IntroductionEvidence is scant regarding the long-term humoral and cellular responses Q7 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in cancer patients after repeated booster doses. The possibility of T-cell exhaustion following these booster doses in this population has not yet been fully studied and remains uncertain.MethodsIn this single-center prospective observational study, we explored the specific humoral and cellular response to S1 antigen in 36 patients with solid malignancies at baseline, and after the second and third doses of the mRNA-1273 vaccine.ResultsA dual behavior was observed: 24 (66.7%) patients showed partial specific IFN-γ response after the second dose that was further enhanced after the third dose; and 11 (30.5%) already showed an optimal response after the second dose and experienced a marked fall-off of specific IFN-γ production after the third (4 patients negativization), which might suggest T cell exhaustion due to repetitive priming to the same antigen. One (2.8%) patient had persistently negative responses after all three doses. Seroconversion occurred in all patients after the second dose. We then studied circulating exhausted CD8+ T-cells in 4 patients from each of the two response patterns, those with increase and those with decrease in cellular response after the third booster. The patients with decreased cellular response after the booster had a higher expression of PD1+CD8+ and CD57+PD1+CD8+ exhausted T cells compared with those with an increased cellular response both in vivo and in vitro. The proportion of PD1+CD8+ and CD57+PD1+CD8+ exhausted T cells inversely correlated with IFN-γ production.DiscussionOur preliminary data show that the two-dose SARS-CoV-2 vaccine regimen was beneficial in all cancer patients of our study. An additional booster seems to be beneficial in suboptimal vaccine seroconverters, in contrast to maximal responders that might develop exhaustion. Our data should be interpreted with caution given the small sample size and highlight the urgent need to validate our results in other independent and larger cohorts. Altogether, our data support the relevance of immunological functional studies to personalize preventive and treatment decisions in cancer patients.

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients’ demographics. We selected from our records all 18-years or older solid cancer patients under active treatment vaccinated with the complete three-dose schedule mRNA-1273 vaccine whose adverse drug reactions (ADRs)  after each dose were recorded. Medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded. Results: A total of 93 patients met the inclusion criteria. Local ADRs were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic adverse reactions after the third dose, p < 0.001 and between systemic adverse reactions after the second dose and systemic adverse reactions after the third dose, p = 0.001 A significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects was found. Women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion: The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients’ demographics. This retrospective cohort study included patients 18-years or older with solid malignancies receiving active treatment in our hospital who had received the three-dose schedule of the mRNA9 1273 vaccine and whose side effects after each dose were recorded. Patient electronic medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded from the study. Results: A total of 93 patients met the inclusion criteria. Local adverse drug reactions (ADRs) were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic ADRs after the third dose. Cochran-Armitage test showed a statistically significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects. A logistic regression showed that women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion: The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

Rabbit ceruloplasmin (Cp) was purified after solid ammonium sulfate precipitation to 60% final saturation by a two-step column chromatography procedure, utilizing DEAE-Sephadex A-50 and changing the NaCl concentration in the buffer to 0.16 M to achieve the isolation of the protein. The purified Cp was used to prepare antibodies in guinea pigs that were used afterwards to determine the Cp concentration in normal rabbits and in rabbits with an experimentally induced chronic anemia. The molecular weight of rabbit Cp determined by SDS-PAGE was 125,000 and a high molecular weight Cp of 200,000 comprising 8% of the total purified protein was also found. An optical density ratio (610 nm/280 nm) of 0.0475 and a molar extinction coefficient of 7625 were obtained. Copper determinations yielded a value of 0.24% that corresponds to 5 copper atoms per molecule. The staining of Cp following discelectrophoresis in polyacrylamide gels also showed a two band pattern.

Background: Breast cancer is the most common cancer among women worldwide. Most breast cancers are estrogen receptor-positive and epidermal growth factor receptor 2 negative (ER+/HER2-). A small proportion of these cases are metastatic, and cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the mainstay of treatment in this scenario. Evidence supports the existence of differences between the three approved cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in preclinical and clinical settings. However, literature regarding the use of a CDK4/6i in metastatic breast cancer patients (MBC) previously treated with another CDK4/6i is scarce. Methods: A search will be performed on the PubMed, Embase, and Web of Science databases following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. In addition, a manual search of the San Antonio Breast Cancer Conference, American Society of Clinical Oncology annual conference, European Society of Medical Oncology annual conference, and European Society of Medical Oncology Breast annual conference will be conducted. Discussion: To our knowledge, no previous systematic review has evaluated the available evidence regarding the efficacy and safety of CDK4/6i treatment in MBC previously treated with another CDK4/6i. This systematic review and meta-analysis will synthesise existing data on the effectiveness and safety of using a CDK4/6i after prior exposure to another in MBC. It will also identify gaps in the literature for potential future research. The results of this study will focus on multiple audiences including patients, their families, caregivers, and healthcare professionals. These results will be published in a peer-reviewed journal. Systematic review registration: PROSPERO CRD42022330355

e24072 Background: SARS-CoV-2 vaccines efficacy and safety have been tested in phase 3 studies which did not include cancer patients. Information is scarce regarding COVID-19 vaccines safety in this population. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients’ demographics. This cross sectional study included patients 18-years or older with solid malignancies receiving active treatment in Hospital Clínico San Carlos (Madrid, Spain) who had received the three dose schedule of the mRNA9 1273 vaccine. Patient electronic medical records were reviewed retrospectively to collect data between April 19, 2021 and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded. Results: 93 patients met inclusion criteria. 31 patients (33%) were male and 62 patients (66%) were female. Mean age was 61 [SD 8]. 33% of the study population had metastatic disease. The majority of patients (60%) had ECOG 0 whereas 32% and 8% of the population had ECOG 1 and 2 respectively. Most common tumors were breast (33%) and gastrointestinal (17%). Treatment modalities included chemotherapy (37%), targeted therapy (23%), immunotherapy (12%) and combined therapy (28%). Local adverse effects at the site of injection and systemic adverse reactions had different trends, local adverse reactions were reported more frequently after the first and second dose than after the third (42%, 50% and 36% respectively), while systemic adverse reactions were reported less frequently after the first and second dose than after the third (16%, 35% and 53% respectively). Most common systemic adverse effect was fever followed by malaise and myalgia. No grade 4 or 5 adverse events were reported. We found a statistically significant association between sex and systemic adverse reactions after the third dose with a moderate correlation assessed by Cramer’s V. Cochran-Armitage test showed a statistically significant linear trend, p = 0.012, with higher ECOG score associated with a lower proportion of patients suffering from systemic side effects. A logistic regression showed that females had 5.79 times higher odds to exhibit systemic adverse events after the third dose (p = 0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting adverse events (p = 0.016). ECOG scores didn’t show a statistically significant association. Conclusions: mRNA-1273 vaccine shows a tolerable safety profile, which is similar to the non-oncologic population. The likelihood of adverse reactions appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate the safety profile of COVID-19 vaccines in cancer patients.

Background: Human bocavirus (HBoV) is a viral pathogen from the genus Bocaparvovirus (family Parvoviridae, subfamily Parvovirinae) discovered in 2005. Most of available literature is about HBoV in children and adults with hematological malignancies and in otherwise healthy children with respiratory infections. Information regarding infection in the adult population with solid tumors is scarce. Case Report: We report the case of a 51-year-old male with metastatic castration resistant prostate cancer undergoing chemotherapy treatment who presented with fever, dyspnea, dry cough, and pleuritic pain. Imaging techniques showed signs of congestive heart failure. Symptoms, laboratory tests and echocardiography revealed a more probable infectious etiology. Antibiotic therapy was started. A polymerase chain reaction (PCR) test of nasopharyngeal exudate for respiratory viruses was positive for HBoV. The rest of the microbiological tests were negative. Bronchoalveolar lavage (BAL) was performed. Bacterial culture of BAL was negative while respiratory virus PCR confirmed positivity for HBoV. Antibiotic therapy was discontinued. The patient gradually recovered. Conclusions: Emerging infectious diseases are a notorious threat for immunocompromised populations such as solid tumor patients. This case is unique because to our knowledge this is the first case report article of HBoV in a solid tumor patient and because imaging techniques exhibited signs of congestive heart failure that did not correlate with the rest of the tests. It shows that unusual pathogens should be considered when managing serious clinical complications with uncommon presentations in cancer patients. Notable diagnostic efforts should be made to reach a diagnosis in these cases.