Neutropenic enterocolitis in hemato-oncological patients

Background Neutropenic enterocolitis (NE) is a life-threatening complication in patients undergoing intensive chemotherapy for hematological malignancies. Aims of this study were to analyze the clinical presentation, diagnostic findings, management and outcome of NE and to explore factors associated with adverse outcome. Methods This study describes the presentation and outcome of NE in hemato-oncological patients hospitalized for intensive chemotherapy in the isolation unit of the Infectious Diseases Service at CHUV in 2008 and 2012. Cases were identified from the institutional database and clinical data retrospectively extracted from medical charts. Results 32 out of 199 hemato-oncological patients (16.1%) presented 35 episodes of NE. According to predefined clinical and radiological/histopathological diagnostic criteria, NE was classified as definite in 14, probable in 19, and possible in 2 cases. Induction or induction-reinduction chemotherapy for acute myeloid leukemia was the most frequent hemato-oncological setting. The triad of neutropenia, fever and digestive symptoms was present in all patients. Bowel wall thickening > 4 mm at CT scan was found in 63.6% of cases. In 34.3% of episodes a bacterial bloodstream infection was documented. Despite a Candida gastrointestinal colonization in more than two thirds of cases, invasive candidiasis was documented in only two cases (5.7%). An adverse outcome was observed in 20% of patients: 4 (11.4%) patients had severe sepsis, two (5.7%) septic shock, 6 (17.1%) were admitted to the ICU, one (3%) underwent an endoscopic intervention and recovered, and two patients died (5.7%): in one (3%) death was attributed to NE. High-dose cytarabine resulting in prolonged agranulocytosis and severe mucosal damage was associated with adverse outcome of NE. Conclusion This exploratory study reveals the determinant role of intensive chemotherapy for acute myeloid leukemia and especially of high-dose cytarabine in the occurrence of NE. The severe hematological and mucosal toxicity of this regimen are major components in the pathogenesis of NE and are associated with adverse outcome. These findings may help to identify patients at high risk for complications who need prompt management, close follow-up and maybe antimicrobial prophylaxis

Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse

This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11)(p11.2;q23) with MLL-AF10 and the second a t(11;19)(q23;p13.1) with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis). Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD), based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, all patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting

Role of Management Strategies in Reducing Mortality From Invasive Fungal Disease in Children With Cancer or Receiving Hemopoietic Stem Cell Transplant

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Beta-D-glucan in patients with haematological malignancies

(1-3)-beta-D-glucan (BDG) is an almost panfungal marker (absent in zygomycetes and most cryptococci), which can be successfully used in screening and diagnostic testing in patients with haematological malignancies if its advantages and limitations are known. The aim of this review is to report the data, particularly from the last 5 years, on the use of BDG in haematological population. Published data report mainly on the performance of the Fungitell™ assay, although several others are currently available, and they vary in method and cut-off of positivity. The sensitivity of BDG for invasive fungal disease (IFD) in haematology patients seems lower than in other populations, possibly because of the type of IFD (lower sensitivity was found in case of aspergillosis compared to candidiasis and pneumocystosis) or the use of prophylaxis. The specificity of the test can be improved by using two consecutive positive assays and avoiding testing in the case of the concomitant presence of factors associated with false positive results. BDG should be used in combination with clinical assessment and other diagnostic tests, both radiological and mycological, to provide maximum information. Good performance of BDG in cerebrospinal fluid (CSF) has been reported. BDG is a useful diagnostic method in haematology patients, particularly for pneumocystosis or initial diagnosis of invasive fungal infections

New Strategies for Treatment of Sepsis

This book represents a collection of paper from different specialists involved in the management of septic patients, aimed to disseminate the knowledge in the field of sepsis, particularly to non-intensivists physicians

Resistance in Candida albicans: exploring the cell wall barrier by proteomics

The incidence of candidiasis has dramatically increased and bloodstream infections due to different species of Candida are becoming a prime cause of morbidity and mortality in different types of immunocompromised patients. Azole and echinocandin drug resistance accounts for the dramatic increase in incidence of nosocomial bloodstream candidiasis found in recent years. Cell wall constitutes the barrier between the yeast and the host and resistant strains change the proteome of this compartment. In the last decade different proteomic platforms have been applied to study cell wall and markers of resistance to drugs have been pointed out. Modulation of these proteins seem to suggest that although resistance is based on a specific mutation able to counteract the toxicity of the antifungal drug, a set of other molecular modifications takes place contemporary or subsequently the establishment of the resistance and seems to support the viability of the resistant yeast. Profiled proteins by proteomics may be valuable in design therapy using classical antifungal along with complementary drugs able to abolish pathways that strengthen the resistance and attenuate virulence of the mutated cell

A 5-year review of invasive fungal infection at an academic medical center

Background: Invasive fungal infection (IFI) is one of the most common nosocomial infections. However, data on the epidemiology of IFI and susceptibility to antifungal agents in China are quite limited, and in particular, no current data exist on the microbiological, and clinical characteristics of IFI patients in Northeast China. Objectives: The purpose of this study was to provide a retrospective review of the clinical characteristics, laboratory test results, and risk factor predictions of inpatients diagnosed with IFI. Multivariate regression analysis was used to assess prognostic factors associated with the mortality of these patients. Methods: We retrospectively analyzed the results from 509 patients with IFI extracted from the First Hospital of China Medical University from January 2013 to January 2018. Results: Neutrophil numbers, total bilirubin, length of stay in the ICU, renal failure, use of immunosuppressants within the past 30 days, stomach tube placement and septic shock were risk factors for death from IFI. Recent surgery (within 2 weeks) and drainage tube placement did not increase mortality in these IFI patients. Increased serum levels of PCT (AUC 0.601, 95% CI 0.536–0.665, P = 0.003) and CRP (AUC 0.578, 95% CI 0.512–0.644, P = 0.020) provided effective predictors of 30-day mortality rates. Conclusions: We report for the first time epidemiological data on invasive fungal infections in Northeast China over the past 5 years. Despite the limited available clinical data, these findings will greatly aid clinical health care workers with regard to the identification, prevention, and treatment of IFI in hospitalized patients