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Keywords: obinutuzumab; AIHA; ITP; CLL EN obinutuzumab AIHA ITP CLL e1 e4 4 12/21/20 20210101 NES 210101 Obinutuzumab is a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, with enhanced direct cell death and antibody-dependent cell-mediated cytotoxicity.1 Obinutuzumab is FDA-approved for chronic lymphocytic leukaemia (CLL) in combination with chlorambucil, ibrutinib or venetoclax as a first-line treatment.2-4 Similar to rituximab, obinutuzumab induces B-cell depletion and reduced antibody production, granting it the potential to effectively treat antibody-mediated autoimmune phenomena. We report here a retrospective analysis of eight patients with CLL/small lymphocytic lymphoma (SLL) who were treated with single-agent obinutuzumab for autoimmune haemolytic anaemia (AIHA) or immune thrombocytopenia (ITP), from September 2018 to March 2020. Among our patients, the results achieved with obinutuzumab were especially impressive in a patient with ITP, resistant to multiple therapies, including splenectomy and rituximab, who rapidly responded to obinutuzumab. A prospective randomized trial comparing the efficacy of obinutuzumab and rituximab in the treatment of AIHA/ITP in patients with CLL/SLL, as well as the optimal duration of treatment (e.g. short-term obinutuzumab), is warranted. [Extracted from the article]

Background Relatives of patients with chronic lymphocytic leukemia ( CLL) are at increased risk of developing CLL. Familial CLL is defined as more than one case of CLL among blood relatives, a phenomenon reported in approximately 5%-10% of all CLL patients. Objective Given the known predisposition of CLL among Ashkenazi Jews, we studied the features of familial CLL in an Israeli population. Methods This is a retrospective study, in which we reviewed the demographics, clinical characteristics, and outcomes of a total of 332 patients with CLL/small lymphocytic lymphoma. Results Familial CLL was recorded in 41 cases (12.3%) of the patients. The age at diagnosis was younger in patients with familial CLL (by almost 3.5 years). Familial CLL was strongly associated with Ashkenazi Jewish origin. Patients with familial CLL more commonly presented with higher hemoglobin and lower serum β-2-microglobulin levels. No significant differences were detected between sporadic and familial CLL in disease stage, time to treatment, second cancers, or overall survival. Conclusion Familial cases of CLL in an Israeli population show a disproportionate ethnic distribution toward Jews of Ashkenazi origin. The clinical characteristics and the overall outcome are not substantially different from sporadic cases. [ABSTRACT FROM AUTHOR]

Abstract: Automated morphological assessment of peripheral blood slides has become an important modality facilitating characterization and quantification of cells in a uniform, fast and robust manner. In this study, we evaluated the morphological diversity in peripheral blood films of 94 chronic lymphocytic leukemia (CLL) patients using the DM1200 CellaVision automated microscopy system. Aberrant lymphocytes and smudge cells were enumerated and correlated with CLL immunophenotype, chromosomal aberrations and prognostic parameters. Herein, we show that the percentages of aberrant and smudge cells was highly variable between patients and did not correlate with each other. Increased aberrant lymphocytes and fewer smudge cells were associated with an atypical immunophenotype including low expression of CD23, higher levels of FMC7 and bright surface levels of CD20. High fraction of aberrant lymphocytes also was associated with trisomy 12. These cells were predominantly of small/medium size, sometimes with cleft nuclei. No correlation was noted between aberrant or smudge cells and clinical stage, CD38, ZA70 or time to first treatment. Taken together, automated morphological analysis of peripheral blood leukocytes emerged as a powerful and robust tool for the quantitative morphological stratification of CLL. Integration of the automated morphological features discriminates between different CLL phenotypes and distinct chromosomal aberrations. [Copyright &y& Elsevier]

Abstract: Peripheral absolute monocyte count (AMC) has been reported to correlate with clinical outcome in different types of cancers. This association may relate to alteration in circulating monocytic subpopulations and tumor infiltrating macrophages. In this study we evaluated the clinical significance of peripheral AMC in 80 treatment naive patients with CLL. Measurement of AMC was based on direct morphological enumeration, due to our findings that complete blood count data may yield incorrect monocytes enumeration values in CLL. The median AMC in patients with CLL was within normal limits, however the AMC range exceeded the values of healthy individuals. The AMC trichotomized patients into 3 distinct sub-groups with different characteristics and outcomes. High AMC patients were younger and had higher absolute lymphocytes count, while patients with low AMC had prominent immune dysregulation (lower serum IgA levels, susceptibility to infections and a tendency for positive direct anti-globulin test). The low and high AMC patients had a shorter time to treatment compared to the intermediates AMC subgroups, whereas low AMC was associated with increased mortality caused by infectious complications. In conclusion, AMC quantification during the disease course classifies CLL patients into subgroups with unique clinical features and outcomes. [Copyright &y& Elsevier]