Improved outcomes in patients with chronic lymphocytic leukaemia infected during the omicron BA.5 subvariant surge.

Patients with chronic lymphocytic leukaemia (CLL) infected with SARS-CoV-2 are at increased risk of severe COVID-19 and death. The outcomes of CLL patients with COVID-19 during the omicron subvariants and in particular with BA.5 are not fully elucidated. Here, we report the outcomes of 128 CLL patients diagnosed with COVID-19 from December 2021 through November 2022. The hospitalization and 30-day mortality rates were 26.6% (n = 34) and 4.7% (n = 6), respectively. Both hospitalizations and mortality were lower during the outbreaks of the BA.2 and BA.5 subvariants (17.2%, 0% vs. 15.2%, 0%, respectively) compared with the period dominated by the BA.1 subvariant (41.5%, 11.3%).

Clinical features, therapy patterns, outcomes and prognostic factors of solitary plasmacytomas: a report of the Israeli Myeloma Study Group.

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia. In this retrospective multicenter study, 68 SP patients were included. Compared to solitary extramedullary plasmacytoma (SEP), patients with solitary bone plasmacytoma (SBP) were younger (57.3 vs. 70.9 years, p = 0.031), had larger plasmacytoma (median: 5.4 vs. 3 cm, p = 0.007) and higher median involved free light chain level (61 vs. 25.8 mg/L, p = 0.056). 92.6% of patients were treated by radiotherapy and 11.8% received systemic anti-myeloma treatment. With a median follow-up of 42 months, 45.6% of patients progressed (8.8% - recurrent SP, 36.8% - active myeloma). The median PFS was 58 months and the median OS has not been reached (10-year OS: 84.8%). Patients who received also anti-myeloma treatment had longer PFS compared to those who did not (median not reached vs. 48 months, p = 0.056). In conclusion, SBP and SEP appear to be different diseases. Radiotherapy is the cornerstone in the SP treatment. A large prospective trial is needed to evaluate the impact of adding systemic anti-myeloma treatment to local radiotherapy.

Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination.

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to coronavirus disease 2019 (COVID-19) vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard 2-dose vaccination regimen. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL, the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%; n = 12/100) was lower compared with treatment-naïve patients (40.0%; n = 16/40; OR = 4.9, 95% CI 1.9-12.9; P < .001) and patients off-therapy (40.6%; n = 13/32; OR = 5.0, 95% CI 1.8-14.1; P < .001), (P < .001). In patients actively treated with Bruton's tyrosine kinase (BTK) inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n = 9/59, and 7.7%, n = 3/39, respectively). Only 1 of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR = 5.6, 95% CI 2.3-13.8; P < .001) and serum immunoglobulin A levels ≥80 mg/dL (OR = 5.8, 95% CI 2.1-15.9; P < .001). In patients with CLL/SLL who failed to achieve a humoral response after standard 2-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy. This trial was registered at www.clinicaltrials.gov as #NCT04862806.

Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study.

BACKGROUND: Daratumumab (Dara) is generally well tolerated, but is associated with increased risk of infection. METHODS: We investigated hypogammaglobinemia occurrence in different Dara-based regimens. Multiple myeloma (MM) patients were treated with ⩾2 cycles of Dara-based therapy during 2016-2020, mainly for relapsed/refractory disease. Data on patient characteristics, treatment regimens, polyclonal IgG (poly-IgG) and uninvolved free light chain (Un-FLC) levels during treatment, as well as predictors for hypogammaglobinemia and predictors for infections, were evaluated retrospectively. RESULTS: A total of 84 patients, median age 67.2 years, were included. Dara, mainly as ⩾2 line therapy (88.1%, n = 74), was combined with immunomodulating drugs (IMiDs) (53%), proteasome inhibitors (PIs) (15%), IMiDs-PIs (11%), or dexamethasone only (21%). Median treatment duration was 13 months. Median Poly-IgG levels at 0, 2, and 4 months were 7.1 g/l, 4.5 g/l, and 4 g/l, respectively, and remained low throughout treatment. Lower poly-IgG pre-Dara (p = 0.001) and Dara-PIs (±IMiDs) regimen were associated with lower poly-IgG levels at 4 months (p = 0.03). Only patients treated with Dara monotherapy had partial immune reconstitution, reflected by resumption of IgM levels. Most (85%) patients developed ⩾1 infections, mostly grade 1-2 respiratory (76%). A lower poly-IgG level post Dara (RR = 1.137 p = 0.026) predicted increased risk of any infection. Intravenous immunoglobulin (IVIG) was associated with a significant decrease in all infections. CONCLUSION: Relapsed MM patients treated with Dara, often experience persistent hypogammaglobinemia, irrespective of responsiveness to treatment. Infections, especially respiratory, are frequent and apparently related to low Poly-IgG levels. IVIG should be considered for reducing infections in these patients.

Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine in patients with CLL and compared responses with those obtained in age-matched healthy control subjects. Patients received 2 vaccine doses, 21 days apart, and antibody titers were measured by using the Elecsys Anti-SARS-CoV-2 S assay after administration of the second dose. In a total of 167 patients with CLL, the antibody response rate was 39.5%. A comparison between 52 patients with CLL and 52 sex- and aged-matched healthy control subjects revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). The response rate was highest in patients who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients and 16.0% in patients under treatment at the time of vaccination. In patients treated with either Bruton's tyrosine kinase inhibitors or venetoclax ± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%). None of the patients exposed to anti-CD20 antibodies <12 months before vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, female sex, lack of currently active treatment, immunoglobulin G levels ≥550 mg/dL, and immunoglobulin M levels ≥40 mg/dL. In conclusion, antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment. This trial was registered at www.clinicaltrials.gov as #NCT04746092.

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review.

OBJECTIVES: Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting. METHODS: A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations. RESULTS: Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was ≥ 3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P = .03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4 months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6 ± 7.5% and 90.4 ± 4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n = 517) and 2 clinical trials (n = 62) meeting prespecified criteria. CONCLUSIONS: Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.

The impact of a Facebook campaign among mothers on HPV vaccine uptake among their daughters: A randomized field study.

OBJECTIVE: The popularity of social networks provide an incredible opportunity to enhance the impact of preventive medicine programs. We aimed to assess whether a targeted Facebook campaign among mothers may increase the uptake of human Papilloma virus (HPV) immunization among their 8th-grade daughters. METHODS: This field study was conducted among the members of a state-mandated health organization in Israel. Included were all 21,592 members who were mothers to 14 year-old daughters in the 2018-19 school-year. A total of 17,271 (80%) were randomly allocated to the campaign arm and the rest (n=4,321) were selected as a reference group. The Facebook ads addressed issues and concerns regarding HPV-related diseases and HPV vaccine. Main outcome measures were Facebook metrics on exposure to campaign and HPV immunization among eighth grade daughters of the study participants. RESULTS: Between 8/2018-10/2018, Facebook ads were shown 1.8-million times (a reach of 88%). The uptake of HPV vaccine among daughters of women allocated to the campaign arm (55.3%) was similar (p = 0.749) to 55.0% in the control group. The only significant differences between study groups were observed when stratifying by SES level. In the lowest SES quartile, Facebook campaign significantly (p = .02) reduced vaccine uptake (35% vs. 39.0%), with a relative risk of 0.90 (95%CI: 0.82-0.98), while in the second SES quartile, Facebook campaign increased vaccine uptake from 52.6% to 55.8%, with a RR of 1.06 (95%CI,1.00-1.12). Among mothers in higher SES levels, daughters of exposed and unexposed mothers had similar immunization rates. CONCLUSIONS: Facebook campaign may increase the uptake of HPV vaccine among daughters to mothers of medium-to-low SES level, but it may reduce vaccination among lower SES groups.

Cell-to-cell bacterial interactions promoted by drier conditions on soil surfaces.

Bacterial cell-to-cell interactions are in the core of evolutionary and ecological processes in soil and other environments. Under most conditions, natural soils are unsaturated where the fragmented aqueous habitats and thin liquid films confine bacterial cells within small volumes and close proximity for prolonged periods. We report effects of a range of hydration conditions on bacterial cell-level interactions that are marked by plasmid transfer between donor and recipient cells within populations of the soil bacterium Pseudomonas putida Using hydration-controlled sand microcosms, we demonstrate that the frequency of cell-to-cell contacts under prescribed hydration increases with lowering water potential values (i.e., under drier conditions where the aqueous phase shrinks and fragments). These observations were supported using a mechanistic individual-based model for linking macroscopic soil water potential to microscopic distribution of liquid phase and explicit bacterial cell interactions in a simplified porous medium. Model results are in good agreement with observations and inspire confidence in the underlying mechanisms. The study highlights important physical factors that control short-range bacterial cell interactions in soil and on surfaces, specifically, the central role of the aqueous phase in mediating bacterial interactions and conditions that promote genetic information transfer in support of soil microbial diversity.

Epidemiology of oral, salivary gland and pharyngeal cancer in children and adolescents between 1970 and 2011.

OBJECTIVES: The age of oral and pharyngeal cancer patients has reportedly decreased over the last decade, but most of the peer-reviewed literature regarding oral and pharyngeal cancer in individuals 0-19years of age (Y) is limited to specific tumor sites and/or types, or a small number of cases. Our aim is to characterize oral, salivary gland and pharyngeal cancer (OSPC) in 0-19Y in order to improve knowledge of the disease in young individuals. METHODS: Data on OSPC between 1970 and 2011 was taken from the Israel National Cancer Registry, and included patient age, gender, tumor site and tumor type. Data analysis was performed by using IBM SPSS, Winpepi software and Joinpoint Regression Program. alpha<0.05 was deemed statistically significant. RESULTS: A total of 13,863 OSPC cases were diagnosed with 2.6% (N=357) of 0-19Y. The male to female ratio was 1.5:1. The rates of diagnosis decreased between 1991 and 2011 and were not significantly different between the genders. The nasopharynx was the leading tumor site (42.3%) followed by the salivary glands (20.5%), and both were more common in 14-19Y. The tonsils and other pharyngeal sites were common among 0-13Y. The main tumor types were lymphomas (20.7%) and carcinomas (19.9%). CONCLUSIONS: The general characteristics of OSPC remained unchanged over the last four decades. This may imply that environmental factors have not had any effect. Males are affected more than females and might have a genetic predisposition for nasopharyngeal malignancy. Health care providers should be aware of the common sites and tumor types among children and adolescents.