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Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4 th European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient's risk factors for resistant bacteria and for a complicated clinical course. An 'escalation' approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A 'deescalation' approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72-96 h should be based on the patient's clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n 2 0 1 3 increasing resistance. The draft of these guidelines was discussed by the Expert Group at the ECIL-4 meeting in September 2011 and considers: i) bacterial epidemiology in neutropenic patients; ii) risk factors for resistance; iii) escalation and deescalation approaches; iv) the appropriate duration of empirical therapy; iv) non-conventional therapies against multi-resistant pathogens; and v) other issues on the management of bacterial infections in these patients. Up-dated slide sets from ECIL-4 covering these aspects are available on the websites of the four organizations involved in ECIL: the European Group for Blood and Marrow Transplantation, the European Organisation for Research and Treatment of Cancer, the Immunocompromised Host Society (ECIL), and the European Leukaemia Net. 12,13 This article summarizes the main ECIL recommendations on the initial empirical therapy of bacterial infections, but will also be valuable for the management of the many nonneutropenic but severely-immunosuppressed hematology patients. MethodsThe methodology of the ECIL conferences has been described previously. 11A working group of experts in the field of infectious diseases, microbiology or hematology was constituted, and reviewed the published literature in order to prepare proposals covering the following aspects: 1) empirical antibiotic therapy for...

Memory B cells, unlike naive B cells, require a reduced level of STAT3 activation to differentiate into antibody-secreting plasmablasts in response to IL-10 and IL-21; however, this process requires IL-21R expression in both naive and memory cells.

Information on incidence, and factors associated with mortality is a prerequisite to improve outcome after hematopoietic stem cell transplantation (HSCT). Therefore, 55′668 deaths in 114′491 patients with HSCT (83.7% allogeneic) for leukemia were investigated in a landmark analysis for causes of death at day 30 (very early), day 100 (early), at 1 year (intermediate) and at 5 years (late). Mortality from all causes decreased from cohort 1 (1980-2001) to cohort 2 (2002-2015) in all posttransplant phases after autologous HSCT. After allogeneic HSCT, mortality from infections, GVHD, and toxicity decreased up to 1 year, increased at 5 years; deaths from relapse increased in all post-transplant phases. Infections of unknown origin were the main cause of infectious deaths. Lethal bacterial and fungal infections decreased from cohort 1 to cohort 2, not unknown or mixed infections. Infectious deaths were associated with patient-, disease-, donor type, stem cell source, center, and country-related factors. Their impact varied over the post-transplant phases. Transplant centres have successfully managed to reduce death after HSCT in the early and intermediate post-transplant phases, and have identified risk factors. Late post-transplant care could be improved by focus on groups at risk and better identification of infections of "unknown origin".

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