Effective Neutralizing Antibody Response Against SARS-CoV-2 Virus and Its Omicron BA.1 Variant in Fully Vaccinated Hematological Patients.

SARS-CoV-2 and its variants cause CoronaVIrus Disease 19 (COVID-19), a pandemic disease. Hematological malignancies increase susceptibility to severe COVID-19 due to immunosuppression. Anti-SARS-CoV-2 neutralizing antibodies protect against severe COVID-19. This retrospective real-life study aimed to evaluate seropositivity and neutralizing antibody rates against SARS-CoV-2 and its Omicron BA.1 variant in hematological patients. A total of 106 patients with different hematologic malignancies, who have mostly received three or more vaccine doses (73%), were included in this study. Serum was collected between May and June 2022. The primary endpoint was anti-SARS-CoV-2 antibody response against ancestral (wild type; wt) and Omicron BA.1 virus, defined as a neutralizing antibody titer ≥ 1:10. Adequate neutralizing antibody response was observed in 75 (71%) and 87 (82%) of patients for wt and Omicron BA.1 variants, respectively.However, patients with B-cell lymphoproliferative disorders and/or those treated with anti-CD20 monoclonal antibodies in the prior 12 months showed a lower seropositivity rate compared to other patients against both Omicron BA.1 variant (73% vs 91%; P = 0.02) and wt virus (64% vs 78%; P = 0.16). Our real-life experience confirmed that full vaccination against SARS-CoV-2 induces adequate neutralizing antibody protection for both the wt virus and Omicron BA.1 variants, even in hematological frail patients. However, protective measures should be maintained in hematological patients, especially those with B-cell lymphoproliferative diseases treated with anti-CD20 monoclonal antibodies, because these subjects could have a reduced neutralizing antibody production.

Subclones with variants of uncertain clinical significance might contribute to ineffective hemopoiesis and leukemia predisposition.

BACKGROUND: Splicing modifications, genomic instability, and hypomethylation are central mechanisms promoting myelodysplasia and acute myeloid leukemia (AML). In this real-life retrospective study, to elucidate pathophysiology of clonal hemopoiesis in hematological malignancies, we investigated clinical significance of mutations in leukemia-related genes of known pathogenetic significance and of variants of uncertain clinical significance (VUS) in a cohort of patients with MDS and AML. METHODS: A total of 59 consecutive subjects diagnosed with MDS, 48 with AML, and 17 with clonal cytopenia with unknown significance were screened for somatic mutations in AML-related genes by next-generation sequencing. RESULTS: We showed that TET2, SETBP1, ASXL1, EZH2, RUNX1, SRSF2, DNMT3A, and IDH1/2 were commonly mutated. MDS patients also showed a high genetic complexity, especially for SETBP1. Moreover, the presence of SETBP1 wild-type or two or more simultaneous VUS variants identified a subgroup of AML and MDS patients with better outcome, while the presence of single SETBP1 VUS variant was related to a worse prognosis, regardless TET2 mutational status. CONCLUSIONS: In conclusions, we linked both pathogenic and VUS variants in AML-related genes to clonal hematopoiesis; therefore, we proposed to consider those variants as prognostic markers in leukemia and myelodysplasia. However, further studies in larger prospective cohorts are required to validate our results.

Chromosomal anomalies in early spontaneous abortions: interphase FISH analysis on 855 FFPE first trimester abortions.

OBJECTIVE: Cytogenetic analysis of spontaneous abortuses presents at least two main challenges, cell culture failure, and excess of normal female karyotypes related to maternal cell contamination (MCC). Molecular cytogenetic techniques using uncultured cell suspension overcome cell culture failure, but do not resolve MCC at all. The aim of the present study is to demonstrate that interphase fluorescence in situ hybridization (FISH) on routine formalin-fixed paraffin embedded (FFPE) abortive materials is an efficient method to identify chromosomal anomalies in abortuses and to detect MCC. METHOD: Interphase FISH with a panel of eight probes was applied on 855 FFPE consecutive early spontaneous abortions. RESULTS: Male/female ratio was 0.88 in the complete sample, 0.9 in the group of negative FISH result, and 0.8 in the group with abnormal FISH results, suggesting that no gender predominance was present in our data. The aneuploidy rate was 50.3%. Autosomal trisomies were 60%, polyploidies 23.2%, and X monosomy 14%. Chromosomal mosaicism was discovered in 1.9% with six cases of confined placental mosaicism. CONCLUSION: FISH on FFPE abortion materials appears to be a successful approach to detect chromosomal anomalies in abortions. Moreover, the preservation of the tissue morphology allows the analysis of only the fetal cells, making the presence of maternal tissues irrelevant.