scholarly journals Invasive aspergillosis in acute leukemias: old and new risk factors and epidemiological trends

2011 ◽  
Vol 49 (S1) ◽  
pp. S13-S16 ◽  
Author(s):  
Morena Caira ◽  
Mario Mancinelli ◽  
Giuseppe Leone ◽  
Livio Pagano
Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Binav Baral ◽  
Prasanth Lingamaneni ◽  
Trilok Shrivastava ◽  
Maryam Zia ◽  
Ishaan Vohra ◽  
...  

Background: Invasive aspergillosis (IA) is one of the most dreaded complications in neutropenic patients with hematologic malignancies; risk significantly increases with chemotherapy, particularly during induction. It dramatically worsens the overall prognosis of the underlying malignancy and predisposes patients to undergo secondary interventions, thereby prolonging the duration of treatment and hospital stay. While prophylactic antifungal therapy has remarkably lowered the rates of IA, it remains a persistent problem in cancer treatment. The primary objective of our study is to explore the risk factors of IA in neutropenic patients with acute leukemias and its role in hospital stay, in-hospital mortality, and hospitalization costs. Methods: The Nationwide Inpatient Sample (NIS) database was queried to include all adults with acute leukemia admitted from 2012 and 2017, whose course was complicated by neutropenia. Those with and without invasive aspergillosis were compared. T-test was used to compare means of continuous variables and chi-square test to compare proportions of categorical variables. Multivariable logistic regression was used to evaluate risk factors for aspergillosis, as well as, inpatient mortality. Statistical tests for trends of resource utilization across six years were performed. Results: A total of 141,835 admissions met the inclusion criteria, of which, 2.5% had aspergillosis. Mean age (55.4 years) and gender (male 55.5%) did not significantly differ in neutropenic patients with and without aspergillosis. AML accounted for a larger proportion of the aspergillosis group (84.3% vs 76.9%, p<0.0001). Rates of HSCT and inpatient chemotherapy were comparable in both groups. Those with aspergillosis had higher inpatient mortality (15.8% vs 7.1%, p<0.0001) and more frequently required ICU-level care (12.9% vs 5.4%, p<0.0001) Independent risk factors for the development of aspergillosis included: Black race, receiving treatment at a teaching hospital, AML (compared to ALL) and poor nutritional status. On multivariate analysis, aspergillosis conferred an increased risk of inpatient mortality (aOR 2.57, 95% CI: 2.08-3.19, p<0.001), longer length of hospital stay by 7.4 days (95% CI: 6.0 to 8.8 days, p<0.001) and higher hospitalization costs by $37k per admission (95% CI: $29k-44k, p<0.001). Rates of aspergillosis decreased from 2.9% in 2012 to 2.2% in 2017 (trend P=0.03). In neutropenic acute leukemia patients without aspergillosis, there has been an improvement in inpatient mortality (from 7.3% in 2012 to 6.0% in 2017, trend P <0.01), as well as, length of hospital stay (17.5 days in 2012 to 16.7 days in 2017, trend P=0.02). However, there was no significant change in mortality or resource utilization among those with aspergillosis. Conclusions: Aspergillosis represents a significant challenge in the management of hematological malignancies. There is a delicate interplay between neutropenia and IA, with neutropenic patients more susceptible to invasive fungal infections, and IA further contributing to neutropenia. The encouraging trend in decreasing prevalence along the years is reflective of more aggressive prophylactic antifungal usage in acute leukemias, with the revised IDSA guidelines for aspergillosis being a cornerstone. However, mortality and resource utilization remain unchanged despite advances in diagnosis and treatment of aspergillosis. This data highlights the importance of prophylactic antifungals and maintaining a high index of suspicion for IA in neutropenic acute leukemia and the need of early focused treatment to improve clinical outcomes. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1551.1-1552
Author(s):  
V. Mazurov ◽  
O. Shadrivova ◽  
M. Shostak ◽  
L. Martynova ◽  
M. Tonkoshkur ◽  
...  

Background:Invasive aspergillosis (IA) is a severe opportunistic infection that is not well understood in rheumatological patients.Objectives:To study risk factors, etiology, clinical manifestations and results of treatment of IA in adult rheumatological patients.Methods:Retrospective analysis of 830 patients (1998-2019) with “proven” and “probable” IA (EORTC / MSG, 2019), adults - 699 (84%). The main group included 18 (3%) adult rheumatological patients with IA, a control group included 610 (87%) adult hematological patients. Rheumatological patients were older, the average age was 59 years (21–75) vs 45 years (18–79), p = 0.005, and among them there were more women – 56% vs 42%, p = 0.01.Results:In rheumatological patients with IA, underlying diseases were ANCA-associated vasculitis (28%), granulomatosis with polyangiitis (22%), periarteritis (11%), systemic lupus erythematosus (22%), rheumatic heart disease (11%) and ankylosing spondylitis (6%). In the control group, underlying diseases were acute leukemia (45%), lymphomas (34%), chronic leukemia (9%), multiple myeloma (7%), myelodysplastic syndrome (3%), and other hematological diseases (2%).The main risk factors for IA development in rheumatological patients were: systemic steroids use (89% vs 69%), prolonged lymphocytopenia (76% vs 65%, median - 14 vs 12 days), treatment in ICU (44% vs 18%, p = 0.01), acute or chronic renal failure (39% vs 1%, p = 0.0008) and immunosuppressive therapy (28% vs 25%). Severe neutropenia was noted significantly less frequently (18% vs 83%, p = 0.0001). Additional risk factors were decompensated diabetes mellitus (17% vs 2%, p = 0.004), previous surgery (17% vs 1%, p = 0.001) and organ transplantation (6% vs 0%). In rheumatological patients, lung (83% vs 98%, p = 0.0001) and ≥2 organs (6% vs 8%) involvement were less common. Heart (11% vs 0%), sinuses (6% vs 5%) and central nervous system (6% vs 4%) involvement more often developed. In rheumatological patients, respiratory failure (61 vs 37%, p = 0.03), hemoptysis (28% vs 7%, p = 0.0001) and chest pain (17% vs 7%, p = 0, 04) were noted more often, less often - fever ≥380С (67% vs 85%, p = 0.01) and cough (61% vs 70%). CT signs of lung damage were similar in both groups, but rheumatologic patients were more likely to show an «air crescent» sign and / or destruction cavity (44% vs 10%, p = 0.0001). In rheumatologic patients, IA was more often confirmed by isolation ofAspergillusspp. from BAL (80% vs 45%, p = 0.005) and by histological examination (22% vs 7%, p = 0.01). The main pathogens wereA. fumigatus(50% vs 43%),A. niger(29% vs 32%), andA. flavus(14% vs 17%).Rheumatological patients were less likely to receive antifungal therapy 89% vs 99%, p = 0,0003. The main drug in both groups was voriconazole. The overall 12-week survival did not significantly differ between groups, but was lower in rheumatological patients with IA (69% vs 81%).Conclusion:In rheumatological patients, invasive aspergillosis more often developed at an older age, mainly in women. The main background diseases were ANCA-associated vasculitis, granulomatosis with polyangiitis, and systemic lupus erythematosus. Typical risk factors were steroids and immunosuppressants use, prolonged lymphocytopenia, ICU stay, and renal failure. The main causative agents wereA. fumigatus,A. niger, andA. flavus. The main localization of infection were lungs. Respiratory failure, hemoptysis and heart involvement were typical. The overall 12-week survival of rheumatological patients with invasive aspergillosis was 69%.Disclosure of Interests:None declared


Leukemia ◽  
2005 ◽  
Vol 19 (4) ◽  
pp. 545-550 ◽  
Author(s):  
K Mühlemann ◽  
C Wenger ◽  
R Zenhäusern ◽  
M G Täuber

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4358-4366 ◽  
Author(s):  
Kieren A. Marr ◽  
Rachel A. Carter ◽  
Michael Boeckh ◽  
Paul Martin ◽  
Lawrence Corey

The incidence of postengraftment invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients increased during the 1990s. We determined risks for IA and outcomes among 1682 patients who received HSCTs between January 1993 and December 1998. Risk factors included host variables (age, underlying disease), transplant variables (stem cell source), and late complications (acute and chronic graft-versus-host disease [GVHD], receipt of corticosteroids, secondary neutropenia, cytomegalovirus [CMV] disease, and respiratory virus infection). We identified risk factors associated with IA early after transplantation (≤ 40 days) and after engraftment (41-180 days). Older patient age was associated with an increased risk during both periods. Chronic myelogenous leukemia (CML) in chronic phase was associated with low risk for early IA compared with other hematologic malignancies, aplastic anemia, and myelodysplastic syndrome. Multiple myeloma was associated with an increased risk for postengraftment IA. Use of human leukocyte antigen (HLA)–matched related (MR) peripheral blood stem cells conferred protection against early IA compared with use of MR bone marrow, but use of cord blood increased the risk of IA early after transplantation. Factors that increased risks for IA after engraftment included receipt of T cell–depleted or CD34-selected stem cell products, receipt of corticosteroids, neutropenia, lymphopenia, GVHD, CMV disease, and respiratory virus infections. Very late IA (> 6 months after transplantation) was associated with chronic GVHD and CMV disease. These results emphasize the postengraftment timing of IA; risk factor analyses verify previously recognized risk factors (GVHD, receipt of corticosteroids, and neutropenia) and uncover the roles of lymphopenia and viral infections in increasing the incidence of postengraftment IA in the 1990s.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Ye Li ◽  
Sunaula Shakya ◽  
Heng Long ◽  
Lian-Fa Shen ◽  
Yi-Qun Kuang

Leprosy remains endemic in some regions and is a global health concern. However, the possible causes and risk factors of the disease remain unclear. Data in Wenshan, China were collected from the Wenshan Institute of Dermatology (1986–2015); data in Nepal were obtained from the Leprosy Control Division, Department of Health Services, Nepal (2011 to 2015); and data from Indonesia, India, and Brazil were collected from WHO records. We assessed the epidemiological trends of leprosy in Wenshan and compared the features of possible causes and risk factors with those of other countries. We then performed a descriptive and statistical analysis to make our study more purposeful and definitive. A total of 3,376 cases were detected in Wenshan from 1986 to 2015. The overall prevalence rate (PR) of leprosy presented a decreasing trend with a peak (4.9/10,000 population) in 1986. The detection of new leprosy cases was higher in males than in females. Visible deformity increased every year since 2005 with a disability of 34.8% in 2015 among new cases. In Nepal, 2,461 leprosy patients received multi-drug therapy (MDT) in 2015 which corresponded to the PR of 0.89/10,000 population. Geographic latitude and socio-economic situations appeared to be the main causes of leprosy, and the healthcare condition was an important factor associated with leprosy incidence. The introduction of MDT effectively reduced leprosy prevalence worldwide. Wenshan (China), Nepal, and other countries share similarities in various aspects with respect to socio-cultural features, geographical distribution, environmental factors, and economic situation, which may contribute to leprosy being endemic in these areas.


Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1955-1959 ◽  
Author(s):  
David Ghez ◽  
Anne Calleja ◽  
Caroline Protin ◽  
Marine Baron ◽  
Marie-Pierre Ledoux ◽  
...  

Key Points Ibrutinib may be associated with invasive fungal infections especially IA. Most infections usually occur during the first months of treatment, often in patients with other risk factors for fungal infections.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18715-e18715
Author(s):  
Kristina Zakurdaeva ◽  
Olga A. Gavrilina ◽  
Anastasia N. Vasileva ◽  
Sergei Dubov ◽  
Vitaly S. Dubov ◽  
...  

e18715 Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]


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