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Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. Methods: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. Results: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07–0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01–0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. Conclusion: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a significant global issue that has major implications for the healthcare system. The mortality rates associated with SARS-CoV-2 infection vary according to the geographical region and are associated with age, comorbidities and vaccination status. Organ damage is caused by the cytokine release syndrome, which plays a crucial role in the course of coronavirus disease 2019 (COVID-19) infection. Innate and adaptive immune system stimulation in patients with COVID-19 results in inappropriate cytokine release. The anti-IL-6 receptor antagonist, tocilizumab, is used in the treatment of connective tissue diseases. The present single-center retrospective study on patients with COVID-19 admitted to hospital between September, 2020 and April, 2022 aimed to identify predictors of mortality and other unfavorable outcomes in patients treated with tocilizumab for COVID-19-associated pneumonia. Demographics, vaccination status against SARS-CoV-2, the Charlson comorbidity index (CCI), laboratory data and chest X-ray scores were recorded upon admission. In total, 174 subjects (121 males; mean age, 62.43±13.47 years) fulfilling the inclusion criteria were included. Among the 174 participants, 58 (33.3%) were intubated. The mortality rate was 35.1%. The non-survivors were older, mostly females, and had a higher CCI score. At the evaluation upon admission, the survivors presented with higher levels of alanine transferase and gamma glutamyl-transferase and with a greater number of platelets (PLTs), while patients that were intubated were also older, mostly females, and had a higher CCI score (P0.05). Age was identified as the only independent factor predicting mortality in the Cox proportional hazards multivariate regression analysis. By performing a sub-analysis regarding sex, it was revealed that the value of PLTs was an independent factor predicting intubation and 90-day mortality in male patients, and the lymphocyte count was the only factor associated with intubation in female patients. On the whole, the data of the present study may be used to identify patient subpopulations responding to treatment with tocilizumab in prospective clinical trials.

Novel coronavirus infection presents with greater severity in individuals with comorbid chronic lung diseases. Bronchiectasis is an illness characterized by permanent enlargement of the airways, presenting with chronic cough and sputum production and vulnerability to lung infections. Bronchiectasis is not a common comorbid disease in patients with COVID-19 disease and bronchiectasis exacerbation rates were decreased during the pandemic. However, COVID-19 disease is associated with worse outcomes in patients with bronchiectasis and patients with bronchiectasis are more susceptible to SARS-CoV-2 infection development. Pseudomonas putida is an opportunistic pathogen, causing infections mostly in immunocompromised hosts and is not a frequent bacterial colonizer in patients with bronchiectasis. This present study reports a rare case of exacerbation of bronchiectasis by Pseudomonas putida complicating COVID-19 disease in an immunocompetent 70-year-old woman. Clinicians should be aware that SARS-CoV-2 infection is probably a precipitating factor of bronchiectasis exacerbation while bronchiectasis is a risk factor for greater severity of SARS-CoV-2 infection.

Coronavirus disease (COVID-19) is an infection caused by the newly detected coronavirus, SARS-CoV-2. The majority of individuals will exhibit mild to moderate illness. Older individuals, and those suffering from co-existing diseases have a greater probability of experiencing a serious illness. Moreover, elderly patients have higher mortality rates than younger patients, especially those who are unvaccinated. Asymptomatic infection is mostly observed in individuals who are younger, as younger patients are more likely to exhibit a stronger immune response to the infection; aging is characterized by the decline immune function. In this article, a rare case of an unvaccinated 97-year-old woman is described who was admitted to Laiko General Hospital due to altered levels of consciousness, hypotension and a hematoma of the thoracic region, and tested positive for SARS-CoV-2 nucleic acid in a nasopharyngeal specimen and positive for IgG antibodies against the SARS-CoV-2 spike protein without a history of consistent manifestations, indicating a past asymptomatic infection.

Background Failure after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for patients with large B-cell B non-Hodgkin lymphoma, especially when it happens early, is an emerging clinical problem. There are no specific recommendations and therefore treatment of these patients remains empiricaI. Immune checkpoint inhibitors are becoming a therapeutic option for these patients. Case report We present a case of a primary mediastinal large B-cell lymphoma who experienced relapse 3.5 months after axicabtagene-ciloleucel therapy and received pembrolizumab. After four cycles of pembrolizumab, complete metabolic response was confirmed. Treatment was discontinued after the sixth cycle due to immune checkpoint inhibitor-related pneumonitis. The disease remains in remission 8 months after the last pembrolizumab dose. We propose mechanisms of action and optimal duration of pembrolizumab treatment in this setting. Finally, we review the existing literature on the sequential administration of CD19-directed CAR T-cell therapy and immune checkpoint inhibitors. Conclusion Immune checkpoint inhibitors are a promising treatment option for patients after failure of CD19-directed CAR-T cell therapy.

The novel time‐limited combinations with the bcl‐2 inhibitor venetoclax can induce deep responses even in CLL cases with unusual and biologically aggressive presentations, like the skin masses of our patient.

Background Lenalidomide refractoriness constitutes an adverse factor of survival in MM as Lenalidomide relapsing/resistant patients were reported to respond difficultly to next treatment line. Lenalidomide is widely administered in doublet, triplet, or quadruplet schemas as first line treatment or relapse and is the only approved drug for maintenance treatment in MM. Almost all MM patients will become at some time point Len refractory. Len resistance definitions and cautious evaluation is still lacking. Aims To update a previous study from our group (ref) assessing Len-dex treated MM patients’ outcomes according to elapsed time until relapse under treatment. Methods 186 patients were studied. 158 Len-Dex treated at any line and 18 receiving maintenance after ASCT, after informed consent was obtained initially. They were separated into 5 groups, including patients (1) with no response within two months (defined as primary resistant MM - PRMM) in the first, (2) progressing under treatment within 6 months from Len initiation in the 2nd (referred as very resistant MM - VRMM), (3) presenting progression under treatment within 7-12 months (Resistant MM - ResMM), (4) initially sensitive (ISMMP), progressing under treatment after more than 12 months and less than 4 years and (5) long-lasting response presenting eventually relapse (RALR) after more than 4 years from Len initiation. Statistical analysis was performed by conventional methods with the SPSS 21 software. Results Of the 158 len-dex-treated, 16 were PRMM, 23 VRMM, 25 ResMM, 70 ISMMP, 24 RALR. Median overall survival after Len (LenOS) was 3 months (as it was in the former analysis) for PRMM patients with 2,4,4, 3,1,2 being in 1st, 2nd, 3rd and > 4th line treatment. Only 5 PRMM patients received next treatment line after len and managed a further time to next treatment of 9 months. VRMM shared a slight increase of one month in survival after Len, 7 months LenOS vs 6 months in the former analysis, while median LenOS in ISMMM was the same (39 months). RALR patients improved their median LenOS to 87 months compared to 64 observed in previous data. The difference observed may be interpreted by the new agents available for MM treatment. LenOS was significantly different between all groups (p Conclusions We confirmed our results that outcomes are very poor for PRMM and VRMM that constitute a minority of patients that probably cannot be rescued at present. Therapeutical efforts and innovation are mandatory for ResMM and ISMMP. Improved outcomes observed in RALR patients are encouraging in the era of novel agents and monoclonal antibodies availability.

A 51-year male patient presented with large skin masses of the chest wall that were pathologically proven to be chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL) with Ki67:70%. The patient was treated with the time-limited Venetoclax/Obinutuzumab combination for 12 cycles and CLL/SLL including the skin component was set in complete remission.

Coronavirus disease (COVID-19) is an infection caused by the newly detected coronavirus, SARS-CoV-2. The majority of individuals will exhibit mild to moderate illness. Older individuals, and those suffering from co-existing diseases have a greater probability of experiencing a serious illness. Moreover, elderly patients have higher mortality rates than younger patients, especially those who are unvaccinated. Asymptomatic infection is mostly observed in individuals who are younger, as younger patients are more likely to exhibit a stronger immune response to the infection; aging is characterized by the decline immune function. In this article, a rare case of an unvaccinated 97-year-old woman is described who was admitted to Laiko General Hospital due to altered levels of consciousness, hypotension and a hematoma of the thoracic region, and tested positive for SARS-CoV-2 nucleic acid in a nasopharyngeal specimen and positive for IgG antibodies against the SARS-CoV-2 spike protein without a history of consistent manifestations, indicating a past asymptomatic infection. © 2021, Spandidos Publications. All rights reserved.

Η οξεία μυελογενής λευχαιμία χαρακτηρίζεται από σημαντική φαινοτυπική και γενετική ετερογένεια. Κύριο χαρακτηριστικό αποτελεί ο πολλαπλασιασμός άωρων κυττάρων της μυελικής σειράς που προοδευτικά εκτοπίζουν τα φυσιολογικά κύτταρα. Χαρακτηρίζεται από μεγάλο αριθμό επαναλαμβανόμενων κυτταρογενετικών και μοριακών βλαβών, καθώς και επιγενετικών τροποποιήσεων, που αντικατοπτρίζουν τον παθοφυσιολογικό ρόλο των επίκτητων σωματικών μεταλλάξεων. Οι πρώτες μελέτες ασθενών με οξεία μυελογενή λευχαιμία κατέδειξαν ότι κατά κανόνα τα λευχαιμικά κύτταρα δεν ήταν ικανά να πολλαπλασιαστούν εκτενώς και ότι ένα υποσύνολο των κυττάρων αποτελούσαν τον παθολογικό κλώνο. Οι μελέτες του DNA ασθενών με NGS, κατέδειξαν την κλωνική εξέλιξη στη de novo οξεία μυελογενή λευχαιμία καθώς και στην υποτροπή. Έχουν αναγνωριστεί διάφορες μεταλλάξεις που έχουν ως αποτέλεσμα να μεταβάλλουν το σήμα μεταγωγής και να ενισχύσουν τον πολλαπλασιασμό των λευχαιμικών κυττάρων και την επιβίωσή τους. Αυτές περιλαμβάνουν μεταλλάξεις στα γονίδια FLT3, RAS και KIT. Οι μεταγραφικοί παράγοντες διαδραματίζουν ουσιαστικό ρόλο στη διαφοροποίηση όλων των κυττάρων συμπεριλαμβανομένων και των αιμοποιητικών. Στο μυελό των οστών, παράγοντες μεταγραφής, όπως RUNX1, CEBPα και PU.1 ελέγχουν βασικά γονίδια ώστε να διατηρείται η φυσιολογική λειτουργία του αιμοποιητικού συστήματος. Γονίδια που κωδικοποιούν παράγοντες που είτε άμεσα ή έμμεσα εμπλέκονται στη μεθυλίωση ή την απομεθυλίωση του DNA, συμπεριλαμβανομένων των TET2, DNMT3A και IDH1 ή IDH2, παρουσιάζουν επαναλαμβανόμενες μεταλλάξεις. Στις αιματολογικές κακοήθειες, οι μεταλλάξεις IDH1 συχνότερα περιλαμβάνουν αντικατάσταση της αργινίνης στη θέση R132 από κυστεΐνη (cysteine, R132C) ή από ιστιδίνη (hystidine, R132H). Στις IDH2 μεταλλάξεις η αργινίνη αντικαθίσταται συνηθέστερα από γλουταμίνη στο υπόλειμμα 140 (Residue, R140Q) και από λυσίνη στο υπόλειμμα 172 (R172K) Οι μεταλλάξεις IDH2-R140 παρουσιάζονται συχνότερα από τις μεταλλάξεις IDH2-R172 και αντιπροσωπεύουν το 80% των μεταλλάξεων IDH2 στην οξεία μυελογενή λευχαιμία. Μεταλλάξεις στα γονίδια IDH1 και IDH2, παρατηρούνται συνήθως σε ασθενείς με καρυοτυπικές βλάβες που τους κατατάσσουν στην κατηγορία του ενδιαμέσου κινδύνου, συμπεριλαμβανομένης της τρισωμίας 8 και του φυσιολογικού καρυότυπου . Μεταλλάξεις στο γονίδιο ΝΡΜ1 εμφανίζονται περίπου στο 1/3 των ασθενών με οξεία μυελογενή λευχαιμία και συνηθέστερα στους ασθενείς με φυσιολογικό καρυότυπο βλαστών και προσδίδουν καλή πρόγνωση. Η αναγνώριση ότι ορισμένες μεταλλάξεις μπορεί να χαθούν ή να αποκτηθούν σε υποτροπή (π.χ FLT3-ITD), ενώ άλλες ανευρίσκονται στη διάγνωση και παραμένουν σταθερές (π.χ. αναδιατάξεις NPM1,CBF), υποδηλώνουν ότι ξεχωριστοί κλωνικοί πληθυσμοί μπορούν να συνυπάρχουν σε ένα δείγμα ασθενούς με οξεία μυελογενή λευχαιμία. Ο σκοπός της μελέτης είναι η αναζήτηση των μεταλλάξεων των γονιδίων FLT3 και NPM1 (και συγκεκριμένα η μετάλλαξη FLT3-ITD και μεταλλάξεις του εξωνίου 12 του NPM1 αντίστοιχα), στους νεοδιαγνωσθέντες ασθενείς με οξεία μυελογενή λευχαιμία, καθώς και μεταλλάξεις στα γονίδια IDH1 και IDH2, προκειμένου να μελετηθεί η συσχέτισή τους με τους ισχύοντες προγνωστικούς παράγοντες, στα ποσοστά ύφεσης, υποτροπής και ολικής επιβίωσης. Σε αυτή την αναδρομική μελέτη των 126 νεοδιαγνωσθέντων ασθενών με οξεία μυελογενή λευχαιμία αξιολογήθηκε η συχνότητα των μεταλλάξεων IDH, η συσχέτισή τους με τα χαρακτηριστικά άλλων ασθενών καθώς και τα καρυοτυπικά και μοριακά δεδομένα και επιπλέον η επίδρασή τους στο RFS και OS. Υπήρξε ίση κατανομή μεταξύ των δύο φύλων. Το 52% των ασθενών ήταν ηλικίας

Background: Failure after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for patients with large B-cell B non-Hodgkin lymphoma, especially when it happens early, is an emerging clinical problem. There are no specific recommendations and therefore treatment of these patients remains empiricaI. Immune checkpoint inhibitors are becoming a therapeutic option for these patients. Case Report: We present a case of a primary mediastinal large B-cell lymphoma who experienced relapse 3.5 months after axicabtageneciloleucel therapy and received pembrolizumab. After four cycles of pembrolizumab, complete metabolic response was confirmed. Treatment was discontinued after the sixth cycle due to immune checkpoint inhibitor-related pneumonitis. The disease remains in remission 8 months after the last pembrolizumab dose. We propose mechanisms of action and optimal duration of pembrolizumab treatment in this setting. Finally, we review the existing literature on the sequential administration of CD19-directed CAR T-cell therapy and immune checkpoint inhibitors. Conclusion: Immune checkpoint inhibitors are a promising treatment option for patients after failure of CD19-directed CAR-T cell therapy. © 2021 International Institute of Anticancer Research. All rights reserved.

Our unique case of Richter's Transformation presenting as leptomeningial infiltration in a CLL patient receiving venetoclax raises questions on whether the drug penetrates the blood-brain barrier and at what extend, especially in reduced doses given for drug-drug interactions. © 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.

Novel coronavirus infection presents with greater severity in individuals with comorbid chronic lung diseases. Bronchiectasis is an illness characterized by permanent enlargement of the airways, presenting with chronic cough and sputum production and vulnerability to lung infections. Bronchiectasis is not a common comorbid disease in patients with COVID-19 disease and bronchiectasis exacerbation rates were decreased during the pandemic. However, COVID-19 disease is associated with worse outcomes in patients with bronchiectasis and patients with bronchiectasis are more susceptible to SARS-CoV-2 infection development. Pseudomonas putida is an opportunistic pathogen, causing infections mostly in immunocompromised hosts and is not a frequent bacterial colonizer in patients with bronchiectasis. This present study reports a rare case of exacerbation of bronchiectasis by Pseudomonas putida complicating COVID-19 disease in an immunocompetent 70-year-old woman. Clinicians should be aware that SARS-CoV-2 infection is probably a precipitating factor of bronchiectasis exacerbation while bronchiectasis is a risk factor for greater severity of SARS-CoV-2 infection.

Background/aim Hematological malignancies are frequently complicated by secondary immunodeficiency (SID). Immunoglobulin replacement with intravenous gamma globulins (IVIg) reduces infection incidence, antibiotics' need and hospitalization days in these patients. Facilitated subcutaneous immunoglobulin replacement (fSCIg) has been studied in primary immunodeficiency patients and is equally efficacious with several advantages (self-administration, same bioavailability, long infusion intervals, fewer adverse drug reactions). fSCIg has been less extensively studied in SID. We present our retrospective single-center data of fSCIg administration to hematological patients with SID, focusing on efficacy and safety issues. Patients and methods Overall, 33 hematological patients with hypogammaglobulinemia were treated with fSCIg according to ESMO 2015 guidelines, between mid-October 2015 and mid-January 2018 in our Department. Results The infection rate was very low (18.1%). Shorter infusion intervals further reduced it. ADRs were rare (9%) and mild (grade 1). fSCIg managed to reduce the everyday nursery/hospital burden of our tertiary hospital. Conclusion fSCIg compares favorably to IVIg replacement in SID patients.