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.

Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, Gram-negative (49.4%) outweighed Gram-positive bacteria (40.9%), Escherichiacoli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P < 0.001) and neutropenia >7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. A shift towards Gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

The occurrence of unexplained peripheral blood cytopenia, particularly neutropenia, has been recently reported after rituximab. Its prevalence may be underestimated since it may occur late after treatment. This study analysed all cases of unexplained delayed-onset peripheral blood cytopenia of WHO grade II – IV occurring in an unselected series of patients treated with rituximab in order to evaluate its prevalence and clinical significance. Seventy-seven courses of rituximab (corresponding to 317 rituximab infusions) given to 72 consecutive patients affected by non-Hodgkin's Lymphoma and treated at a single Center with rituximab, alone (nine cases), associated with chemotherapy (50) or with chemotherapy and autologous stem cell transplantation (18) were evaluated. Twenty-three cases of cytopenia (29.8%) were observed. Neutropenia developed in 21 cases (27.3%), thrombocytopenia in eight (10.4%), anemia in four (5.2%). Multiple cytopenias were observed in nine cases. Neutropenia developed after a median of 10 weeks, anemia of 5 weeks and thrombocytopenia of 4 weeks after the last rituximab dose. Severe infections occurred in four of 21 neutropenic patients (19%), compared to two of 56 controls (3.6%) (p = 0.043). Cytopenia eventually resolved in nine of 18 evaluable cases after a median of 10 weeks (range 1 – 23). Age, sex, histology, bone marrow infiltration, hypogammaglobulinemia, previous chemotherapy, autologous stem cell transplant, rituximab schedule and timing, rituximab doses were analysed as predictors for cytopenia; by multivariate analysis only a previous treatment with chemotherapy and more than four rituximab doses were significantly associated with a higher risk of post-rituximab delayed cytopenia. Delayed-onset cytopenia, particularly neutropenia, is a clinically significant complication of rituximab treatment, which merits further investigation.

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.