Introduction Etiological diagnosis of fever in sickle cell disease (SCD) children is often challenging. Objective: to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods Prospective, case-control study of febrile and steady-state SCD children carried out during 3 years. Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (78 cases and 59 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI) and 33 no proven infection (NPI). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences, respectively). Conclusion We found that IL-6 (optimal cut-off value of 125 pg/ml) was a very good marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, IL-6 may be useful, alone or combined with other biomarkers, to guide the management of these patients.

BACKGROUND. Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in immunosuppressed children. We aim to describe the epidemiology and clinical parameters of IFD in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity during the last 14 years. METHODS. We retrospectively reviewed the medical records of children (up to 18 years old) admitted for IFD to the PHOU of a tertiary hospital in Madrid (Spain), between 2006-2019. Epidemiological, diagnostic and therapeutic parameters were compared according to the type of infection, study period (considering 3 equivalent time fractions) and outcome. RESULTS. Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (13 males, median 10 years old). Five episodes of candidemia (all in the first period) and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. Most episodes (71.4%) occurred in high-risk children receiving antifungal prophylaxis. Eight children required intensive care and six died during treatment. Mold infections occurred in older children (126 vs. 21 months; p=0,045), increased over time (p=0.002) and were more common in high-risk compared to low-risk children (87% vs. 0%; p=0.001). There were no differences in mortality rates between periods, types of infection or underlying conditions. CONCLUSIONS. Yeast infections decreased within the study time and mold infections were more frequent in high-risk patients. A rising activity in our PHOU and an increase in the complexity of pathologies were not followed by an increase in mortality rates.

BACKGROUND The use of azoles for antifungal prophylaxis after familial allogeneic stem cell transplantation in children (SCT) is hindered by adverse events and drug interactions especially in children affected by sickle cell disease. Intermittent, higher dose of micafungin could be an alternative. METHODS A prospective, observational, longitudinal, single-center study was conducted between May 2015 and June 2018. The study included 30 patients between 2 and 18 years old who underwent allogeneic SCT and received prophylaxis with micafungin on alternating days after the bone marrow engraftment phase. FINDINGS Fifty transplants performed, 30 included prophylaxis against IFIs, with micafungin in an alternating pattern according to the previously described protocol. The indication for HSCT was hemoglobinopathies in 76.7%, acute leukemia in 20.0% and Fanconi anemia in 3.3%. The prophylaxis duration was 2.33 months (1.53 to 3.98). In our study, 40.0% (12/30) of the patients had acute GVHD, and 6.7% (2/30) had chronic GVHD, which prolonged the duration of alternating prophylaxis. No serious adverse effects of the use of micafungin were observed in any of the patients. There was also no breakthrough Invasive fungal infection (IFI) during alternating prophylaxis. CONCLUSION: In selected patients, micafungin was well tolerated without breakthrough IFI in our study.