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%).

COVID-19 infection in patients with haematological malignancies: A single-centre survey in the latest Omicron wave in China.

As the COVID-19 variant Omicron surge in Beijing, China, a better understanding of risk factors for adverse outcomes may improve clinical management in patients with haematological malignancies (HM) diagnosed with COVID-19. The study sample includes 412 cases, mainly represented by acute leukaemia, chronic myeloid leukaemia (CML), plasma cell disorders and lymphoma and chronic lymphocytic leukaemia. COVID-19 pneumonia was observed in 10.4% (43/412) of patients, and severe/critical illness was observed in 5.3% (22/412). Among the 86 cases with advanced malignancies, 17.6% (12/86) of patients developed severe/critical COVID-19, which was significantly higher than reported in patients with stable malignancies (9/326, 2.70%, p < 0.001). Similarly, the advanced malignancy cohort had a higher mortality rate (9/86, 10.5% vs. 0/326, 0%, p < 0.001) and a poor 30-day overall survival (OS) compared with the stable malignancy cohort (74.2% vs. 100.0%, p < 0.0001). Overall, nine patients (2.2%) died. The primary cause of death was progressive HM in four patients and a combination of both COVID-19 and HM in five patients. In the multivariable analysis, over 65 years of age, comorbidities and advanced malignancy were correlated with severe/critical COVID-19 in HM patients. This study sheds light on the poor outcomes among COVID-19 HM patients with the leading cause of advanced malignancy.

Chilblain-Like Lesions (CLL) Coinciding With the SARS-CoV-2 Pandemic in Children: A Systematic Review.

Chilblain-like lesions (CLL) coinciding with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection have been described in the literature. Available reviews of the literature suggest that CLL are associated with younger age, an equal sex ratio, negative testing for SARS-CoV-2, and mild to no extracutaneous manifestations (ECM) associated with COVID-19 infection. This systematic review aims to provide a summary of reports of CLL associated with the early SARS-CoV-2 pandemic in children to clarify the prevalence, clinical characteristics, and resolution outcomes of these skin findings. Sixty-nine studies, published between May 2020 and January 2022, met inclusion criteria and were summarized in this review, representing 1,119 cases of CLL. Available data showed a slight male predominance (591/1002, 59%). Mean age was 13 years, ranging from 0 to 18 years. Most cases had no ECM (682/978, 70%). Overall, 70/507 (14%) of patients tested positive for COVID-19 using PCR and/or serology. In the majority the clinical course was benign with 355/415 (86%) of cases resolving, and 97/269 (36%) resolving without any treatment. This comprehensive summary of pediatric CLL suggests these lesions are rarely associated with COVID-19 symptoms or test positivity.

COVID-19 in patients with chronic lymphocytic leukemia: a multicenter analysis by the Czech CLL study group.

Patients with chronic lymphocytic leukemia (CLL) have a high risk of poor outcomes related to coronavirus disease 2019 (COVID-19). This multicenter cohort study evaluated the impact of COVID-19 infection on the population of CLL patients in the Czech Republic. Between March 2020 and May 2021, 341 patients (237 males) with CLL and COVID-19 disease were identified. The median age was 69 years (range 38-91). Out of the 214 (63%) patients with the history of therapy for CLL, 97 (45%) were receiving CLL-directed treatment at diagnosis of COVID-19: 29% Bruton tyrosine kinase inhibitor (BTKi), 16% chemoimmunotherapy (CIT), 11% Bcl-2 inhibitor, and 4% phosphoinositide 3-kinase inhibitor. Regarding the severity of COVID-19, 60% pts required admission to the hospital, 21% pts were admitted to the intensive care unit (ICU), and 12% received invasive mechanical ventilation. The overall case fatality rate was 28%. Major comorbidities, age over 72, male gender, CLL treatment in history, CLL-directed treatment at COVID-19 diagnosis were associated with increased risk of death. Of note, concurrent therapy with BTKi compared to CIT was not associated with better outcome of COVID-19.

Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review.

Importance: Chronic lymphocytic leukemia (CLL), defined by a minimum of 5 × 109/L monoclonal B cells in the blood, affects more than 200 000 people and is associated with approximately 4410 deaths in the US annually. CLL is associated with an immunocompromised state and an increased rate of complications from infections. Observations: At the time of diagnosis, the median age of patients with CLL is 70 years, and an estimated 95% of patients have at least 1 medical comorbidity. Approximately 70% to 80% of patients with CLL are asymptomatic at the time of diagnosis, and one-third will never require treatment for CLL. Prognostic models have been developed to estimate the time to first treatment and the overall survival, but for patients who are asymptomatic, irrespective of disease risk category, clinical observation is the standard of care. Patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with a low neutrophil count, anemia, or thrombocytopenia and/or symptoms of fever, drenching night sweats, and weight loss (B symptoms) should be offered treatment. For these patients, first-line treatment consists of a regimen containing either a covalent Bruton tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax). There is no evidence that starting either class before the other improves outcomes. The covalent BTK inhibitors are typically used indefinitely. Survival rates are approximately 88% at 4 years for acalabrutinib, 94% at 2 years for zanubrutinib, and 78% at 7 years for ibrutinib. Venetoclax is prescribed in combination with obinutuzumab, a monoclonal anti-CD20 antibody, in first-line treatment for 1 year (overall survival, 82% at 5-year follow-up). A noncovalent BTK inhibitor, pitobrutinib, has shown an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax. Phosphoinositide 3'-kinase (PI3K) inhibitors (idelalisib and duvelisib) can be prescribed for disease that progresses with BTK inhibitors and venetoclax, but patients require close monitoring for adverse events such as autoimmune conditions and infections. In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate. The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents. Conclusions and Relevance: More than 200 000 people in the US are living with a CLL diagnosis, and CLL causes approximately 4410 deaths each year in the US. Approximately two-thirds of patients eventually need treatment. Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.

EXPRESSION OF IMMUNOGLOBULIN SEQUENCES HOMOLOGOUS TO ANTI-SARS-CoV-2 ANTIBODIES AND HIV IN CHRONIC LYMPHOCYTIC LEUKEMIA CASES.

BACKGROUND: Identification of epitopes recognized by leukemic B cells could provide insights into the molecular mechanisms of B cell transformation in chronic lymphocytic leukemia (CLL). The aim of this paper was to compare nucleotide sequences of immunoglobulin heavy chain variable region (IGHV) genes in CLL with known sequences directed against antigens of different origins available in public databases. MATERIALS AND METHODS: Analysis was performed in the groups of 412 unselected CLL patients with productive IGHV gene using polymerase chain reaction followed by direct sequencing. RESULTS: Homology between CLL Ig sequences and antibodies directed against autoantigens was found in 12 patients (2.9%), homology between CLL Ig sequences and antiviral antibodies - in 35 patients (8.5%). Most of these sequences belonged to stereotypical clusters. Among the sequences that have homology to antiviral antibodies, the most prevalent were cases homologous with antibodies against HIV (14 cases, 3.4%) and SARS-CoV-2 antigens (10 cases, 2.4%). None of the patients in our cohort was HIV-infected and the study was conducted before the emergence of SARS-CoV-2 virus. CONCLUSIONS: Suggestions could be made about the possible impact of past infection of SARS-CoV-2 virus on the pathogenesis of CLL. In particular, an increase in the proportion of CLL cases with the expression of some stereotyped BCR and/or an increase of CLL risk in the long-term period after SARS-CoV-2 virus infection is not excluded. This assumption needs to be verified by epidemiological data.

Monoclonal B-cell Lymphocytosis - a review of diagnostic criteria, biology, natural history, and clinical management.

Since first described almost two decades ago, there has been significant evolution in our definition and understanding of the biology and implications of monoclonal B-cell lymphocytosis (MBL). This review provides an overview of the definition, classification, biology, and natural history of MBL, mainly focused on the dominant CLL-like phenotype form of MBL. The increasingly recognized implications of MBL with respect to immune dysfunction are discussed, particularly in view of the COVID-19 pandemic, along with management recommendations for MBL in the clinic.

Patients with CLL have a lower risk of death from COVID-19 in the Omicron era.

Previous studies have shown that patients with chronic lymphocytic leukemia (CLL) and coronavirus disease 2019 (COVID-19) have high mortality rates. Infection with the Omicron variant has been described as a milder disease course in the general population. However, the outcome for immunocompromised patients has not previously been reported. In a cohort of patients with CLL tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at hospital test sites in the time periods before and after dominance of the Omicron variant, rates of hospitalizations and intensive care unit admissions declined significantly, whereas 30-day mortality remained as high as 23% in the period with dominance of the Omicron sublineage BA.2 variant. However, for a larger population-based cohort of patients with CLL (including the hospital cohort), 30-day mortality was 2%. Thus, patients with CLL with close hospital contacts and, in particular, those >70 years of age with 1 or more comorbidities should be considered for closer monitoring and preemptive antiviral therapy upon a positive SARS-CoV-2 test.

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.

Chronic Lymphocytic Leukemia Concomitant with COVID 19: A Case Report.

BACKGROUND COVID-19 is a newly emerging disease that is not yet fully understood. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that is easily transmitted from human to human through the respiratory route. Usually, it presents with fever, headache, fatigue accompanied by respiratory symptoms like cough and dyspnea, and other systemic involvements. Chronic lymphocytic leukemia (CLL) is a common lymphoproliferative neoplasm characterized by absolute lymphocytosis and demonstration of clonality unlike other causes of lymphocytosis. Patients with CLL are considered immunocompromised because of impaired humoral immunity (mainly) and cellular immunity. Therefore, they are vulnerable to various infections including COVID-19. Little is known about the COVID-19 infection when it unmasks CLL. CASE REPORT A 49-year-old man with no significant previous illnesses, and an unremarkable family history, presented with a moderate COVID-19 infection. He initially presented to the emergency department with fever and mild shortness of breath. A complete blood count showed a high white blood cell count with absolute lymphocytosis. Flow cytometry revealed the clonality of the lymphocytes confirming the diagnosis of CLL. Despite having CLL, he developed a moderate COVID-19 infection and recovered in a few days. To the best of our knowledge, this is the first report of CLL, which presented with a COVID-19 infection as the initial presentation. CONCLUSIONS Lymphocytosis is an unexpected finding in patients diagnosed with COVID-19 infection and the elevated lymphocytes may be indicative of other conditions. Secondary causes of lymphocytosis like malignancy or other infections should be considered in these cases.