Early Diagnosis of Invasive Aspergillosis in Neutropenic Patients. Comparison between Serum Galactomannan and Polymerase Chain Reaction

Background Invasive aspergillosis (IA) is a major cause of morbidity and mortality in profoundly neutropenic patients, so early diagnosis is mandatory. Aim Consecutive patients with hematological malignancies undergoing intensive chemotherapy were screened for IA with two different methods which were compared. Methods From October 2000 to August 2003 we tested 1311 serum samples from 172 consecutive patients with a polymerase chain reaction assay and between April 2005 and April 2008 we tested 806 serum samples from 169 consecutive patients with a Galactomannan (GM) test. Bronchoalveolar (BAL) samples were obtained whenever the patient's condition allowed and tested with either method. Results: The serum PCR assay had a sensitivity of 75.0% and a specificity of 91.9% and the serum GM assay had a sensitivity of 87.5% and a specificity of 93.1%, ( P > 0.05). The presence of two or more consecutive positive serum samples was predictive of IA for both assays. BAL GM/PCR was positive in some patients without serum positivity and in patients with 2 or more positive serum GM/PCR. Conclusions: No significant differences between the 2 serum tests were found. The GM assay has the advantage of being standardized among several laboratories and is incorporated in the criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG), however is much more expensive. BAL GM and PCR sampling aids in IA diagnosis but needs further validation studies to differentiate between colonization and true infection in cases where serum GM or PCR are negative

Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission

Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. Results: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. Conclusions: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Screening a Targeted Panel of Genes by Next-Generation Sequencing Improves Risk Stratification in Real World Patients with Acute Myeloid Leukemia

Although mutation profiling of defined genes is recommended for classification of acute myeloid leukemia (AML) patients, screening of targeted gene panels using next-generation sequencing (NGS) is not always routinely used as standard of care. The objective of this study was to prospectively assess whether extended molecular monitoring using NGS adds clinical value for risk assessment in real-world AML patients. We analyzed a cohort of 268 newly diagnosed AML patients. We compared the prognostic stratification of our study population according to the European LeukemiaNet recommendations, before and after the incorporation of the extended mutational profile information obtained by NGS. Without access to NGS data, 63 patients (23%) failed to be stratified into risk groups. After NGS data, only 27 patients (10%) failed risk stratification. Another 33 patients were re-classified as adverse-risk patients once the NGS data was incorporated. In total, access to NGS data refined risk assessment for 62 patients (23%). We further compared clinical outcomes with prognostic stratification, and observed unexpected outcomes associated with FLT3 mutations. In conclusion, this study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and underscores the need for further studies to refine the current risk classification criteria

Intercontinental study of Infectious Diseases Working Party of EBMT

prospective study on bacterial infectious complications mortality after stem cell transplantatio

Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality.

OBJECTIVES We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. METHODS Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). RESULTS The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. CONCLUSIONS Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality

B Lymphoblastic Lymphoma Presenting as a Tumor of the Nasopharynx in an Adult Patient

In adults, non-Hodgkin’s lymphoma (NHL) is the second most common neoplasm found in the head and neck region after squamous cell carcinoma. Within this region, primary NHL of the nasopharynx is rare. We report the case of a 28-year-old male diagnosed with a B lymphoblastic lymphoma (CD20−; CD79a+; CD3−; CD10+; PAX5+, CyclinD1−; TdT+) of the nasopharynx extending to the deep and superficial structures of the right hemiface, to the skull base with an intracranial component and a small but detectable bone marrow involvement, who was started on chemotherapy with a complete response. To the best of our knowledge, this is the first case of a primary nasopharynx B-LBL in an adult patient with such aggressive regional spread to be reported in the literature

Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia

International audienceMycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population—although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacterial infections is particularly complicated for patients in haematology because of the many drug–drug interactions between antimycobacterial drugs and haematological and immunosuppressive treatments. The management of mycobacterial infections must also consider the effect of delaying haematological management. We surveyed the management practices for latent tuberculosis infection (LTBI) in haematology centres in Europe. We then conducted a meticulous review of the literature on the epidemiology, diagnosis, and management of LTBI, tuberculosis, and nontuberculous mycobacterial infections among patients in haematology, and we formulated clinical guidelines according to standardised European Conference on Infections in Leukaemia (ECIL) methods. In this Review, we summarise the available literature and the recommendations of ECIL 8 for managing mycobacterial infections in patients with haematological malignancies