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The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Purpose: To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL)., Methods: Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group., Results: Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P = .03) and death (r = 0.56, P = .009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04- 0.85]) in the entire cohort., Conclusion: Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL.

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin's lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Objectives: Malignant lymphomas are cancers of the immune system and are characterized by enlarged lymph nodes that typically spread across many different sites. Many different histological subtypes exist, whose diagnosis is typically based on sampling (biopsy) of a single tumor site, whereas total body examinations with computed tomography and positron emission tomography, though not diagnostic, are able to provide a comprehensive picture of the patient. In this work, we exploit a data-driven approach based on multiple-instance learning algorithms and texture analysis features extracted from positron emission tomography, to predict differential diagnosis of the main malignant lymphomas subtypes., Methods: We exploit a multiple-instance learning setting where support vector machines and random forests are used as classifiers both at the level of single VOIs (instances) and at the level of patients (bags). We present results on two datasets comprising patients that suffer from four different types of malignant lymphomas, namely diffuse large B cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, and mantle cell lymphoma., Results: Despite the complexity of the task, experimental results show that, with sufficient data samples, some cancer subtypes, such as the Hodgkin's lymphoma, can be identified from texture information: in particular, we achieve a 97.0% of sensitivity (recall) and a 94.1% of predictive positive value (precision) on a dataset that consists in 60 patients., Conclusions: The presented study indicates that texture analysis features extracted from positron emission tomography, combined with multiple-instance machine learning algorithms, can be discriminating for different malignant lymphomas subtypes., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2019. Published by Elsevier B.V.)

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists. [ABSTRACT FROM AUTHOR]

Introduction: Fertility preservation (FP) and monitoring has considerable relevance in the multidisciplinary approach to cancer patients. In these consensus-based practical recommendations, the scientific societies Fondazione Italiana Linfomi (FIL) and Società Italiana della Riproduzione Umana (SIRU) reviewed the main aspects and identified the optimal paths which aim to preserve and monitor fertility in patients diagnosed with lymphoma at the different phases of the disease and during long-term survivorship. Methods: For the Panel, eleven experts were selected for their expertise in research and clinical practice on onco-fertility and lymphoma. The Panel's activity was supervised by a chairman. A series of rank-ordering key questions were proposed according to their clinical relevance and discussed among the Panel, focusing on patients diagnosed with non-Hodgkin's lymphomas and Hodgkin lymphoma. Agreement among all the Panelists on the content and terminology of the statements was evaluated by a web-based questionnaire according to the Delphi methodology. Results: From the literature review a total of 78 questions or sentences, divided into the 6 areas of interest, were identified. By applying the Gwet's AC, k was: Section 1: 0,934 (Very good); Section 2: 0,958 (Very good); Section 3: 0,863 (Very good); Section 4: 0,649 (Good); Section 5: 0,936 (Very good); Section 6 raw agreement 100%. Two rounds of Delphi allowed to provide the maximum agreement. All statements were newly discussed in a round robin way and confirmed for the drafting of the final recommendations. Discussion: These recommendations would be useful for onco-hematologists, gynecologists, urologists, and general practice physicians who take care of young lymphoma patients to guarantee an evidence-based oncofertility assessment and treatment during the oncologic pathway. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma. Globally, DLBCL is an aggressive disease, requiring an accurate diagnosis and prompt treatment. The diagnosis is often made on biopsy samples of a nodal mass, however, approximately 40% of DLBCL cases arise at extranodal sites. The most common extranodal site is the gastrointestinal tract, however any extranodal area may be primarily involved. Primary urinary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas, whereas secondary involvement of the urinary bladder by a systemic lymphoma is a more common event. Despite being rare, DLBCL is considered to represent the predominant primary urinary bladder lymphoma. The majority of cases reported in the bladder belong to the DLBCL, NOS group, and there are only rare cases of EBV-positive DLBCL, NOS. In this review, we summarize the current knowledge on DLBCL primarily occurring in the urinary bladder, with the aim of increasing clinician and pathologist awareness on this aggressive lymphoma rarely arising in the urinary bladder. Additionally, we focus on those entities which should be taken into consideration in the differential diagnosis, highlighting potential diagnostic pitfalls. [ABSTRACT FROM AUTHOR]

Summary: COVID‐19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA‐HEMA‐COV project (NCT04352556) investigated patterns of seroconversion for SARS‐CoV‐2 IgG in patients with HMs. A total of 237 patients, SARS‐CoV‐2 PCR‐positive with at least one SARS‐CoV‐2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS‐CoV‐2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P = 0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P = 0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment‐mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients. [ABSTRACT FROM AUTHOR]

Doxorubicin is the most effective single agent in the treatment of non‐Hodgkin's lymphoma (NHL). Its use is limited because of the cardiac toxicity primarily in elderly patients (pts) and in pts with history of cardiac disease. Liposomal doxorubicin has been proven to reduce cardiotoxicity. The aim of this retrospective study was the use of nonpeghylated liposomal doxorubicin (NPLD) in term of efficacy, response rate and incidence of cardiac events. We retrospectively collected the experience of 33 Hematological Italian Centers in using NPLD. Nine hundred and forty‐six consecutive pts treated with R‐COMP (doxorubicin was substituted with NPLD, Myocet) were collected. Median age was 74 years, the reasons for use of NPLD were: age (466 pts), cardiac disease (298 pts), uncontrolled hypertension (126 pts), other reasons (56 pts). According to clinicians' evaluation, 49.9% of pts would not have used standard doxorubicin for different situations (age, cardiomyopathy, previous use of doxorubicin, and uncontrolled hypertension). Overall 687 pts (72.6%) obtained a complete remission (CR). About 5% (n = 51) of subjects developed major cardiotoxic events including heart failure (N = 31), ischemic heart disease (N = 16), acute heart attack (N = 3), and acute pulmonary oedema (N = 1). After a median follow‐up of 32 months, 651 pts were alive and the overall survival (OS) was 72%. After a median observation period of 23 months disease free survival (DFS) was 58%. Either in univariate or in multivariate analysis OS and DFS were not significantly affected by age or cardiac disease. Our findings strongly support that including R‐COMP is effective and safe when the population is at high risk of cardiac events and negatively selected. Moreover, the use of this NPLD permitted that about half of our population had the opportunity to receive the best available treatment. [ABSTRACT FROM AUTHOR]

Diffuse large-B cell lymphomas (DLBCL) and follicular lymphomas (FL) are the most represented subtypes among mature B-cell neoplasms and originate from malignant B lymphocytes. Methylation represents one of the major epigenetic mechanisms of gene regulation. Silent information regulator 1 (SIRT1) is a class III lysine-deacetylase playing several functions and considered to be a context-dependent tumor promoter. We present the quantitative methylation, gene expression and tissue distribution of SIRT1 and some key mediators related to lymphoma pathogenesis in B lymphocytes purified from biopsies of follicular hyperplasias, FL and DLBCL. SIRT1 mRNA levels are higher in FL than follicular hyperplasias and DLBCL. B cell lymphoma 6 (BCL6) positively correlates with SIRT1. SIRT1 promoter shows a methylation decrease in the order: follicular hyperplasia – FL – DLBCL. Kruppel-like factor 4 (KLF4), Death-associated protein kinase 1 (DAPK1) and Spastic Paraplegia 20 (SPG20) methylation increase significantly in FL and DLBCL compared to follicular hyperplasias. Gene expression of DAPK1 and SPG20 inversely correlates with their degree of methylation. Our findings evidence a positive correlation between SIRT1 and BCL6 expression increase in FL. SIRT1 methylation decreases in FL and DLBCL accordingly and this parallels the increase of KLF4, DAPK1 and SPG20 methylation. [ABSTRACT FROM AUTHOR]