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Abstract: Rituximab-treated patients with B-cell lymphoma exhibit profound B-cell depletion and impaired vaccine-induced antibody responses. However, it remains uncertain whether recovery of peripheral B-cell counts after rituximab is sufficient to restore effective humoral immunity following booster vaccination. Patients and methods In this prospective, single-center observational study at the Institute of Oncology Ljubljana, adult B-cell lymphoma patients treated with or previously exposed to rituximab received the Comirnaty® mRNA COVID-19 vaccine. Antibody responses to the SARS-CoV-2 spike and nucleoprotein were measured at baseline, 14 days after the second dose, and at 3, 6, 9, and 12 months. A third dose was administered at 6 months. T-cell responses (IFN-γ release) were assessed in patients before and after the primary series and booster dose. Lymphocyte subsets were analysed pre-vaccination. Adverse events and nutritional status were monitored. Results Patients undergoing anti-CD20 therapy showed absent antibody responses. Longer intervals since rituximab correlated with peripheral B-cell repopulation. However, even after reaching normal B-cell counts, patients’ antibody responses after revaccination remained significantly lower than in controls. Conclusions Rituximab is associated with impaired vaccine-induced antibody responses. Despite recovery of peripheral B-cell counts, patients with B-cell lymphoma show reduced humoral responses compared with healthy individuals following booster COVID-19 vaccination.
Keywords: lymphoma, B-cell, rituximab, COVID-19 vaccines
Published in DiRROS: 03.06.2026; Views: 260; Downloads: 88
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Abstract: CAR T cell therapy is a promising immunotherapy for hematologic malignancies, yet early prediction of outcomes and adverse events remains difficult, especially in small real-world cohorts. We retrospectively analyzed 14 adult patients with diffuse large B-cell lymphoma (DLBCL) treated with CAR T cells in Slovenia, assessing IL-6 increase rates and established predictive metrics including EASIX-C, CAR-HEMATOTOX, and IBPS on Day -5 (pre-lymphodepletion) and Day 0 (infusion). Contrary to our expectation, an inverse correlation was observed between the increase rate of IL-6 and the occurrence of severe cytopenias, indicating higher IL-6 increase rate leads to less severe cytopenias. The EASIX-C score showed higher predictive values when calculated on Day 0, contrary to the CAR-HEMATOTOX score, whose higher predictive values were observed on Day -5. The IBPS predictive values showed mixed results when comparing Day -5 to Day 0. We observed 50% response rate and 29% remission rate. The results highlight the utility of predictive scores, with unexpected findings on IL-6 suggesting further study is necessary.
Keywords: CAR T cell therapy, adverse events, diffuse large B-cell lymphoma, hematologic malignancies
Published in DiRROS: 07.04.2026; Views: 248; Downloads: 272
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Keywords: vsebnost vitaminov pri ljudeh, vitamin D, vpliv pomanjkanja na respiratorna obolenja, priporočila
Published in DiRROS: 15.12.2025; Views: 627; Downloads: 434
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Abstract: Radiation-induced lymphopenia (RIL) is associated with an increased risk of death in solid tumors, including rectal cancer. The aim of this study was to determine whether the sequencing of chemotherapy in total neoadjuvant treatment (TNT) for rectal cancer predicts the development of RIL. Patients and methods We analyzed acute hematologic toxicity data from 53 patients who underwent TNT for locally or locoregionally advanced rectal cancer between July 2022 and April 2023. Twenty-eight patients received induction chemotherapy with capecitabine and oxaliplatin [CAPOX], and 25 received consolidation chemotherapy (6 cycles of CAPOX in both groups). The chemoradiation protocol consisted of Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost Radiotherapy (VMAT-SIB RT) up to 48.4 Gy in 22 fractions, concomitantly with capecitabine twice a day (lat. bis in die, BID). The Mann-Whitney U test was performed to compare RIL between the two patient groups. Pelvic bone marrow was contoured as a non-limiting organ-at-risk to assess the received dose, and binary logistic regression was used to determine whether RIL depends on V5Gy~V42Gy or the planning target volume (PTV) size. Results Thirty-four patients (64.2%) developed RIL of any grade, which was not significantly associated with either the induction or consolidation chemotherapy TNT regimen (Wald = 3.159, p = 0.076). No significant differences were found in neutrophil counts or the neutrophil-to-lymphocyte ratio. In the logistic regression model predicting the likelihood of RIL, two variables were statistically significant: V10Gy (Wald = 4.366, p = 0.037) and V30Gy (Wald = 6.084, p = 0.014). These results indicate that V10Gy< 71% and V30Gy< 26.6% may reduce the likelihood of developing RIL. Conclusions In our study, the sequencing of chemotherapy in TNT for rectal cancer did not predict the development of RIL. However, the incidence of RIL may be reduced by applying RT dosimetric constraints to the pelvic bone marrow.
Keywords: radiation-induced lymphopenia, rectal cancer, total neoadjuvant treatment
Published in DiRROS: 26.11.2025; Views: 811; Downloads: 191
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Abstract: Introduction. IgA vasculitis nephritis (IgAVN) manifests in up to 84% of adult patients with IgA vasculitis (IgAV) and is associated with an elevated risk of progression to chronic kidney failure. The underlying pathogenic mechanism of adult IgAVN in leukocytes remain largely uncharacterised. Although natural killer (NK) cells were investigated in paediatric IgAV, their specific role in the pathogenesis of adult IgAV has yet to be elucidated. Methods. RNA sequencing of leukocytes from adult IgAV patients and healthy controls (HC) was performed. NK cells’ cytotoxicity was assessed using calcein-AM stained K562 cells, and exocytosis was measured by LAMP-1/CD107a expression. Intracellular perforin and granzyme B were analyzed via flow cytometry, and cytokine secretion was measured by Luminex xMAP. Interferon-induced genes were validated with qPCR. Results. Principal component analysis (PCA) of leukocyte gene expression profiles distinguished IgAV patients from HC. Pathway enrichment analysis showed differences in patients’ subsets - Interferon signalling Reactome pathway was observed only in sample from patients with skin-limited IgAV (sl-IgAV) and was confirmed by increased expression of interferon-induced genes using qPCR. Only in samples from IgAVN patients enrichment of NK cell-mediated cytotoxicity KEGG pathway was found. NK cells from IgAVN patients showed significantly decreased cytotoxicity compared to samples from sl-IgAV patients (p = 2.53 × 10− 2). The % of CD107a+-NK cells significantly increased after stimulation in HC (p = 9.7 × 10− 3) and in sl-IgAV patient samples (p = 2.21 × 10− 2) while only a minor increase was observed in samples of IgAVN patients. IgAVN patients exhibited a decreased % of perforin+ NK cells compared to HC. Following phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation, a significant reduction in intracellular perforin level was observed in HC (p = 2.53 × 10− 2), but not in IgAVN patients NK cells. Interferon (IFN)-ϒ and macrophage inflammatory protein (MIP)-1β were significantly decreased in NK cell culture supernatants from IgAVN patients (p = 2.64 × 10− 2 and p = 2.65 × 10− 2 respectively). Conclusion. Patients with IgAVN exhibited impaired cytotoxic and immunomodulatory functions of NK cells, along with a marked absence of interferon signaling in PBMCs. Further studies are needed to confirm if discrimination of patient subsets based on leukocyte samples might be of clinical use and if deregulated NK function might contribute to the pathogenesis of nephritis in adult IgAV.
Keywords: immunoglobulin A, IgAVN, IgA vasculitis, RNA sequencing, kidney diseases, immunoglobulins, killer cells, adults
Published in DiRROS: 12.11.2025; Views: 703; Downloads: 350
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