Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.

BackgroundSaprochaete clavata (formerly Geotrichum clavatum, now proposed as Magnusiomyces clavatus) is a filamentous yeast-like fungus that has recently been described as an emerging pathogen mostly in patients with acute leukemia.MethodsThis is a retrospective study of patients diagnosed with proven and probable S. clavata infection at the University Hospital, Hradec Králové, Czechia between March 2005 and December 2017. Previous cases were identified from the literature and FungiScope® database.ResultsSix new cases (5 females, 1 male) of blood-stream S. clavata infections at the hemato-oncological department were described including epidemiological data of additional 48 patients colonized with the species. Overall, 116 strains of S. clavata were isolated from different clinical specimens of 54 patients; most of them belonged to the respiratory tract (60.3%). S. clavata was the most frequent species among arthroconidial yeasts (Trichosporon, Galactomyces, Magnusiomyces) recovered from the blood. All our patients with S. clavata infection had profound neutropenia, a central venous catheter, broad-spectrum antibiotics and antifungal prophylaxis; four had a history of a biliary tract system disease. The diagnosis was based on a positive blood culture in all patients. Four patients died of multiorgan failure and sepsis despite treatment with lipid-based amphotericin B and/or voriconazole. From the literature and FungiScope database, 67 previous cases of S. clavata infections were evaluated in context of our cases.ConclusionSaprochaete clavata infection represents a life-threatening mycosis in severely immunocompromised patients. The successful outcome of treatment seems to be critically dependent on the early diagnosis and the recovery of underlying conditions associated with immune dysfunction or deficiency.

The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1-27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3% of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high-pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml(-1) (range <0.20-13.47 μg ml(-1)). Significant inter- and intra-patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice.

Objective: With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. Design: We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. Methods: Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (LT 4 ) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. Results: During LT 4 treatment, significant increases (all P!0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 mg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P!0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. Conclusions: An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.