Conflicting results have been reported regarding the association between early cytomegalovirus (CMV) reactivation and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This prompted us to evaluate the impact of CMV reactivation on outcomes of 155 consecutive adult patients transplanted in our institution. In our study, CMV reactivation did not affect cumulative incidence (CI) of relapse in patients with lymphoproliferative disorders. However, the CI of relapse in patients with myeloproliferative disorders (AML and MPN) was 37% (95% CI, 21-53) in patients without CMV reactivation as opposed to 17% (95% CI, 9-28) in patients with CMV reactivation (p = 0.03). An important correlation between CMV reactivation and relapse was found in patients with MPN; the CI of relapse was 50% (95% CI, 12-80) in patients without CMV reactivation as opposed to only 7% (95% CI, 0-27) in patients with CMV reactivation (p = 0.02). A substantial reduction of relapse in myeloproliferative disorders associated with CMV reactivation was confirmed by multivariate analysis (HR 2.73; 95% CI, 1.09-6.82, p = 0.03) using time-dependent covariates for high-risk disease, older age, RIC conditioning, ATG, grade II-IV acute, and chronic GVHD. To our knowledge, we are the first to show an association of CMV reactivation with relapse reduction in MPN patients. This putative virus vs myeloproliferation effect warrants further research.

Invasive candidosis is the most common invasive fungal infection in hospitalized patients and is associated with a high mortality rate. This is the first study from a Croatian tertiary care hospital describing epidemiology, risk factors and species distribution in patients with candidemia. A three-year retrospective observational study, from 2018 to 2020, was performed at the University Hospital Centre Zagreb, Zagreb, Croatia. A total of 160 patients with candidemia (n = 170 isolates) were enrolled. Candidemia incidence increased from 0.47 to 0.69 per 1000 admissions in 2018 and 2020, respectively. Ninety-five patients (58.38%) were in the intensive care unit. The main risk factors for candidemia were central venous catheter (CVC) (84.38%), previous surgical procedure (56.88%) and invasive mechanical ventilation (42.50%). Candida albicans was identified in 43.53% of isolates, followed by C. parapsilosis (31.76%) and C. glabrata (12.36%), C. krusei (5.29%), C. tropicalis (2.35%) and C. lusitaniae (2.35%). The study discovered a shift to non-albicansCandida species, particularly C. parapsilosis, and made it possible to determine the main tasks we should focus on to prevent candidemia in the hospital, these being mainly infection control measures directed towards prevention of catheter-related bloodstream infections, specifically comprising hand hygiene and CVC bundles of care. The potential benefit of fluconazole prophylaxis in certain populations of surgical patients could also be considered.

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Background: About 30% of Hodgkin Lymphoma (HL) patients are refractory to induction therapy or relapse. Standard salvage treatment is often followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) if at least a partial remission is achieved. However 30-50% of relapsed-refractory (R/R) patients fail to achieve PR. Recently the PD-1 targeting antibody Nivolumab has shown promising activity in HL patients relapsed after ASCT but the expected CR rate is only about 20%. Administration of nivolumab as early post-ASCT consolidation might improve results However, several reports have highlighted the relevance of patient immune-competence. In this view, T-cell count is severely depleted after ASCT. Aims: Here we report the preliminary results of a prospective trial investigating the feasibility, and the efficacy of post-ASCT Nivolumab with the support of unselected autologous lymphocyte reinfusions (ALI). Methods: HL patients under the age of 60 with active, relapsed/refractory disease who have already failed at least two chemotherapy lines and Brentuximab were eligible for the trial. All enrolled patient underwent lymphocyte aphaeresis, with a minimum target of 5x10 7 CD3+/kg. All patients then received ASCT with FEAM conditioning. After ASCT, the first ALI wasdelivered 7 days after engraftment. ALI dosing was incremental, one logarithm at each step, starting from 1x10 4 /kg in the first infusion to a maximum of 1x10 7 /kg in the fourth and last infusion. Each ALI was followed after 48 hours by the administration of Nivolumab 240 mg flat dose. The second ALI dose was administered at 14 days after the first one. The third and the fourth were given every 21 days. Lymphocyte subpopulations were extensively studied on peripheral blood samples before and after each ALI and each Nivolumab administration, by 12-colours flow cytometry. Clinical response was evaluated 21 days after completion of the fourth ALI + Nivolumab.

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Background: Detection of biomarkers, such as galactomannan (GM), has proven to be of great significance in early recognition of invasive aspergillosis (IA). The aim of our study was to evaluate the lateral flow assay (LFA) for the detection of GM on serum and bronchoalveolar lavage (BAL) samples previously proven positive by enzyme-linked immunosorbent assay (ELISA). Methods: The study was performed on serum and BAL samples obtained from patients with suspected IA in the period from February 2019 to January 2020, which were previously GM positive by ELISA (Platelia Aspergillus Ag, Biorad, Hercules, USA). Samples were then tested by LFA (Aspergillus Galactomannan LFA, IMMY, Oklahoma, USA) with test line intensity visually read as 1+, 2+, 3+, or 4+. Results: A total of 45 GM ELISA positive serum and/or BAL samples were obtained from 41 patients; 25 (55,6 %) were BAL and 20 (44,4 %) serum samples. LFA showed a positive result in 39 out of 45 (86,7%) GM ELISA positive samples; 22/25 (88.0 %) BAL samples and 17/20 (85.0 %) serum samples tested positive. In BAL samples, low intensity test line of 1+ was significantly more frequent in GM ELISA positive samples with optical density index (ODI) < 1.0 (p=0.0002). Three serum samples with high GM ELISA ODI (>4.0) had low intensity line of 1+ when tested with LFA. Conclusions: Results obtained by LFA are comparable to GM ELISA. Since low intensity lines were found in serum samples with high ODI, this potentially makes BAL a superior sample for LFA, at least when visual and not automated reading is done.

Invasive fungal infections (IFI) are an important problem of modern medicine. The reason is growing population of immunocompromised patients and high morbidity and mortality of these infections. Timely diagnosed IFI is of utmost importance because the delay of antifungal treatment has impact on treatment outcome. Cultivation as a conventional diagnostic method has low sensitivity, long duration and demands obtaining invasive samples. Therefore, in the last two decades fungal biomarkers are investigated for earlier and more sensitive diagnostics. 1,3-β-D-glucan (BDG) is a fungal biomarker in patients’ sera that enables detection of the following fungal pathogens: Candida spp., Aspergillus spp., Acremonium, Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporotrix schenckii, Saccharomyces cerevisiae and Pneumocystis jirovecii. Low level and absence of BDG in the cell wall unables the detection of Cryptococcus spp. and order Mucorales with this test. High negative predictive value of BDG can be used when deciding to stop antifungal treatment and be a part of strategy for antifungal stewardship in intensive care units. In hematological patients BDG can be used as a screening method or as a part of diagnostic work-up when IFI is suspected. Reliability of test result is higher when two or more consecutive samples are positive. Influence of antifungal prophylaxis on BDG test results is still unclear. BDG kinetics and its relation to clinical outcome are still investigated. For pediatric population cut-off values for interpretation are still not defined, although many studies have been published investigating this issue. Although still not recommended by pediatric guidelines, this test can help in certain situations having in mind its limitations. BDG as a fungal marker represents the significant progress in IFI diagnostics. With simultaneous application of other diagnostic methods, exact interpretation and rational use, it can help earlier and more successful diagnostics and treatment of IFI.