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Isatuximab, a novel anti‐CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa‐Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real‐world efficacy and safety are poorly reported. In this Italian multicenter real‐life observational retrospective study, efficacy and safety of the Isa‐Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1‐year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa‐Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1‐year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa‐Kd as an effective treatment option for RRMM with a manageable safety profile even in real‐life settings. [ABSTRACT FROM AUTHOR]

Background: Viral reactivations are frequent in hematologial patients due to their cancer‐related and drug‐induced immunosuppressive status. Daratumumab, an anti‐CD38 monoclonal antibody, is used for multiple myeloma (MM) treatment, and causes immunosuppression by targeting CD38‐expressing normal lymphocytes. In this single‐center two‐arm real‐life experience, we evaluated incidence of cytomegalovirus (CMV) reactivation in MM patients treated with daratumumab‐based regimens as first‐ or second‐line therapy. Methods: A total of 101 consecutive MM patients were included in this study and were divided into two cohorts: daratumumab and nondaratumumab‐based (control) regimens. Patients treated with >2 lines of therapies were excluded to reduce the confounding factor of multi‐treated cases. Primary endpoint was the CMV reactivation rate. Results: CMV reactivation rate was significantly higher in the daratumumab cohort compared to control group (33% vs. 4%; p < 0.001), also with higher CMV‐DNA levels (>1000 UI/mL in 12% of cases; p < 0.05). However, only one subject developed a CMV disease with severe pneumonia, while 12% of patients were successfully treated with preemptive therapy with valganciclovir. No subjects in the control cohort required anti‐CMV agents (p = 0.02). Conclusion: Our single‐center retrospective experience showed that daratumumab might significantly increase the risk of CMV reactivation in MM, while currently underestimated and related to morbility and mortality in MM patients under treatments. However, further validation on larger and prospective clinical trials are required. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a patient with refractory multiple myeloma who developed psoriasis as a side effect of lenalidomide treatment. The patient was successfully treated with narrowband ultraviolet B phototherapy (NB-UVB) without discontinuing the lenalidomide. The article highlights the efficacy and safety of NB-UVB in managing lenalidomide-induced psoriasis and suggests that NB-UVB can be considered as a therapeutic option for psoriasis secondary to anti-multiple myeloma agents. However, further validation through larger prospective trials is needed. [Extracted from the article]

Infections caused by antibiotic-resistant bacteria represent a serious threat to global public health. Recently, due to its increased resistance to carbapenems and β-lactams, Klebsiella pneumoniae has become one of the main causes of septicemia, pneumonia, and urinary tract infections. It is crucial to take immediate action and implement effective measures to prevent further spread of this issue. This study aims to report the prevalence and antibiotic resistance rates of K. pneumoniae strains isolated from clinical specimens from 2015 to 2020 at the University Hospital of Salerno, Italy. More than 3,800 isolates were collected from urine cultures, blood cultures, respiratory samples, and others. K. pneumoniae isolates showed broad resistance to penicillin and cephalosporins, and increased susceptibility to fosfomycin and gentamicin. Extended spectrum beta-lactamase (ESBL) isolates accounted for 20–22%. A high percentage of strains tested were resistant to carbapenems, with an average of 40% to meropenem and 44% to ertapenem. The production of ESBLs and resistance to carbapenems is one of the major public health problems. Constant monitoring of drug-resistant isolates is crucial for developing practical approaches in implementing antimicrobial therapy and reducing the spread of K. pneumoniae in nosocomial environments. [ABSTRACT FROM AUTHOR]

Introduction: Fine needle aspiration cytology (FNAC) combined with rapid on‐site evaluation (ROSE) and ancillary techniques is an accurate diagnostic tool for many pathologies. However, in some cases, it may not be sufficient for actionable diagnoses or molecular testing, especially for cases that require large immunohistochemical panels or cases in which histological features are mandatory for the diagnosis. Core needle biopsy (CNB), on the contrary, provides samples that are suitable for histological features and sufficient for all ancillary studies. However, CNB is often performed by radiologists or clinicians without the direct participation of cytopathologists, which can lead to missed or delayed diagnoses. This study reports on the experience of combining FNAC and CNB performed in one setting by cytopathologists. The aim was to evaluate the impact of CNB on FNAC and the diagnostic efficiency of the combined procedures. Materials and Methods: One hundred forty‐two FNAC and CNB procedures performed in the same setting over a period of 2 years were analysed. The FNAC diagnoses were compared and integrated with the subsequent CNB diagnoses. The impact of CNB was categorized as follows: non‐contributory, in cases of inadequate samples; confirmed, when the CNB and FNAC diagnoses were the same; improved, when the CNB diagnosis was consistent with the FNAC diagnosis and further specified the corresponding entity; allowed, when CNB produced a diagnosis that could not be reached by FNAC; changed, when the CNB changed the previous FNAC diagnosis. Results: CNB confirmed the FNAC diagnosis in 40.1% of cases (n = 57/142). CNB improved the FNAC diagnosis in 47.2% of cases (n = 67/142). CNB allowed a diagnosis that could not be performed on FNAC in 2.1% of cases (n = 3/142). CNB changed a previous FNAC diagnosis in 2.1% of cases (n = 3/142). CNB was non‐contributory in 8.4% of cases (n = 12/142). CNB produced a positive impact on the whole diagnostic procedure in 51.4% of total cases (n = 73/142). The combined FNAC and CNB resulted in actionable diagnoses in 91.5% of all cases (n = 130/142). A complete molecular assessment was successfully performed in 14.7% of cases (n = 21/142) utilizing either FNAC or CNB material. Conclusions: The combined use of FNAC and CNB in one setting improves the diagnostic accuracy of both procedures. This approach exploits the advantages of each procedure, enhancing the accuracy of the final diagnosis. [ABSTRACT FROM AUTHOR]

Background: Splicing modifications, genomic instability, and hypomethylation are central mechanisms promoting myelodysplasia and acute myeloid leukemia (AML). In this real-life retrospective study, to elucidate pathophysiology of clonal hemopoiesis in hematological malignancies, we investigated clinical significance of mutations in leukemia-related genes of known pathogenetic significance and of variants of uncertain clinical significance (VUS) in a cohort of patients with MDS and AML. Methods: A total of 59 consecutive subjects diagnosed with MDS, 48 with AML, and 17 with clonal cytopenia with unknown significance were screened for somatic mutations in AML-related genes by next-generation sequencing. Results: We showed that TET2, SETBP1, ASXL1, EZH2, RUNX1, SRSF2, DNMT3A, and IDH1/2 were commonly mutated. MDS patients also showed a high genetic complexity, especially for SETBP1. Moreover, the presence of SETBP1 wild-type or two or more simultaneous VUS variants identified a subgroup of AML and MDS patients with better outcome, while the presence of single SETBP1 VUS variant was related to a worse prognosis, regardless TET2 mutational status. Conclusions: In conclusions, we linked both pathogenic and VUS variants in AML-related genes to clonal hematopoiesis; therefore, we proposed to consider those variants as prognostic markers in leukemia and myelodysplasia. However, further studies in larger prospective cohorts are required to validate our results. [ABSTRACT FROM AUTHOR]

Background: Current chronic lymphocytic leukemia (CLL) International Prognostic Index (IPI) stratifies patients based on clinical, molecular, and biochemical features; however, B‐cell markers also influence CLL outcomes. Here, prognostic roles of CD11c, CD38, and CD49d were first evaluated, and then an immunophenotypic score was combined with CLL‐IPI for risk stratification of CLL patients. Methods: A total of 171 CLL subjects were included, and surface marker expression was assessed by flow cytometry. Levels ≥30% were chosen as cut‐off of positivity to a marker; then values of 1 (for CD11c and CD38) or 3 (for CD49d) were assigned and scores determined for each patient's clone immunophenotype. Results: CD49d positivity was significantly associated with simultaneous expression of CD11c and/or CD38, unmutated IGHV status, and higher β2‐microglobulin levels compared to those with CD49d negativity. Moreover, CD49d+ patients experienced a shorter progression‐free survival and time to treatment. When the immunophenotypic score was combined with CLL‐IPI, patients with high‐risk immunophenotype had a significantly lower time‐to‐treatment regardless CLL‐IPI. Conclusions: Our results suggested clinical utility of an integrated prognostic score for better risk stratification of CLL patients. These results require further validation in prospective larger studies. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma is associated with immunosuppression and human herpesvirus 8 infection, while rarely described in myeloid malignancies. Here, we illustrate a rare case of chronic myeloid leukemia treated with imatinib, a tyrosine kinase inhibitor, who developed a human herpesvirus 8‐related Kaposi's sarcoma. [ABSTRACT FROM AUTHOR]

Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60- 90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitarythyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low- T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. [ABSTRACT FROM AUTHOR]

An alemtuzumab-based experimental immunosuppressive treatment (IST) regimen was investigated in 35 patients with severe aplastic anaemia (SAA), pure red cell (PRCA) or pure white cell aplasia (PWCA). Alemtuzumab total dose was 73–103 mg s.c., followed by cyclosporine. No serious toxicity due to the regimen was observed. Adverse events were clinically irrelevant; infectious events were rare. The total response rate was 58%, 84% and 100% in SAA, PRCA and PWCA, respectively, with corresponding 6 months cumulative response probabilities of 84%, 84% and 100%. Subcutaneous alemtuzumab is a feasible and sufficiently safe IST regimen for patients suffering from immune-mediated marrow failures. [ABSTRACT FROM AUTHOR]