| 1. |
- Andersson, Maria, et al.
(författare)
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Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia
- 2023
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Ingår i: Journal of Hematology. - : Elmer Press, Inc.. - 1927-1212 .- 1927-1220. ; 12:4, s. 170-175
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination.Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides.Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors.Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.
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| 2. |
- Lagerlöf, Ingemar, et al.
(författare)
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Limited, But Not Eliminated, Excess Long-Term Morbidity in Stage I-IIA Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Limited-Field Radiotherapy
- 2022
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Ingår i: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 40:13, s. 1487-1496
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Balancing disease control and toxicity from chemotherapy and radiotherapy (RT) when treating early-stage classical Hodgkin lymphoma (cHL) is important. Available data on long-term toxicity after RT for cHL mostly refer to RT techniques no longer in use. We aimed to describe long-term toxicity from modern limited-field (LF)-RT after two or four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). PATIENTS AND METHODS This study included all patients with cHL treated with two or four cycles of ABVD and 30 Gy LF-RT during 1999-2005 in Sweden. Patients (n = 215) and comparators (n = 860), matched for age, gender, and region of residence, were cross-checked against national health registries for malignancies, diseases of the circulatory system (DCS), and diseases of the respiratory system (DRS) from the day of diagnosis of cHL. RESULTS The risk of a malignancy was higher for patients than comparators, hazard ratio (HR) 1.5 (95% CI, 1.0 to 2.4), as was the risk for DCS 1.5 (95% CI, 1.1 to 2.0) and for DRS 2.6 (95% CI, 1.6 to 4.3). The median followup was 16 years (range, 12-19 years). Of individual diagnoses in DCS, only venous thromboembolism was statistically significantly elevated. If the first 6 months (ie, time of active treatment for cHL) were excluded and censoring at relapse of cHL or diagnosis of any malignancy, the increased HR for venous thromboembolism diminished. Most of the excess risk for DRS consisted of asthma, HR 3.5 (95% CI, 1.8 to 6.8). Patients diagnosed with DRS were significantly younger than comparators. CONCLUSION Compared with toxicity from earlier RT techniques, excess morbidity was not eliminated, but lower than previously reported. The elevated risk of DRS was driven by diagnosis of asthma, which could in part be explained by misdiagnosis of persisting pulmonary toxicity.
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| 3. |
- Lagerlöf, Ingemar, et al.
(författare)
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No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy
- 2020
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 188:5, s. 685-691
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Tidskriftsartikel (refereegranskat)abstract
- When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.
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