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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
COVID-19 in patients with classic and variant hairy cell leukemia
Robert J Kreitman1, Theresa Yu2, Lacey James1
1Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Insights
Patients with Hairy Cell Leukemia (HCL) and its variant (HCLv) had a high COVID-19 infection rate, but most recovered well. Lower B cell counts correlated with poorer antibody response and longer recovery from COVID-19.
Area of Science:
- Hematology
- Infectious Diseases
- Immunology
Background:
- Hairy cell leukemia (HCL) and its variant (HCLv) are B-cell malignancies known to impair humoral immunity.
- Patients with HCL/HCLv are potentially at higher risk for severe outcomes from infections like COVID-19.
Purpose of the Study:
- To prospectively monitor a large cohort of HCL/HCLv patients for COVID-19 infection and outcomes.
- To investigate the relationship between immune markers, HCL/HCLv status, and COVID-19 outcomes.
Main Methods:
- Prospective monitoring of 503 HCL/HCLv patients for COVID-19 using symptom assessment, antibody testing, and PCR/antigen tests.
- Analysis of COVID-19 infection rates, clinical outcomes, and correlation with B cell counts and recent HCL/HCLv treatments.
Main Results:
- 50% of HCL/HCLv patients contracted COVID-19, with most testing positive via PCR or antigen tests.
- Despite immunosuppression and recent treatments, nearly all patients recovered uneventfully, with a low mortality rate (approx. 1%).
- Lower normal B cell counts, often due to HCL or treatment, were associated with reduced spike antibody levels and longer COVID-19 recovery times.
Conclusions:
- COVID-19 outcomes in HCL/HCLv patients are generally favorable, with low mortality and uncommon sequelae.
- The extent of normal B cell depletion significantly impacts the immune response to COVID-19 and the duration of recovery in these patients.
Abstract:
Hairy cell leukemia (HCL), similar to its variant HCLv, is a B-cell malignancy associated with decreased humoral immunity. We prospectively monitored the largest cohort of patients with HCL/HCLv to date (n = 503) for COVID-19 by symptoms, antibody, and polymerase chain reaction (PCR) and/or antigen positivity. Fifty percent (253 of 503) of the patients with HCL/HCLv (238 HCL and 15 HCLv) had evidence of COVID-19, with 210 (83%) testing positive by PCR or rapid-antigen test. Of the 43 patients without positive tests, all had nucleocapsid antibodies indicating COVID-19 exposure, 7 recalled no symptoms, and 36 had mild symptoms. Of the 210 who tested positive, 23, 46, 129, and 12 cases occurred in 2020, 2021, 2022, and 2023, respectively. Among them, 175 began treatment for HCL/HCLv 0.4 to 429 (median, 66) months before, and 132 had their last dose of anti-CD20 monoclonal antibody 0.2 to 229 (median, 63) months before. Two patients died, including a young woman who began rituximab 2 months after first-line cladribine before vaccine availability. Nearly all patients with HCL/HCLv recovered uneventfully from COVID-19 including those without vaccination or those with significant immunosuppression and recent treatment. However, decreased normal B cells from HCL or treatment was associated with lower spike antibody levels as a response to COVID-19 (P = .0094) and longer recovery time (P = .0036). Thus, in a large cohort of patients with HCL/HCLv and in the first to determine relationships between COVID-19 outcome and immune markers, mortality was relatively low (∼1%), sequelae were uncommon, and recovery from COVID-19 was longer if normal B cells were low after recent treatment. The trials are registered at www.clinicaltrials.gov as #NCT01087333 and #NCT04362865.
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