Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 197, Issue 1, Pages 41-51Publisher
WILEY
DOI: 10.1111/bjh.18014
Keywords
CLL; COVID-19; immune response; MBL; vaccines
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Chronic lymphocytic leukaemia (CLL) and monoclonal B-cell lymphocytosis (MBL) patients have poor immune response to COVID-19 vaccines, with most of them failing to produce sufficient antibody levels. The patients' treatment status and reduced immune function are associated with vaccine immunization failure.
Chronic lymphocytic leukaemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-cell lymphocytosis (MBL) patients also have immune impairment. We evaluated humoural and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion [<50 AU/ml SARS-CoV-2 II IgG assay, antibody to spike protein; Abbott Diagnostics)] following each of two vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL patients respectively remained seronegative. There was significant association between post dose two antibody level with pre-vaccination reduced IgM (p < 0.0001), IgG2 (p < 0.035), and IgG3 (p < 0.046), and CLL therapy within 12 months (p < 0.001) in univariate analysis. By multivariate analysis, reduced IgM (p < 0.0002) and active therapy (p < 0.0002) retained significance. Anti-spike protein levels varied widely and were lower in CLL than MBL patients, and both lower than in normal donors. Neutralisation activity showed anti-spike levels <1000 AU/ml were usually negative for both an early viral Glade and the contemporary Delta variant and 72.9% of CLI, and 53.3% of MBI, failed to reach levels >= 1000 AU/ml. In a representative sample, similar to 80% had normal T-cell responses. Failed seroconversion occurred in 36.6% of treatment-naive patients, in 78.1% on therapy, and in 85.7% on ibrutinib.
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