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The purpose of the present study is to estimate the current incidence of febrile events (FEs) and infectious episodes in acute lymphoblastic leukemia (ALL) and evaluate the outcome. We analyzed data on all FEs in a cohort of patients affected by ALL admitted to 20 Italian hematologic centers during 21 months of observation from April 1, 2012 to December 31, 2013. Data about treatment phase, steroids, neutropenia, type and site of infection, and outcome of infection were collected. The population comprehended 271 ALL adult patients. Median age was 46 years old (range 19-75), M/F 1.1:1. We collected 179 FEs occurring during 395 different phases of treatment in 127 patients (45.3% incidence): remission induction treatment 53.1%, consolidation/maintenance 35.7%, treatment for a first or second relapse 44.3%, and refractory disease 85.7%. The incidence of FUO (fever of unknown origin) was 55/395 (13.9%). In the remaining cases, bacteria caused 92 FEs (23.2%), fungi 17 (4.3%), viruses 5 (1%). Mixed infections occurred in 10 cases mainly fungal+bacterial (9/10 cases). Neutropenia was mostly present at onset of FE (89.9% of FEs). Mortality rate was 11.7% (21/179) while 16 deaths occurred with evidence of infection (8.9%). Age > 60 years, neutropenia, poor performance status, steroids, refractory disease, and mixed infections significantly correlated with infection-related mortality. A statistically significant association with mortality was observed also for pulmonary localization and bacteremia. Our study describes the real-life epidemiological scenario of infections in ALL and identifies a subset of patients who are at higher risk for infection-related mortality. [ABSTRACT FROM AUTHOR]

The article offers information on invasive fungal diseases of the Central Nervous System (CNS) in patients suffering from hematological malignancies. Topics discussed include aspergillosis in which aspergillus infection occurs in the CNS as a site for primary or secondary localization, mucormycosis as a condition in which persistent neutropenia in hematological malignancies and diabetes prevails and neurocandidiasis which is correlated with cerebral microabscesses and subsequent encephalopathy.

It is still under debate whether granulocyte transfusions (GTs) substantially increase survival in patients with febrile neutropenia. We retrospectively examined data relative to 96 patients with hematological malignancies receiving 491 GTs during 114 infectious episodes (IE). Patients were grouped according to the median doses of granulocytes transfused during the infectious episode (low-dose group: <1.5-x108 cells/Kg; standard-dose group: 1.5–3.0x108 cells/Kg and high-dose group: >3.0x108 cells/Kg). The impact of clinical, microbiological and GT-related variables on the infection-related mortality (IRM) was investigated. The IRM was not influenced by the number of GTs or by the total amount of granulocytes received, whereas a dose-related effect of the median dose received for IE was detected at univariate analysis (IRM of 18.4% in the standard-dose group, 44.4% in the low-dose group and 48.4% in the high-dose group, p = 0.040) and confirmed at multivariate analysis (OR 3.7, IC 95% 1.5–8.9; 0.004 for patients not receiving standard doses of GTs). Moreover, patients receiving GTs at doses lower or greater than standard had increased risk for subsequent ICU admission and reduced overall survival. The dose-related effect of GTs was confirmed in bacterial but not in fungal infections. Preliminary findings obtained from a subgroup of patients candidate to GTs revealed that levels of inflammatory response mediators increase in a dose-related manner after GTs, providing a possible explanation for the detrimental effect exerted by high-dose transfusions. GTs can constitute a valuable tool to improve the outcome of infections in neutropenic patients, provided that adequate recipient-tailored doses are supplied. Further investigations of the immunomodulatory effects of GTs are recommended. [ABSTRACT FROM AUTHOR]

Background: CAR-T cell (chimeric antigen receptor T) therapy has emerged as an effective treatment of refractory hematological malignancies. Intensive care management is intrinsic to CAR-T cell therapy. We aim to describe and to assess outcomes in critically ill CAR-T cell recipients. Study design and methods: Hospital-wide retrospective study. Consecutive CAR-T cell recipients requiring ICU admission from July 2017 and December 2020 were included. Results: 71 patients (median age 60 years [37–68]) were admitted to the ICU 6 days [4–7] after CAR-T cell infusion. Underlying malignancies included diffuse large B cell lymphoma (n = 53, 75%), acute lymphoblastic leukemia (17 patients, 24%) and multiple myeloma (n = 1, 1.45%). Performance status (PS) was 1 [1–2]. Shock was the main reason for ICU admission (n = 40, 48%). Isolated cytokine release syndrome (CRS) was the most common complication (n = 33, 46%), while 21 patients (30%) had microbiologically documented bacterial infection (chiefly catheter-related infection). Immune effector cell-associated neurotoxicity syndrome was reported in 26 (37%) patients. At ICU admission, vasopressors were required in 18 patients (25%) and invasive mechanical ventilation in two. Overall, 49 (69%) and 40 patients (56%) received tocilizumab or steroids, respectively. Determinant of mortality were the reason for ICU admission (disease progression vs. sepsis or CRS (HR 4.02 [95%CI 1.10–14.65]), Performance status (HR 1.97/point [95%CI 1.14–3.41]) and SOFA score (HR 1.16/point [95%CI 1.01–1.33]). Conclusions: Meaningful survival could be achieved in up to half the CAR-T cell recipients. The severity of organ dysfunction is a major determinant of death, especially in patients with altered performance status or disease progression. [ABSTRACT FROM AUTHOR]

Background: Cancer patients may be at higher risk for severe coronavirus infectious disease-19 (COVID-19); however, the outcome of Primary Central Nervous System Lymphoma (PCNSL) patients with SARS-CoV-2 infection has not been described yet. Methods: We conducted a retrospective study within the Lymphomes Oculo-Cérébraux national network (LOC) to assess the clinical characteristics and outcome of SARS-CoV-2 infection in PCNSL patients (positive real-time polymerase chain reaction of nasopharyngeal swab or evocative lung computed tomography scan). We compared clinical characteristics between patients with severe (death and/or intensive care unit admission) and mild disease. Results: Between March and May 2020, 13 PCNSL patients were diagnosed with SARS-CoV-2 infection, 11 (85%) of whom were undergoing chemotherapy at the time of infection. The mortality rate was 23% (3/13), and two additional patients (15%) required mechanical ventilation. Two patients (15%) had no COVID-19 symptoms. History of diabetes mellitus was more common in severe patients (3/5 vs 0/8, p = 0.03). Two patients recovered from COVID-19 after mechanical ventilation during more than two weeks and resumed chemotherapy. In all, chemotherapy was resumed after COVID-19 recovery in nine patients (69%) after a median delay of 16 days (range 3–32), none of whom developed unusual chemotherapy complication nor SARS-Cov2 reactivation. Conclusion: This preliminary analysis suggests that, while being at higher risk be for severe illness, PCNSL patients with COVID-19 might be treated maximally especially if they achieved oncological response at the time of SARS-CoV-2 infection. Chemotherapy might be resumed without prolonged delay in PCNSL patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukaemia (AML) patients are at high risk of invasive aspergillosis (IA) after first induction chemotherapy (CHT). Although IA risk factors have been identified, few data are available on impact of IA, occurring during induction phase, on overall AML outcome. Patients and results: The end point of this multicentre, case‐control, study was to evaluate whether IA, occurring after first induction CHT, can affect treatment schedule and patient's outcome. We identified 40 AML patients (cases) who developed IA during first induction phase, 31 probable (77.5%) and 9 proven (22.5%). These cases were matched with a control group (80 AML) without IA, balanced according to age, type of CHT, AML characteristics and cytogenetic‐molecular risk factors. The overall response rate to induction CHT was the same in the 2 groups. In the 40 cases with IA, the overall response rate to antifungal treatment was favourable (80%) but it was significantly affected by the achievement of leukaemia complete remission (CR) with induction CHT. In fact, in cases with AML responsive to induction CHT, responses of IA to antifungal therapy were 96% compared to 21% in cases of AML not responsive to induction treatment (P <.0001). The adherence to the schedule and full doses of CHT were reported in 35% of cases (14/40) and in 76% of controls (61/80) (P =.0001; OR 6.7; 95% CI 2.7‐16.6). After first induction CHT, a significant higher number of cases (15/40; 37.5%) compared to controls (9/80; 11%) could not receive additional cycles of CHT (P =.0011, OR 4.8; 95% CI 1.9‐12.3). The IA‐related mortality was 22.5%. The median OS of cases was significantly worse than OS of controls with a difference of 12.3 months (12.1 vs 24.4 months, P =.04). However, the occurrence of IA during first induction phase did not have a significant impact on the OS of cases who achieved a CR of AML with induction CHT which are able to proceed, despite the IA, with their therapeutic program, achieving the same OS as the control group with AML in CR (P = ns). Conclusions: These data show that IA during first induction CHT can delay the subsequent therapeutic program and has a significant impact on OS, specifically in AML patients who did not achieved a CR of AML with the first course of CHT. [ABSTRACT FROM AUTHOR]

Patients with haematological malignancies are at high risk of infection because of various mechanisms of humoral and cell-mediated immune deficiencies, which mainly depend on underlying disease and specific therapies. Some of these infections are vaccine preventable. However, these malignancies are different from each other, and the treatment approaches are diverse and rapidly evolving, so it is difficult to have a common programme for vaccination in a haematology ward. Additionally, because of insufficient training about the topic, vaccination is an area often neglected by haematologists, and influenced by cultural differences, even among health-care workers, in compliance to vaccines. Several issues are encountered when addressing vaccination in haematology: the small size of the cohorts that makes it difficult to show the clinical benefits of vaccination, the subsequent need to rely on biological parameters, their clinical pertinence not being established in immunocompromised patients, scarcity of clarity on the optimal timing of vaccination in complex treatment schedules, and the scarcity of data on long-term protection in patients receiving treatments. Moreover, the risk of vaccine-induced disease with live-attenuated vaccines strongly limits their use. Here we summarise guidelines for patients without transplantations, and address the issue by the haematological group-myeloid and lymphoid-of diseases, with a special consideration for children with acute leukaemia. [ABSTRACT FROM AUTHOR]

Infection is a main concern after haemopoietic stem cell transplantation (HSCT) and a major cause of transplant-related mortality. Some of these infections are preventable by vaccination. Most HSCT recipients lose their immunity to various pathogens as soon as the first months after transplant, irrespective of the pre-transplant donor or recipient vaccinations. Vaccination with inactivated vaccines is safe after transplantation and is an effective way to reinstate protection from various pathogens (eg, influenza virus and Streptococcus pneumoniae), especially for pathogens whose risk of infection is increased by the transplant procedure. The response to vaccines in patients with transplants is usually lower than that in healthy individuals of the same age during the first months or years after transplant, but it improves over time to become close to normal 2-3 years after the procedure. However, because immunogenic vaccines have been found to induce a response in a substantial proportion of the patients as early as 3 months after transplant, we recommend to start crucial vaccinations with inactivated vaccines from 3 months after transplant, irrespectively of whether the patient has or has not developed graft-versus-host disease (GvHD) or received immunosuppressants. Patients with GvHD have higher risk of infection and are likely to benefit from vaccination. Another challenge is to provide HSCT recipients the same level of vaccine protection as healthy individuals of the same age in a given country. The use of live attenuated vaccines should be limited to specific situations because of the risk of vaccine-induced disease. [ABSTRACT FROM AUTHOR]

Posaconazole prophylaxis was compared to itraconazole prophylaxis in a real-life setting in 353 patients with acute myeloid leukemia during the first induction chemotherapy. Posaconazole prophylaxis confers an advantage in terms of both breakthrough invasive fungal diseases and overall survival compared with itraconazole.Background. To analyze the efficacy of antifungal prophylaxis (AFP) with posaconazole and itraconazole in a real-life setting of patients with acute myeloid leukemia (AML) during the first induction of remission.Methods. From January 2010 to June 2011, all patients with newly diagnosed AML were consecutively registered and prospectively monitored at 30 Italian hematological centers. Our analysis focused on adult patients who received intensive chemotherapy and a mold-active AFP for at least 5 days. To determine the efficacy of prophylaxis, invasive fungal disease (IFD) incidence, IFD-attributable mortality, and overall survival were evaluated.Results. In total, 515 patients were included in the present analysis. Posaconazole was the most frequently prescribed drug (260 patients [50%]) followed by fluconazole (148 [29%]) and itraconazole (93 [18%]). When comparing the groups taking posaconazole and itraconazole, there were no significant differences in the baseline clinical characteristics, whereas there were significant differences in the percentage of breakthrough IFDs (18.9% with posaconazole and 38.7% with itraconazole, P < .001). The same trend was observed when only proven/probable mold infections were considered (posaconazole, 2.7% vs itraconazole, 10.7%, P = .02). There were no significant differences in the IFD-associated mortality rate, while posaconazole prophylaxis had a significant impact on overall survival at day 90 (P = .002).Conclusions. During the last years, the use of posaconazole prophylaxis in high-risk patients has significantly increased. Although our study was not randomized, it demonstrates in a real-life setting that posaconazole prophylaxis confers an advantage in terms of both breakthrough IFDs and overall survival compared to itraconazole prophylaxis.Clinical Trials Registration. NCT01315925. [ABSTRACT FROM AUTHOR]

The article discusses a study which found progressive increase in the incidence of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) among bloodstream infection (BSI) caused by gram-negative bacteria in hematologic malignancy patients who were admitted in a hospital in Rome, Italy from January 2009 through December 2012. It cites the factors that contribute to the high mortality rate related to KPC-Kp BSI. It also highlights steps to prevent the spread of the KPC-Kp strains.