Significant reduction in the incidence of non-coronavirus infections in patients with chronic lymphocytic leukemia on ibrutinib and venetoclax treatment during the COVID-19 pandemic: An additional benefit of lockdown.

Effective treatment and prevention of infections challenge management of patients with chronic lymphicytic leukemia (CLL). The COVID-19 pandemic resulted in the reduction of outpatient hospital visits as a part of non-pharmaceutical interventions that could affect the incidence of infectious complications. Study enrolled patients with CLL receiving ibrutinib or/and venetoclax who were observed at the Moscow City Centre of Hematology from 01 April 2017 to 31 March 2021. We found a reduction in the incidence of infectious episodes after the implementation of the lockdown in Moscow in 01 April 2020, when compared to data on the year prior to the lockdown (p < 0.0001), as well as when compared to the predictive model (p = 0.02), and based on individual infection profiles using cumulative sums (p < 0.0001). Bacterial infections had 4.44-fold decrease, bacterial in combination with undefined infections had 4.89-fold decrease, viral infections had unsignificant changes. The decrease in the number of outpatient visits coincides with the time of the lockdown could be a likely factor, explaining a decline in the incidence of infection. Patients were clustered according incidence and severity of infectious episodes for subgroup mortality assessment. No differences in overall survival due to COVID-19 were observed. Typical respiratory infections, bacterial and undefined, the transmission of which may be affected by patient-to-patient contact in the settings of out-patient health care visits were decreased, possibly due to SARS-CoV-2 restrictive measures. A positive correlation between outpatient visits and the incidence of bronchial and upper respiratory tract infection points at the role of hospital-acquired infection and attests to the necessity of reorganizing care for all patients with CLL.

COVID-19 in patients with chronic lymphocytic leukemia: a Moscow observational study.

We describe a retrospective cohort, 156 patients with chronic lymphocytic leukemia (CLL) diagnosed with COVID-19, analyze factors associated with a severe disease course and the effects of various treatment regimens. Anti-SARS-CoV-2 IgG and IgM levels are significantly lower. Patients with CLL are more likely to have a severe course of COVID-19, with IL-6 levels acting as a consistent biomarker of disease severity. Ten patients had recurrent episodes, fatality rate of 20%. Overall survival did not differ between patients receiving ibrutinib monotherapy and anti-CD20 antibodies ± chemotherapy. It seems that the immunodeficiency inherent to CLL influences outcomes to a larger degree than does the treatment. Glucocorticoids are not associated with significant OS improvement whereas anti-cytokine compounds usage seemed to be beneficial in patients with mild pulmonary involvement. Our data attest to the necessity of reorganizing health care for patients with CLL. Early administration of effective antiviral compounds and tailored vaccination protocols are warranted.

Platelet function and bleeding in chronic lymphocytic leukemia and mantle cell lymphoma patients on ibrutinib.

BACKGROUND: Therapy with irreversible Bruton's tyrosine kinase inhibitor ibrutinib in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) is associated with bleeding. OBJECTIVES: To propose the predictive markers of such bleeding, as well as mechanisms responsible for decreased bleeding at later therapy stages. PATIENTS/METHODS: We investigate platelet functional activity in 50 CLL and 16 MCL patients on ibrutinib using flow cytometry and light transmission aggregometry. RESULTS: Prior to treatment, both patient groups had decreased platelet counts; impaired aggregation with adenosine diphosphate (ADP); and decreased binding of CD62P, PAC1, and annexin V upon stimulation. Bleeding in patients treated with ibrutinib was observed in 28 (56%) CLL patients, who had decreased aggregation with ADP and platelet count before therapy. Their platelet count on therapy did not change, platelet aggregation with ADP steadily improved, and aggregation with collagen first decreased and then increased in anticorrellation with bleeding. Bleeding in MCL was observed in 10 (62%) patients, who had decreased dense granule release before therapy. ADP and ristocetin induced platelet aggregation in ibrutinib-treated MCL patients increased on therapy, while collagen-induced aggregation evolved similarly to CLL patients. CONCLUSIONS: Our results suggest that ibrutinib-dependent bleeding in CLL patients involves three mechanisms: decreased platelet count (the most important discriminator between bleeding and non-bleeding patients), impaired platelet response to ADP caused by CLL, and inhibition by ibrutinib. Initially, ibrutinib shifts the balance to bleeding, but then it is restored because of the improved response to ADP.

Glycolate oxidase isoforms are distributed between the bundle sheath and mesophyll tissues of maize leaves.

Glycolate oxidase (EC 1.1.3.15) activity was detected both in the bundle sheath (79%) and mesophyll (21%) tissues of maize leaves. Three peaks of glycolate oxidase activity were separated from maize leaves by the linear KCl gradient elution from the DEAE-Toyopearl column. The first peak corresponded to the glycolate oxidase isoenzyme located in the bundle sheath cells, the second peak had a dual location and the third peak was related to the mesophyll fraction. The mesophyll isoenzyme showed higher affinity for glycolate (Km 23 micromol x L(-1)) and a higher pH optimum (7.5-7.6) as compared to the bundle sheath isoenzyme (Km 65 micromol x L(-1), pH optimum 7.3). The bundle sheath isoenzyme was strongly activated by isocitrate and by succinate while the mesophyll isoenzyme was activated by isocitrate only slightly and was inhibited by succinate. It is concluded that although the glycolate oxidase activity is mainly attributed to the bundle sheath, conversion of glycolate to glyoxylate occurs also in the mesophyll tissue of C4 plant leaves.