Viral Population Heterogeneity and Fluctuating Mutational Pattern during a Persistent SARS‐CoV‐2 Infection in an Immunocompromised Patient

Literature offers plenty of cases of immunocompromised patients, who develop chronic and severe SARS‐CoV‐2 infections. The aim of this study is to provide further insight into SARS-CoV‐2 evolutionary dynamic taking into exam a subject suffering from follicular lymphoma, who developed a persistent infection for over 7 months. Eight nasopharyngeal swabs were obtained, and were analyses by qRT‐PCR for diagnostic purposes. All of them were considered eligible (Ct < 30) for NGS sequencing. Sequence analysis showed that all sequences matched the B.1.617.2 AY.122 lineage, but they differed by few mutations identifying three genetically similar subpopulations, which evolved during the course of infection, demonstrating that prolonged replication is paralleled with intra‐host virus evolution. These evidences support the hypothesis that SARS‐CoV‐2 adaptive capacities are able to shape a heterogeneous viral population in the context of immunocompromised patients. Spill‐over of viral variants with enhanced transmissibility or immune escape capacities from these subjects is plausible

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Emergency emicolectomy for intestinal primary Aspergillosis in acute myeloid leukemia

ntestinal aspergillosis is an infection with a very high death rate especially in leukemic patients. Here we describe a case of a 46 years old woman with acute myeloid leukemia (LAM M5) who developed intestinal primary aspergillosis. This patient was diagnosed with LAM M5 through bone marrow aspiration and bone biopsy in March 2004. Symptoms of the disease were slight persistent fever, weight loss, asthenia, anemia, thrombocytopenia,and leukocytosis with high number of blasts in peripheral blood. After induction chemotherapy with ICE (Ifosfamide, Carboplatin, Etoposide), she developed neutropenia and high fever without apparent infective foci. She was treated with empiric antibiotic therapy, nevertheless she developed an intense diarrhea and ileo-cecal distention. Diagnostic exams didn’t show signs of a focal lesion. Despite the change in antibiotic treatment and the transfusions of granulocytes and blood cells, the patient developed extremely critical conditions with persistence of neutropenia and abdominal distention. A surgical treatment was decided at the time. We treated the patient with a two steps surgical procedure. The first step was a right abdominal ileostomy followed by improvement of general conditions and then the second step a right colectomy. The histological morphology confirmed necrotizing colitis with Aspergillus ife. At that time , treatment with voriconazole was started. The general conditions of the patient improved rapidly and we were able to treat the patient with other medical anti-leukemic therapies. The patient is now cured and in healthy state. We obtained a good clinical result as only in other few cases described in literature

Multiple Myeloma and Renal Failure

Renal failure (RF) occurs in approximately 20-30% of multiple myeloma (MM) patients at diagnosis and in more than 50% of patients with advanced disease. The pathogenesis of RF is related to the production of monoclonal light chains that can damage either the tubule (myeloma kidney) or the glomeruli (light chain deposition disease or amyloid light-chain amyloidosis). In the past, the prognosis of patients with MM and RF was considered poor due to the limited number of effective and non-nephrotoxic drugs that were available. At present, novel drugs acting both on MM clone and on bone marrow microenvironment have been introduced into clinical practice; among them, bortezomib-containing regimens have proved to be the most effective. High-dose myeloablative therapy followed by autologous stem cell rescue can also be proposed in younger patients with no other relevant comorbidities

UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate

Low-Dose Cyclophosphamide versus Intermediate-High-Dose Cyclophosphamide versus Granulocyte Colony-Stimulating Factor Alone for Stem Cell Mobilization in Multiple Myeloma in the Era of Novel Agents: A Multicenter Retrospective Study

none14: The optimal stem cell (SC) mobilization strategy for patients with multiple myeloma (MM) remains a matter of debate. Possible approaches include low or high doses of cyclophosphamide (Cy), other chemotherapeutic agents, or granulocyte colony-stimulating factor (G-CSF) alone. The scope of the study was to compare low-dose Cy plus G-CSF versus intermediate-high-dose Cy plus G-CSF versus G-CSF alone for SC mobilization in MM, in terms of efficacy and safety. We retrospectively analyzed 422 MM patients undergoing SC mobilization in 6 Italian centers, including 188 patients who received low-dose Cy (LD-Cy group, defined as 2 g/m2), 163 patients who received intermediate-high-dose Cy (HD-Cy group, defined as ≥ 3 g/m2), and 71 patients who received G-CSF alone (G-CSF group). The median peak of circulating CD34+ cells was 77/µL in the LD-Cy group, 92/µL in the HD-Cy group, and 55/µL in the G-CSF group (P = .0001). The median amount of SCs collected was 9.1 × 106/kg, 9.7 × 106/kg, and 5.6 × 106/kg in the 3 groups, respectively (P = .0001). The rate of mobilization failure (defined as failure to collect ≥2 × 106/kg) was 3.7% in the LD-Cy group, 3.4% in the HD-Cy group, and 4.3% in the G-CSF group (P = .9). The target SC dose of at least 4 × 106/kg was reached in 90.4%, 91.1%, and 78.6% of the patients in these 3 groups, respectively (P = .014). The "on demand" use of plerixafor was higher in the G-CSF group (76%) compared with the LD-Cy group (19%) and the HD-Cy group (6%). In multivariate analysis, G-CSF mobilization and previous use of melphalan or radiotherapy were independently associated with failure to collect the target SC dose of ≥4 × 106/kg. No impacts of age, blood counts, or previous treatment with lenalidomide, bortezomib, or carfilzomib were observed. Our results suggest that LD-Cy may be considered for successful SC mobilization in patients with MM.noneZannetti, Beatrice Anna; Saraceni, Francesco; Cellini, Claudia; Fabbri, Elisabetta; Monaco, Federica; Guarini, Attilio; Laszlo, Daniele; Martino, Massimo; Olivieri, Attilio; Imola, Manuela; Tosi, Patrizia; Chiarucci, Martina; Zuffa, Eliana; Lanza, FrancescoZannetti, Beatrice Anna; Saraceni, Francesco; Cellini, Claudia; Fabbri, Elisabetta; Monaco, Federica; Guarini, Attilio; Laszlo, Daniele; Martino, Massimo; Olivieri, Attilio; Imola, Manuela; Tosi, Patrizia; Chiarucci, Martina; Zuffa, Eliana; Lanza, Francesc

Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia after Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Abstract BACKGROUND: Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. METHODS: We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. RESULTS: The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01). CONCLUSIONS: Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. CLINICAL TRIALS REGISTRATION: NCT02088840