COVID-19 vaccination in patients with classic and variant hairy cell leukemia

Blood Neoplasia Pub Date : 2024-08-28 DOI:10.1016/j.bneo.2024.100035

Robert J. Kreitman , Lacey James , Julie Feurtado , Holly Eager , Olena Sierra Ortiz , Mory Gould , Isaac Shpilman , Hong Zhou , Peter D. Burbelo , Jeffrey I. Cohen , Hao-Wei Wang , Constance M. Yuan , Evgeny Arons

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Abstract

Patients with the B-cell malignancy hairy cell leukemia (HCL) and the poorer-prognosis variant HCLv often receive anti-CD20 monoclonal antibodies (mAbs), which kill normal B cells, impairing humoral immunity. We measured COVID-19 antibodies after doses of COVID-19 vaccine in patients with HCL (n = 415) and HCLv (n = 32). After the second COVID-19 vaccine dose, spike antibody level most strongly correlated with normal B-cell levels (r = 0.365, P < .0001), followed by CD4⁺ T-cell count (r = 0.244, P = .0002), and was less related to immunoglobulin G level (r = 0.101, P = .14). Spike antibody also correlated with normal B cells after the third to fifth vaccine doses and with CD4⁺ count after the third dose. Normal B-cells were undetectable in 87% of patients within 6 months after the last dose of anti-CD20 mAb and were lower than in patients at 6 to 12 months (P = .0003), which, in turn, were lower than at 12 to 18 months (P = .0002). Infection with COVID-19 became more common after use of the third vaccine dose; spike antibody levels were higher in patients with prior infection (positive vs negative nucleocapsid antibodies; P < .0001). Spike antibodies decreased faster after ibrutinib or anti-CD20 mAb. We conclude that decreased levels of normal B cells in patients with HCL/HCLv, due to disease and/or anti-CD20 therapy, are associated with lower COVID-19 vaccination efficiency and such patients may not respond well to vaccines. The associated studies were registered at www.ClinicalTrials.gov as #NCT01087333 (HCL/HCLv) and #NCT04362865 (COVID-19).

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为典型和变异毛细胞白血病患者接种 COVID-19 疫苗

摘要B细胞恶性肿瘤毛细胞白血病（HCL）和预后较差的变异型HCLv患者经常接受抗CD20单克隆抗体（mAbs）治疗，这种抗体会杀死正常B细胞，损害体液免疫。我们在HCL（415人）和HCLv（32人）患者注射COVID-19疫苗后测量了COVID-19抗体。第二剂 COVID-19 疫苗接种后，尖峰抗体水平与正常 B 细胞水平的相关性最强（r = 0.365，P < .0001），其次是 CD4+ T 细胞计数（r = 0.244，P = .0002），与免疫球蛋白 G 水平的相关性较小（r = 0.101，P = .14）。尖峰抗体还与第三至第五剂疫苗接种后的正常 B 细胞以及第三剂疫苗接种后的 CD4+ 细胞计数相关。87%的患者在最后一剂抗CD20 mAb后6个月内检测不到正常B细胞，低于6至12个月时的水平（P = .0003），而后者又低于12至18个月时的水平（P = .0002）。使用第三剂疫苗后，COVID-19 感染变得更加常见；之前感染过的患者的尖峰抗体水平更高（核头抗体阳性与阴性；P < .0001）。使用伊布替尼或抗 CD20 mAb 后，尖峰抗体下降更快。我们的结论是，由于疾病和/或抗CD20治疗，HCL/HCLv患者正常B细胞水平下降与COVID-19疫苗接种效率降低有关，这类患者可能对疫苗反应不佳。相关研究已在 www.ClinicalTrials.gov 注册，注册号为 #NCT01087333（HCL/HCLv）和 #NCT04362865（COVID-19）。

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Blood Neoplasia

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