No abstract

Background: Antibody response following SARS-CoV2 vaccination is somewhat defective in chronic lymphocytic leukemia (CLL). Moreover, the correlation between serologic response and status of cellular immunity has been poorly studied. Objective: This study was undertaken to assess humoral immune and cellular responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in CLL. Methods: The presence of the spike antibodies was assessed at a median time of 14 days from the second vaccine dose of SARS-CoV2 in 70 CLL followed-up at a single institution. Results: The antibody response rate (RR) in CLL patients was 58.5%, compared to 100% of 57 healthy controls of the same sex and age (P< 0.0001). Patients treatment-naïve and those in sustained clinical remission after therapy had the highest RR (87.0% and 87.7%, respectively). In contrast, patients on therapy with a pathway inhibitor as monotherapy and those treated with an association of anti-CD20 antibody were unlikely to respond to the SARS-CoV-2 vaccine (52% and 10%, respectively). In multivariate analysis, early Rai stage (OR, 0.19 [0.05-0.79]; P=0.02) and no previous therapy (OR, 0.06[0.02-0.27]; P<0.0001) were found to be independent predictors of vaccination response. An increase in absolute NK cells (i.e., CD16/CD56 positive cells) in patients with a serological response was found following the second dose of vaccine (P=0.02). Conclusions: These results confirm that serological response to the BNT162b2 vaccine in patients with CLL is impaired. A third boosting vaccine dosage should be considered for these patients.

Expression of CD20, evaluated as antibody binding capacity (ABC) (i.e. absolute number of molecules of antibody per cell), was analyzed using flow cytometry on leukemic cells of 93 previously untreated patients, all fulfilling strict criteria of “immunologically typical” (i.e. CD5+, CD23+) B‐cell chronic lymphocytic leukemia (CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life‐expectancy was observed in the low CD20 expression group compared with the high CD20 expression group (p=0.05; relative risk of death, 0.51, 95% confidence interval, 0.24–1.04). Given the correlation between CD20 ABC and mean fluorescence intensity (MFI) of light chain (LC) surface immunoglobulins (Sm Ig) (r=0.481, p<0.0001), as well as the impact of MFI of Sm Ig LC on overall survival (p=0.01; relative risk of death 0.44; 95% confidence interval, 0.10 to 0.76), we tried to verify whether a combination of B‐cell markers, evaluated in a quantitative manner, could have additive prognostic properties. To this purpose we gave a value of 1 or 0 to each B‐cell marker according to whether it was expressed at a low (i.e. CD20 ABC<17.9times103 molecules/cell, MFI of LC Sm Ig<100) or high (i.e. CD20 ABC≥17.9times103 molecules/cell, MFI of LC Sm Ig≥100) level thus allowing patient stratification into two groups with scores of 2 and 0–1, respectively. Survival of patients who scored 2 was significantly longer than that of patients who scored 0–1 (p=0.02; relative risk of death, 0.44; 95% confidence interval, 0.22–0.72). However, when quantitative changes of CD20 antigen and LC Sm Ig expression, either alone or in combination, were simultaneously analyzed in a Cox model which included usual clinico‐hematological features, only absolute peripheral blood lymphocytosis (p=0.0001) and Binet clinical stages (p=0.0001) maintained their prognostic power unmodified. Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B‐cell CLL better, however, they cannot substitute well‐established clinico‐hematological features in the prognostic assessment of B‐CLL patients.

Our data confirm, with acknowledged limitations due to the low number of patients, the effect of PTH on bone marrow-derived progenitor cells emphasizing that, in our cohort, an intermediary PTH level, achieved following specific guidelines, results in an equilibrate balance between different subsets of progenitor cells.

The co-occurrence of BCR-ABL1 fusion and core-binding factor (CBF) rearrangements is uncommonly reported in AML. Although CBF rearrangements carry a favorable prognosis, the coexistence of BCR-ABL1 is associated with aggressive disease suggesting a potential advantage of high-intensity chemotherapy in association with tyrosine kinase inhibitors. Herein, we describe a refractory AML patient harboring BCR-ABL1 fusion and CBFB rearrangement that was successfully treated with a combination of venetoclax and hypomethylating agent.