scholarly journals Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

2014 ◽  
Vol 58 (10) ◽  
pp. 5758-5765 ◽  
Author(s):  
Rafael F. Duarte ◽  
Javier López-Jiménez ◽  
Oliver A. Cornely ◽  
Michel Laverdiere ◽  
David Helfgott ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Average Concentration ◽  
Myelogenous Leukemia ◽  
Time Curve ◽  
Once Daily ◽  
High Risk Patients ◽  
Exposure Target ◽  
Risk Patients ◽  
Neutropenic Patients

ABSTRACTPosaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n= 20) and 300 mg posaconazole once daily (n= 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered atClinicalTrials.govunder registration no. NCT01777763.)

scholarly journals 1701. Differences in Diagnostic Performance of β-d-Glucan Testing in Patients with Varying Degrees of Susceptibility to Invasive Fungal Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S623-S623
Author(s):  
Eliel Nham ◽  
Si-Ho Kim ◽  
Hyunjoo Lee ◽  
Jae-Hoon Ko ◽  
Kyungmin Huh ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Diagnostic Performance ◽  
Fungal Infections ◽  
Pneumocystis Pneumonia ◽  
Host Factors ◽  
European Organization ◽  
High Risk Patients ◽  
Risk Patients ◽  
Group A

Abstract Background Usefulness of β-d-glucan (BDG) testing in high-risk patients for invasive fungal infection (IFI) diagnosis has been well demonstrated. However, data on its usefulness in patients without risk factors are limited. We evaluated differences in the diagnostic performance of BDG testing in patients with varying degrees of susceptibility to IFI. Methods From April 2017 to May 2018, all consecutive patients (≥18year-old) who were performed BDG testing (Beijing Gold Mountainriver Tech) were enrolled. Patients were classified into three groups: Group A for patients with host factors defined by 2008 European Organization for Research and Treatment of Cancer-Mycoses Study Group diagnostic (EORTC-MSG) criteria, Group B for patients with malignancy receiving recent chemotherapy within 1 month without host factors, and Group C for others. Cases of proven and probable IFI defined by EORTC-MSG criteria, Pneumocystis pneumonia and all fungemia were considered as true IFIs. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were calculated with a cut-off value for positivity ≥80 pg/mL. Results Among 473 eligible patients, 190, 142, and 141 patients were classified into group A, B, and C, respectively. Rates of true IFI were significantly different in each group (57/190, 19/142, and 10/141 in each group, P < 0.001). Sensitivities were 0.83, 0.68, and 0.70 and specificities were 0.62, 0.59, and 0.63 in group A, B, and C, respectively. PPVs were considerably different among three groups (PPV for 0.48, 0.20, and 0.12; NPV for 0.89, 0.92 and 0.97 in each group, respectively). Conclusion The BDG test is a useful assay for IFI diagnosis; however, the clinical interpretation should be different by patient risks. Whereas BDG testing could be considered as a tool for predicting IFI in high-risk patients, it only could be a tool for excluding IFI in patient without risk factors. Disclosures All authors: No reported disclosures.

Is Antifungal Prophylaxis Useful In Stem Cell Transplantation (SCT) During Hospitalization?.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4541-4541
Author(s):  
Giuseppe Irrera ◽  
Messina Giuseppe ◽  
Giuseppe Console ◽  
Massimo Martino ◽  
Cuzzola Maria ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Mucosal Damage ◽  
Invasive Disease ◽  
Secondary Prophylaxis ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
High Risk Patients ◽  
Risk Patients

Abstract Abstract 4541 Introduction: Limited data demonstrate to what extent preventing fungal exposures is effective in preventing infection and disease. Further studies are needed to determine the optimal duration of fluconazole prophylaxis in allogeneic recipients to prevent invasive disease with fluconazole-susceptible Candida species during neutropenia. Oral, nonabsorbable antifungal drugs might reduce superficial colonization and control local mucosal candidiasis, but have not been demonstrated to reduce invasive candidiasis. Anti-fungal prophylaxis is recommended in a subpopulation of autologous recipients with underlying hematologic malignancies with prolonged neutropenia and mucosal damage. Methods: This is a retrospective study of 1007 SCT performed in our center between 1992 and 2009 in 809 consecutive patients, irrespective of diagnosis. HEPA filter and environmental monitoring (air, water, surfaces) are attributes of our transplant center. Results: The main characteristics of the patients are reported in Table 1. Systemic prophylaxis was used according to the guidelines (Table 2): fluconazole in the nineties, then itraconazole and from 2004 was either abolished or substituted with non-adsorbable prophylaxis in transplants with standard risk. Secondary prophylaxis was prescribed for high risk patients (with infectious fungal history, suggestive iconography, positive fungal biomarker). In 17 years our Center has never been colonized by mould. Only 3 probable aspergillosis infections and 4 proven fungal infections (fusarium, mucor and 2 aspergillosis) were diagnosed, all in allogeneic patients (2 haplotipical, 1 singenic, 1 sibiling, 1 MUD and 2 mismatched), resulting in death in all cases. No infection was documented in autologous setting, while the infection rate in allogenic setting was 3.6% with an incidence rate of 1.1 infection per 10000 transplants/year. These results are significantly lower than published reports. Conclusion: Systemic antifungal prophylaxis should not be performed in autologous SCT patients. The abuse of systemic prophylaxis targeting yeasts has influenced the change of epidemiology in the transplant setting with prevalence of mould infections. The identification of high risk patients is useful to select patients for systemic antifungal or secondary prophylaxis to reducing overtreatment, incidence of resistant strains and costs. Disclosures: No relevant conflicts of interest to declare.

Comorbidity and Outcomes for Patients Over Age 65 Years Treated with Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndrome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2032-2032 ◽  
Author(s):  
Henry J. Conter ◽  
Nhu-Nhu Nguyen ◽  
Gabriela Rondon ◽  
Julianne Chen ◽  
Elizabeth J Shpall ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cumulative Incidence ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myelogenous ◽  
Related Mortality

Abstract Abstract 2032 Background: Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) preferentially afflict patients 65 years of age and older. Patients in this age group are likely to have underlying comorbid conditions. These comorbidities affect treatment planning decisions and clinical outcomes. Here we report comorbidity-stratified outcomes of patients older than 64 treated at MD Anderson Cancer Center from 1996 until 2011, inclusive, treated with allogeneic stem cell transplant (ASCT). Methods: 182 patients older than 64 received an ASCT for AML (n=143) or MDS (n=39). Patient charts were reviewed and comorbidity data abstracted using a standardized form. Burden of comorbidity was assessed using the Hematopoetic Stem Cell Transplant-Specific Comorbidity Index (HSCT-CI). Low-risk, intermediate-risk, and high-risk patients were categorised at 0, 1–2, and >=3 points as per the HSCT-CI. 157 patients were evaluable for pre-transplant comorbidity. Outcomes of interest were cumulative incidence of transplant-related mortality (TRM), cumulative incidence of relapse-related mortality (RRM), incidence of acute and chronic graft-versus-host disease (GVHD), and overall survival (OS). These were estimated from the date of transplantation. Results: The median age of transplanted patients was 67 (range 65–79), and 37 patients age 70 and older were treated. The majority of patients were intermediate-risk and high-risk patients (table), 9 patients had HSCT-CI scores of >=5. Median follow-up for alive patients was 12.6 months (n=63; range 0–118). Cumulative incidence of TRM was 6% at 100 days, 14% at 1 year, 23% at 2 years, and 36% at 5 years (figure). Cumulative incidence of RRM was 36% at 1 year, 42% at 2 years, and 47% at 5 years. HSCT-CI did not independently predict for either TRM or RRM (log-rank test p=0.95). The incidence of grade III and IV acute GVHD was 10% of all patients. The cumulative incidence of chronic GVHD was 25% at 1 year, 27% at 2 years, and 30% at 5 years, with no association between GVHD and HSCT-CI comorbidity. Conclusion: ASCT is a curative option for selected patients over age 64. HSCT-CI did not predict TRM or survival on this cohort of high-risk patients. Disease relapse was of greater concern than TRM, and so novel approaches to relapse prevention are needed. Disclosures: No relevant conflicts of interest to declare.

Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia.

1997 ◽  
Vol 15 (1) ◽  
pp. 44-51 ◽  
Author(s):  
K Seiter ◽  
E J Feldman ◽  
H D Halicka ◽  
F Traganos ◽  
Z Darzynkiewicz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Acute Leukemia ◽  
S Phase ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
Laboratory Evaluation ◽  
Apoptotic Cells ◽  
High Risk Patients ◽  
Risk Patients

PURPOSE To determine the maximal-tolerated dose (MTD) of topotecan with cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in these patients. PATIENTS AND METHODS Fifty-three patients with acute leukemia not responsive to standard therapy were treated at eight dose levels of topotecan (2.5 mg/m2/d to 7.75 mg/m2/d). Topotecan was given as a 30-minute infusion daily with cytarabine 1 g/m2/d, both for 5 days. Using a flow-cytometric technique, the percent apoptotic cells in blood and bone marrow samples was determined, and the cell cycle distribution of the leukemic cells studied. RESULTS Oropharyngeal mucositis was dose-limiting. The MTD of topotecan was 4.75 mg/m2/d for 5 days in high-risk patients and 7.0 mg/m2/d for 5 days in low-risk patients. The mean percent apoptotic cells in the peripheral blood reached a peak of 18.8%, a median of 48 hours following the first dose of topotecan. Patients with higher S-phase fractions, either before treatment or following cytarabine, were more likely to achieve bone marrow aplasia than those with lower S-phase fractions (P = .01 and P < .05, respectively). Clinical responses were seen in four of 39 patients with acute myelogenous leukemia (AML; of whom 32 had received prior high-dose cytarabine), three of six with acute lymphoblastic leukemia (ALL), and one of eight with chronic myelogenous leukemia in blast phase (CML-BP). CONCLUSION The recommended phase II dose of topotecan with intermediate-dose cytarabine is 4.75 mg/m2/d for high-risk patients and 7.0 mg/m2/d for low-risk patients. The percentage of cells in S phase was important in determining response to treatment.

Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients

2009 ◽  
Vol 66 (19) ◽  
pp. 1711-1717 ◽  
Author(s):  
Joseph Menzin ◽  
Juliana L. Meyers ◽  
Mark Friedman ◽  
John R. Perfect ◽  
Amelia A. Langston ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
High Risk Patients ◽  
Risk Patients ◽  
Length Of Hospitalization

scholarly journals Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High Risk for Fungal Infections

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Alan Chin ◽  
Steven A. Pergam ◽  
David N. Fredricks ◽  
Andrew N. Hoofnagle ◽  
Kelsey K. Baker ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Medical Condition ◽  
Solid Organ Transplantation ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
High Risk Patients ◽  
Delayed Release ◽  
Risk Patients

ABSTRACT The purpose of our study was to determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed-release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs) and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels. A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that had received PCZ and obtained PCZ serum levels for either treatment or prophylaxis between 1 August 2014 and 31 August 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell transplantation (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 μg/liter and ≥1,000 μg/liter were considered appropriate for prophylaxis and treatment, respectively. The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients had PCZ serum levels of ≥700 μg/liter regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels of ≥1,000 μg/liter. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight of ≥90 kg, a diarrhea grade of ≥2, a mucositis grade of ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment than in those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough IFIs, one of which had a subtherapeutic level. We concluded that the use of PCZ DRT provided adequate concentrations in only 70% of our patients and that recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.

Are patients with high-risk polycythemia vera (PV) receiving cytoreductive medications? A retrospective analysis of real-world data.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18031-e18031
Author(s):  
Dilan Paranagama ◽  
Jingbo Yu ◽  
Philomena Colucci ◽  
Kristin Evans ◽  
Machaon Bonafede ◽  
...  
Keyword(s):  
High Risk ◽  
Current Treatment ◽  
Treatment Recommendations ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
Real World Data ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myelogenous ◽  
History Of

e18031 Background: Risk-adapted therapy in PV is aimed at preventing thrombotic events (TE). Under current treatment recommendations (including European LeukemiaNet), high-risk patients (age ≥ 60 y and/or history of TE) should be managed with cytoreductive medications in addition to phlebotomy and low-dose aspirin. The objective of this study was to describe cytoreductive medication usage in patients with high-risk PV. Methods: Retrospective claims from the Truven Health MarketScan Database were analyzed. Inclusion criteria were ≥ 2 non-diagnostic claims for PV >30 days apart, age ≥ 18 y, continuous enrollment during pre-index (1/1/2012–12/31/2012), and continuous enrollment through or death during the study period (1/1/2013–12/31/2014). Patients with claims for myelodysplastic syndrome, myelofibrosis, acute myelogenous leukemia, or secondary polycythemia were excluded. Descriptive statistics were used. Results: The study included 2856 patients. Mean (SD) age was 62.5 (13.5) y, 65.9% of patients were male, and 63.8% were high-risk. Comorbid conditions of interest were reported more frequently in high-risk patients than low-risk patients: hypertension (65.0% vs 43.1%), diabetes (21.7% vs 10.1%), and congestive heart failure (6.6% vs 0.6%). In low- and high-risk patients, the most commonly used cytoreductive medications were hydroxyurea (93.6%), anagrelide (7.6%), and interferon (2.4%). Low-risk patients received cytoreductive medications less often than high-risk patients (Table). However, only 42% of the high-risk patients received treatment with a cytoreductive medication by the end of the study. Conclusions: Despite higher cardiovascular risk and treatment recommendations, less than half of the high-risk PV patients received cytoreductive medications. Furthermore, less than a third of younger patients with a prior TE received cytoreductive medications. [Table: see text]

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