Safety & efficacy of antibiotic de-escalation and discontinuation in high-risk haematological patients with febrile neutropenia: a single-centre experience

Background There is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the 4th European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk haematological patients. Methods We studied 446 admissions after introduction of an ECIL-4 based protocol (= ECIL-4 group) in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteraemia and antibiotic consumption. Results Bacteraemia occurred more frequently in the ECIL-4 group [46.9% (209/446) vs 30.5% (156/512); p<0.001], without an associated increase in septic shock [4.7% (21/446) vs 4.5% (23/512); p=0.878] or infection-related ICU admission [4.9% (22/446) vs 4.1% (21/512); p=0.424]. Overall mortality was significantly lower in the ECIL-4 group [0.7% (3/446) vs 2.7% (14/512); p=0.016], resulting mainly from a decrease in infection-related mortality [0.4% (2/446) vs 1.8% (9/512); p=0.058]. Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 versus 14; p=0.001) and 7 daily antibiotic doses (17 versus 24; p<0.001) per admission period. Conclusions Our results support implementation of ECIL-4 recommendations to be both safe and effective based on real world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.

Highly sensitive HBsAg, anti-HBc and anti HBsAg titres in Early Diagnosis of HBV Reactivation in Anti-HBc-Positive onco-haematological Patients.

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for > 18 months were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27–40509) IU/ml, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median [IQR]: 81[49–541] U/L). An anti-HBc>3 cut-off index (COI) plus anti-HBs persistently/declining to <50 mIU/ml was predictive for HBV-R (OR [95% CI]: 9.1 [2.7–30.2]; 63% of patients with vs. 15% without this combination experienced HBV-R, P<0.001). The detection of highly sensitive (HS) HBsAg and/or HBV-DNA confirmed at > 2 time points, also predicts HBV-R (OR [95% CI ]: 13.8 [3.6–52.6]; 50% of positive vs. 7% of negative patients to these markers experienced HBV-R, P=0.001).HS-HBs and anti-HBc titration proved useful early markers of HBV-R.The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring.

Cytomegalovirus in Haematological Tumours

The exquisite coupling between herpesvirus and human beings is the result of millions of years of relationship, coexistence, adaptation, and divergence. It is probably based on the ability to generate a latency that keeps viral activity at a very low level, thereby apparently minimising harm to its host. However, this evolutionary success disappears in immunosuppressed patients, especially in haematological patients. The relevance of infection and reactivation in haematological patients has been a matter of interest, although one fundamentally focused on reactivation in the post-allogeneic stem cell transplant (SCT) patient cohort. Newer transplant modalities have been progressively introduced in clinical settings, with successively more drugs being used to manipulate graft composition and functionality. In addition, new antiviral drugs are available to treat CMV infection. We review the immunological architecture that is key to a favourable outcome in this subset of patients. Less is known about the effects of herpesvirus in terms of mortality or disease progression in patients with other malignant haematological diseases who are treated with immuno-chemotherapy or new molecules, or in patients who receive autologous SCT. The absence of serious consequences in these groups has probably limited the motivation to deepen our knowledge of this aspect. However, the introduction of new therapeutic agents for haematological malignancies has led to a better understanding of how natural killer (NK) cells, CD4+ and CD8+ T lymphocytes, and B lymphocytes interact, and of the role of CMV infection in the context of recently introduced drugs such as Bruton tyrosine kinase (BTK) inhibitors, phosphoinosytol-3-kinase inhibitors, anti-BCL2 drugs, and even CAR-T cells. We analyse the immunological basis and recommendations regarding these scenarios.

Italian onco-haematological patients’ preferences in bad news communication: a preliminary investigation

Background The manner in which bad news is communicated in oncological contexts can affect patients’ engagement, their coping strategies and therapeutic compliance. Although this topic has been broadly investigated since the nineties, to the best of our knowledge, little has been written about Italian patients’ experiences and preferences concerning what the oncologists should disclose and how they should intimate patients about their health conditions in different stages of oncological disease. Methods In an attempt to fill this gap, an online self-report questionnaire was administered to a sample of Italian onco-haematological patients. Data were analysed both qualitatively (by a content analysis) and quantitatively (by descriptive analysis and Generalized Linear Mixed Model). Results While the majority of patients elected to know the truth during their clinical course, a polarisation between those arguing that the truth be fully disclosed and those claiming that the truth be communicated in a personalised way was observed at the attitude level. Among demographic variables accounted for, age seems to most affect patients’ preferences. Indeed, younger Italian patients decidedly reject concealment of the truth, even when justified by the beneficence principle. This result could be a reaction to some protective and paternalistic behaviours, but it could even reflect a relation according to which the more the age increases the more the fear of knowing rises, or an intergenerational change due to different ways of accessing the information. The qualitative analysis of the final open-ended question revealed three main sources of problems in doctor-patient encounters: scarcity of time, absence of empathy and use of not-understandable language that makes it difficult for patients to assume a more active role. Conclusions The results of the present study, which represents a preliminary step in the subject investigation, will be deployed for the construction and validation of a more sophisticated questionnaire. Better awareness of the Italian onco-haematological patients’ preferences concerning bad news communication and truth-telling could be useful in adopting more suitable medical practices and improving doctor-patient relationships.

Validation of the EQUAL Aspergillosis Score by analysing guideline-adherent management of invasive pulmonary aspergillosis

Objectives To investigate the diagnosis and treatment standards at the University Hospital of Cologne, Germany, by applying the EQUAL Aspergillosis Score to invasive pulmonary aspergillosis (IPA) patients. Methods The charts of 103 patients with probable or proven IPA at the University Hospital of Cologne were reviewed and the score retrospectively applied to all patients. Results Patients were stratified into two groups according to the underlying disease: a haematology group (n = 76, 73.8%) and a non-haematology group (n = 27, 26.2%). While the haematology group attained 67.8% of achievable score points (median: 15; IQR: 13–18; range: 8–25), the non-haematology group reached 48.4% (median: 12 points; IQR: 9–14; range: 4–18) (P &lt; 0.001). Regarding diagnostics, haematological patients achieved 81.3% of achievable points (median: 7; IQR: 8–10; range: 3–13) and non-haematological 56.3% (median: 7; IQR: 5–9; range: 3–11). Concerning treatment, haematological patients gained 86.3% (median: 5; IQR: 5–5; range: 0–5) and non-haematological 68.1% (median: 5; IQR: 0–5; range: 0–5) of achievable points. Among the haematological patients with versus those without mould-active prophylaxis, 90 day mortality was 46.0% and 59.3% (P = 0.004), respectively. Guideline adherent management of IPA was observed in 31.1% of cases (39.5% in haematological patients and 7.4% in non-haematological). Conclusions The EQUAL Aspergillosis Score is more suitable for evaluation of management of haematological patients compared with those without such underlying disease. In both groups there was no correlation between score points and survival. Larger prospective studies may be suitable to correlate outcome and score. A revision of the score should be considered based on the data presented.

Knowledge gaps in candidaemia/invasive candidiasis in haematological cancer patients

As neutropenic patients with haematological cancer are not typically included in randomized controlled trials (RCTs) of candidaemia, there is low quality of evidence regarding the management of this common opportunistic mycosis in this patient population, which is at high risk for poor outcomes. Herein we identify the gaps in knowledge that are not addressed by the modern RCTs and candidaemia guidelines, and outline some considerations for the future clinical research agenda in candidaemia/invasive candidiasis in haematological patients.