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Analysis of immune responses in patients with CLL after heterologous COVID-19 vaccination

Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rates following SARS-CoV-2 vaccination. To investigate this observation, a prospective single-institution study was conducted comparing peripheral blood monon...

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Detalles Bibliográficos
Autores principales: Lee, Hye Kyung, Hoechstetter, Manuela A., Buchner, Maike, Pham, Trang Thu, Huh, Jin Won, Müller, Katharina, Zange, Sabine, von Buttlar, Heiner, Girl, Philipp, Wölfel, Roman, Brandmeier, Lisa, Pfeuffer, Lisa, Furth, Priscilla A., Wendtner, Clemens-Martin, Hennighausen, Lothar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9906673/
https://www.ncbi.nlm.nih.gov/pubmed/36630562
http://dx.doi.org/10.1182/bloodadvances.2022008445
Descripción
Sumario:Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rates following SARS-CoV-2 vaccination. To investigate this observation, a prospective single-institution study was conducted comparing peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates following heterologous BNT162b2/ChAdOx1 vaccination of 15 patients with CLL/small lymphocytic lymphoma (SLL). Two-dose antibody response rate was 40%, increasing to 53% after booster. Patients on Bruton tyrosine kinase inhibitor (BTKi) and venetoclax ± anti-CD20 antibody within 12 months of vaccination responded inferiorly compared with those under BTKi alone. The 2-dose–T-cell response rate was 80%, which increased to 93% after the booster dose. Key transcriptional findings were that interferon–mediated signaling activation including activation of the JAK-STAT pathway generally occurred within days of vaccination, but was independent from the magnitude of the antibody response. Increasing counts of IGHV genes were associated with B-cell reconstitution and improved humoral response rate in the vaccinated patients. T-cell responses in patients with CLL appeared independent of treatment status, whereas higher humoral response rate was associated with BTKi treatment and B-cell reconstitution. Boosting was particularly effective when intrinsic immune status was improved by CLL treatment. Limitations included studying a relatively small cohort, with different treatments and vaccination schedules.