scholarly journals Galactomannan Does Not Precede Major Signs on a Pulmonary Computerized Tomographic Scan Suggestive of Invasive Aspergillosis in Patients with Hematological Malignancies

2005 ◽  
Vol 41 (8) ◽  
pp. 1143-1149 ◽  
Author(s):  
M. Weisser ◽  
C. Rausch ◽  
A. Droll ◽  
M. Simcock ◽  
P. Sendi ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Hematological Malignancies

Liposomal Amphotericin B (L-AMB) as Initial Therapy for Invasive Filamentous Fungal Infections (IFFI): A Randomized, Prospective Trial of a High Loading Regimen vs. Standard Dosing (AmBiLoad Trial).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3222-3222 ◽  
Author(s):  
Oliver A. Cornely ◽  
Johan Maertens ◽  
Mark Bresnik ◽  
Raoul Herbrecht
Keyword(s):  
Drug Treatment ◽  
Invasive Aspergillosis ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
Prospective Trial ◽  
Study Drug ◽  
Initial Therapy ◽  
High Loading ◽  
Double Blind Study ◽  
Overall Response

Abstract Background: L-AMB exhibits non-linear pharmacokinetics, with maximal values for Cmax and AUC achieved at a dose of 10 mg/kg/d. Maximal tolerated dose is >15 mg/kg/d. In animal models improved efficacy has been demonstrated with higher doses of L-AMB, but comparative clinical data for efficacy of higher than standard doses of L-AMB are lacking. A randomized, double blind study was performed to compare the efficacy and safety of a high loading dose regimen (HD) to standard dosing (SD) as initial therapy of IFFI. Methods: Patients with proven or probable IFFI by modified EORTC/MSG criteria were randomized to receive L-AMB 3 or 10 mg/kg/d x14d, then 3 mg/kg/d until investigator-defined end of study drug treatment (EOT). Study drug was blinded for the first 14 days of treatment. The primary endpoint was favorable overall response (FOR) assessed at EOT. FOR=complete responses + partial responses. Survival was followed up to 12 wks. An independent Data Review Board (DRB) confirmed all IFFI diagnoses and response assessments. Results: 201 patients with DRB confirmed IFFI diagnoses comprised the MITT population. 107 received SD, 94 HD. Groups were well matched in terms of risk factors. 93% of patients in each group had underlying hematological malignancies. 16% of SD and 19% of HD patients had allogeneic SCT. Neutropenia was present at baseline in 73% of patients overall, and persisted through EOT in 42%. Invasive aspergillosis (IA) accounted for 97% of cases. Median duration of study drug treatment was SD 15d (range 1–60d) and HD 14d (range 1–57d). FOR at EOT was 50% for SD vs. 46% for HD (p= NS). No significant differences in FOR by treatment group were seen for the subsets of IA, allo-SCT, neutropenia subsets, or site of IFFI. Survival at 12 wks was 72% SD vs. 59% HD (p= NS). Nephrotoxicity (serum creatinine ≥ 2x baseline) occurred in 14% SD vs. 31% HD (p<.01). Grade 3 or greater hypokalemia (K+<3.0 mmol/L) developed in 16% SD vs. 30% HD (p<.02), but no difference was found in grade 4 hypokalemia (K+ ≤ 2.5 mmol/L) 3% SD vs. 4% HD (p= NS). Conclusions: In a population of highly immunocompromised patients (93% with underlying hematological malignancies, 73% with neutropenia at study entry), L-AMB as initial treatment of invasive aspergillosis and other filamentous fungal infections at a standard dose of 3 mg/kg/d had an overall favorable response rate of 50% and a 12 wk survival rate of 72%. L-AMB given as a high loading regimen of 10 mg/kg/d x14d did not demonstrate any benefit in overall response or survival, and was associated with higher rates of nephrotoxicity and hypokalemia.

Clinical Outcome of Aspergillus-Specific Cytotoxic T Lymphocytes for Refractory Invasive Aspergillosis in Patients with Hematological Malignancies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2215-2215 ◽  
Author(s):  
Tong Wu ◽  
Chun-Rong Tong ◽  
Xing-Yu Cao ◽  
Jing-Bo Wang ◽  
Lung-Ji Chang ◽  
...  
Keyword(s):  
Clinical Study ◽  
T Lymphocytes ◽  
Invasive Aspergillosis ◽  
Cytotoxic T Lymphocytes ◽  
Hematological Malignancies ◽  
Antifungal Agents ◽  
Cytotoxic T Lymphocyte ◽  
Complete Response ◽  
Pilot Clinical Study ◽  
Poor Tolerance

Abstract Invasive aspergillosis has high mortality in patients with hematological malignancies after chemotherapy or allogeneic stem cell transplantation (SCT) due to usually low response rate to current antifungal agents and relatively poor tolerance to the toxicities of the antifungal medicines. In this pilot clinical study, we explore to manage the patients with refractory invasive aspergillosis with aspergillus-specific cytotoxic T lymphocytes (aspergillus CTL). Ten patients who were either no longer response to antifungal medicines or have to stop antifungal agents due to severe toxicities were included in this clinical study. Diagnosis are ALL (2 cases), AML (5 cases), and CML (3 cases). The median age was 37 (10 to 62) years old. Seven of them received allogeneic SCT (unrelated 3 cases, haploidentical 3 cases, identical sibling 1 case), and 3 patients were after chemotherapy. Aspergillus CTLs were either donor origin (5 cases) or patient origin (5 cases) if original donor was not available. Patients received 1 to 3 infusions of aspergillus CTLs. The median CTLs infused were 3.61 (0.28–40.00) x 105/kg. No infusion-related reactions were noted. No pre-existed graft-versus-host disease deteriorated. With aspergillus CTL therapy, one of them (10%) achieved complete response, 6 patients (60%) improved significantly, 1 case was stable, and 2 patients became worse. Our preliminary data has shown that aspergillus-specific cytotoxic T lymphocyte is a safe and promising mean to manage refractory invasive aspergillosis in patients with hematological malignancies.

scholarly journals Impact of galactomannan testing on the prevalence of invasive aspergillosis in patients with hematological malignancies

2012 ◽  
Vol 50 (3) ◽  
pp. 266-269 ◽  
Author(s):  
Martin Hoenigl ◽  
Helmut J. F. Salzer ◽  
Reinhard B. Raggam ◽  
Thomas Valentin ◽  
Angelika Rohn ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Hematological Malignancies

scholarly journals 2268. Clinical Implications of Azole-Resistant vs. Azole-Susceptible Invasive Aspergillosis in Hematological Malignancy (CLARITY): A Multicenter Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S776-S776
Author(s):  
Danila Seidel ◽  
Oliver Cornely ◽  
Dorothee Arenz ◽  
Jacques Meis ◽  
Jörg Vehreschild ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Hematological Malignancies ◽  
Hematological Malignancy ◽  
Underlying Disease ◽  
Clinical Implications ◽  
Central Laboratory ◽  
Resistant Group ◽  
Study Completion ◽  
Worldwide Network ◽  
Susceptible Group

Abstract Background In recent years, survival of patients with invasive aspergillosis (IA) has improved mainly due to availability of extended spectrum triazoles. These advances are jeopardized by the emergence of azole resistance in Aspergillus fumigatus, the most common causative pathogen of IA. Despite several studies suggesting high probability of azole treatment failure in patients with azole-resistant isolates, the clinical implications of azole-resistant IA compared with azole-susceptible IA remain unclear. Methods In patients with hematological malignancies, cases of proven or probable IA (EORTC/MSG 2008) caused by A. fumigatus are registered. Retrospective data are documented, comprising demographics, diagnosis, treatment, response and outcome. Participating sites provided susceptibility results or isolates. Provided isolates were analyzed in a central laboratory. Results Since January 2018, 51 sites in 15 countries worldwide enrolled 154 cases diagnosed with IA between 2010 and 2019, of which 23 (14.9%) had azole-resistant IA. Of 44 cases, the respective clinical fungal isolate was analyzed in the central laboratory. A mixed fungal infection was reported for 34 patients (22.1%), 1 (2.9%) in the azole-resistant group; most were related to non-fumigatus Aspergillus species (n = 12, 35.3%) and non-Aspergillus molds (n = 10, 29.4). Most patients were male (n = 98, 63.6%); 19 (82.6%) in the azole-resistant group, 79 (60.3%) in the azole-susceptible group. Age was documented in categories instead of the exact age. Median age group was 50–69 years in both groups (ranging from 7–11 to 70–89 years for azole-resistant cases, 1–12 months to 70–89 years for azole-susceptible cases). Underlying disease and survival are shown in the table. Conclusion A worldwide network of investigators contributes to the CLARITY registry study. Completion of recruitment and subsequent data analysis are planned for 2019. Further sites may be added if azole-resistant cases are encountered. Disclosures All authors: No reported disclosures.

scholarly journals Comparison of PCR-ELISA and Real-Time PCR for invasive aspergillosis diagnosis in patients with hematological malignancies

2010 ◽  
pp. 1-6 ◽  
Author(s):  
Inès Hadrich ◽  
Charles Mary ◽  
Fattouma Makni ◽  
Moez Elloumi ◽  
Henri Dumon ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Real Time ◽  
Real Time Pcr ◽  
Hematological Malignancies

scholarly journals Role of Aspergillus Galactomannan Antigen Test for the Screening of Invasive Aspergillosis in Patients with Hematological Malignancies

2019 ◽  
pp. 1-10
Author(s):  
Eman H. Salem ◽  
Asmaa M. Elbrolosy ◽  
Samah M. Awad ◽  
Suzan A. Alhassanin ◽  
Amira I. Aldesoky ◽  
...  
Keyword(s):  
High Risk ◽  
Blood Culture ◽  
Invasive Aspergillosis ◽  
Predictive Value ◽  
Hematological Malignancies ◽  
Serological Detection ◽  
Isolation And Identification ◽  
European Organization ◽  
Elisa Testing ◽  
Galactomannan Antigen

Background: Invasive aspergillosis (IA) is a leading cause of death among immunocompromised patients, particularly those with hematological malignancies. The use of galactomannan (GM) antigen as a biological marker for screening of IA in high-risk patients is attractive and non-invasive tool that detect evidence of IA prior to the appearance of clinical manifestations. Objectives: The aim of this study was to compare the diagnostic value of the conventional blood culture technique to the serological detection of GM antigen using ELISA for screening of IA in neutropenic patients with hematological malignancies. Methods: Forty patients with haematological malignancies from those admitted to the Clinical Oncology Department of Menoufia University Hospitals (MUH) were enrolled and classified to have either proven (5/40; 12.5%), probable (10/40; 25%) or possible (25/40; 62.5%) invasive aspergillosis based on the clinical criteria provided by the European Organization for research and treatment of Cancer (EORTC) and Mycoses Study Group (MSG). Blood samples were collected from all participants and subjected to conventional blood culture for isolation and identification of Aspergillus spp. ELISA technique was applied for serological detection of GM antigen in the patients’ serum samples. Results: The sensitivity, specificity, PPV(positive predictive value)  and NPV (negative predictive value of GM antigen ELISA testing were 100%, 74%, 36% and 100% respectively for both proven and probable cases. On applying the principle of test in series (the patient is positive if positive in both culture and the GM test), the results were improved to 100% sensitivity, 100% specificity, 100% PPV, 100% NPV and 100% accuracy. Galactomannan antigen testing proved excellent sensitivity (80%) compared to other clinical features and radiological criteria for diagnosis of probable aspergillosis and proved to be a good negative test. Conclusion: With conjunction of clinical and radiological signs, Aspergillus GM test can assist physicians in the of diagnosis of IA in patients with hematological malignancies to allow initiation of effective antifungal therapy which is ultimately important in high-risk populations.

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