use of antibacterial and antifungal prophylaxis should be considered in patients receiving TT. Table 1: Groups based on antimicrobial strategy Strategy Strategy No. of courses No. of infectious episodes (%) No. of death (%) * p=0.984; # p=0.005 No prophylaxis 202 45 (22%) * 12 (5.94%) # Both bacterial and fungal prophylaxis 171 38 (18%) * 1 (0.58%) # Only bacterial prophylaxis 206 31 (15%) 6 (2.91%) Only fungal prophylaxis 4 0 (0%) 0 (0%)

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