Invasive fungal infections in hematology: epidemiology and risk factors

Recent Italian and International epidemiological data show that invasive fungal infections (IFI), particularly aspergillosis, are still a crucial issue for patients with acute myeloid leukemia. However, in the last years the epidemiology is changing, and in order to determine the real risk of a patient and in order to improve preventive, diagnostic and therapeutic measures, it's important to identify all the factors (e.g. age, performance status, prophylaxis) that play a role in the development of IFI. Immunogenetics may potentially contribute to improve diagnosis providing new therapeutic tools, but results are limited by sample size and absence of thorough functional characterization moreover lack of replication limits translation of data to the clinical practice. Regarding candidemia an Italian study showed that the overall incidence remained unchanged between 2008 and 2010 but with an increase in the number of C. albicans aand C. glabrata infections

Clinical Aspects and Therapy of Sporadic Burkitt Lymphoma

Burkitt’s lymphoma is a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants, sharing many morphologic and immunophenotypic features. It is characterized by a high proliferation rate and propensity for extranodal sites such as gastrointestinal tract and reproductive organs. Brief-duration, high-intensity chemotherapy regimens including aggressive central nervous system prophylaxis have had remarkable success in the treatment of this disease in the sporadic form, with very high complete remission rate and overall survival in adults. Although Burkitt’s lymphoma is extremely chemosensitive, biologically targeted therapies should be developed, because current treatment options are suboptimal for patients with poor prognostic features or with relapsed disease

Assessing eligibility for treatment in acute myeloid leukemia in 2023

Introduction: Age has historically been considered the main criterion to determine eligibility for intensive chemotherapy in patients with acute myeloid leukemia (AML), but age alone can no longer be considered an absolute indicator in determining which patients should be defined as unfit. Assessment of fitness for a given treatment today serves an important role in tailoring therapeutic options. Areas covered: This review examines the main options used in real-life to define eligibility for intensive and non-intensive chemotherapy in patients with AML, with a main focus on the Italian SIE/SIES/GITMO Consensus Criteria. Other published real-life experiences are also reviewed, analyzing the correlation between these criteria and short-term mortality, and thus expected outcomes. Expert opinion: Assessment of fitness is mandatory at diagnosis to tailor treatment to the greatest degree possible, evaluating the patient's individual profile. This is especially relevant when considering the availability of newer, less toxic therapeutic regimens, which have shown promising results in patients with AML who are older or considered unfit for intensive treatment. Fitness assessment is now a fundamental part of AML management and a critical step that can potentially influence outcomes and not just predict them

Patients' preferences for chronic lymphocytic leukemia treatment: The CHOICE study

Chronic lymphocytic leukemia (CLL) therapies differ in efficacy, side effects, route, frequency, and duration of administration. We assessed patient preferences for treatment attributes and evaluated associations with disease stage, treatment line, and socio-demographic characteristics in a cross sectional, observational study conducted at 16 Italian hematology centers. Study visits occurred between February and July 2020; 401 adult patients with CLL (201 Watch and Wait (W & W), 200 treated) participated in a discrete choice experiment (DCE), composed of 8 choices between pairs of treatment profiles with different levels of 5 attributes of currently available CLL treatments (length of response, route and duration of administration, risk of side effects including diarrhea, infections, or organ damage). Health-related quality of life was assessed with the EQ-5D-5L, EORTC QLQ-C30 and QLQ CLL-16. Previously treated patients had longer disease duration (7 vs. 5 years), higher prevalence of serious comorbidities (45.5% vs. 36.2%) and high-risk molecular markers (unmutated IGHV 55.6% vs. 17.1%; TP53 mutation 15.2% vs. 4.0%). Health-related quality of life scores were similar between groups. In the DCE, W & W patients rated "possible occurrence of infections" highest (relative importance [RI] = 36.2%), followed by "treatment and relevant duration" (RI = 28.0%) and "progression-free survival (PFS)" (RI = 16.9%). Previously treated patients rated "treatment and relevant duration" highest (RI = 33.3%), followed by "possible occurrence of infections" (RI = 28.8%), "possible occurrence of organ damage" (RI = 19.4%), and "PFS" (RI = 9.8%). Concern over infection was rated highest overall; unexpectedly PFS was not among the most important criteria in either group, suggesting that the first COVID-19 pandemic wave may have influenced patient preferences and concerns about CLL therapy options

Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation

BACKGROUND: The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown. METHODS: We screened an initial cohort of 268 patients undergoing hematopoietic stem-cell transplantation (HSCT) and their donors for PTX3 SNPs modifying the risk of invasive aspergillosis. The analysis was also performed in a multicenter study involving 107 patients with invasive aspergillosis and 223 matched controls. The functional consequences of PTX3 SNPs were investigated in vitro and in lung specimens from transplant recipients. RESULTS: Receipt of a transplant from a donor with a homozygous haplotype (h2/h2) in PTX3 was associated with an increased risk of infection, in both the discovery study (cumulative incidence, 37% vs. 15%; adjusted hazard ratio, 3.08; P=0.003) and the confirmation study (adjusted odds ratio, 2.78; P=0.03), as well as with defective expression of PTX3. Functionally, PTX3 deficiency in h2/h2 neutrophils, presumably due to messenger RNA instability, led to impaired phagocytosis and clearance of the fungus. CONCLUSIONS: Genetic deficiency of PTX3 affects the antifungal capacity of neutrophils and may contribute to the risk of invasive aspergillosis in patients treated (Funded by the European Society of Clinical Microbiology and Infectious Diseases and others) .with HSCT.Supported by grants from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) (to Dr. Carvalho); the German Ministry for Education and Science (03Z2JN21, to Dr. Kurzai); the European Commission (FP7-HEALTH-2009-260338, to Dr. Romani; FP7-HEALTH-2011-280873, to Dr. Mantovani), the European Research Council (ERC-2008-AdG-233417, to Dr. Mantovani; ERC-2011-AdG-293714, to Dr. Romani), Associazione Italiana per la Ricerca sul Cancro (99629, to Dr. Mantovani); and Fundacao para a Ciencia e Tecnologia, Portugal (SFRH/BPD/46292/2008, to Dr. Carvalho; SFRH/BD/65962/2009, to Dr. Cunha; and SFRH/BPD/70783/2010, to Dr. Almeida)

Invasive fungal infections in patients with acute myeloid leukcemia and in those submitted to allogenic hemopoietic stem cell transplant: Who is at highest risk?.

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Risks for infection in patients with myelodysplasia and acute leukemia

Purpose of review Aim of the present review is to analyze the main parameters that may influence the onset of bacterial, fungal and viral infections in patients with myelodysplastic syndromes, acute myeloid leukemia and acute lymphoid leukemia. Recent findings The identification of factors influencing the onset of infections in high-risk patients is becoming one of the most important strategies to identify those patients who would really benefit from prophylactic and timely treatment. During the past few years several studies have been conducted to evaluate the impact of risk factors that may influence both the onset and the outcome of infections. The role of some of them is well defined (i.e. neutropenia, central venous catheters), whereas other factors are now emerging as new possible causative factors (i.e. iron overload, hospitalization). Summary Many factors have to be considered when evaluating the infectious risk in hematological patients. In current clinical practice the good knowledge of them may favor a better management of infectious risk, with a reduction of mortality rate

Italian Hema e-Chart Group.Continuous surveillance of invasive fungal infection: a realistic goal for the near future.

Using the Prospective Antifungal Therapy (PATH) Alliance registry, Neofytos et al. [1] investigated the epidemiology and outcome of invasive fungal infections (IFIs) in hematopoietic stem cell transplant (HSCT) recipients. Because use ofWeb-based registries is pivotal for progress in understanding IFIs, the Italian Hema e-Chart Group is also engaged in a prospective, multicenter, observational study designed to analyze all febrile events in patients with hematological malignancie