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Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an effective treatment for approximately 40% of relapsed/refractory large B cell lymphomas (LBCL), and early identification of patients at risk for relapse or progression after CAR T-cell therapy represents a clinical need.The authors conducted a single-center prospective study on 47 relapsed/refractory LBCL receiving CAR T-cell therapy to evaluate the prognostic value of baseline and after infusionDeep variation of standardized uptake value (SUV)PET parameters and association of DS and variation of SUVThis is a single-center prospective study on 47 lymphoma patients receiving commercial chimeric antigen receptor T-cell therapy aimed to evaluate the prognostic value of baseline and after infusion

COVID-19 continues to be a relevant issue among patients with haematological malignancies (HM). Vaccines are frequently not effective in subjects on active treatment. In this multicentre retrospective study of Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), we collected data from 91 paucisymptomatic HM patients treated with anti-spike neutralizing monoclonal antibodies (nMoAbs) to determine time to viral clearance, referencing it to the expected value of 28 days from an historical group of untreated paucisymptomatic patients. Secondary endpoints included rate of hospitalization, intensive care unit (ICU) admission, COVID-19 related death and safety. SARS-CoV-2 molecular swab negativity was obtained in 86 patients (95%), with a median time of 18 days (IQR 13-26; p 0.0001). We did not find significant variations according to age, diagnosis, treatment type, vaccination status or nMoAbs type. Rate of hospitalization due to COVID-19 progression was 12% (11/91), with 2 patients (2.2%) requiring ICU admission. With a median follow-up of 2.33 months, the overall mortality was 5.5% (5/91), with 3 deaths due to COVID-19. Side effects were rare and self-limiting. Our data suggest that nMoAbs can limit the detrimental effect of immunosuppressive treatments on COVID-19 clinical progression and time to viral clearance. The original trial was registered at www.clinicaltrials.gov as #NCT04932967.

Summary Patients affected by lymphoid malignancies (LM) are frequently immune‐compromised, suffering increased mortality from COVID‐19. This prospective study evaluated serological and T‐cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B‐ and T‐cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex. Overall, patient seroconversion rate was 64·6%: serological response was lower in those receiving anti‐cancer treatments in the 12 months before vaccination: 55% vs 81·9% (P

Coworking spaces are now widespread in Italy, and coworking is presented as an organisational innovation able to meet the needs of the new self-employed work. But what kind of work is actually performed in these spaces? What conditions and difficulties is it dealing with? How do these work experiences reshape the boundaries between different life times and between work and non-work? And what strategies are implemented by coworkers in their search for a "good job"? The book addresses these questions on the basis of a case study on coworking experiences in the city of Florence, exploring the subjective aspects of this form of work, the intertwining of contents, conditions and meaning of work.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% (P =.262) in auto-HSCT and 50% versus 43% (P =.091) in allo-HSCT. TRM at 2 years was 14% versus 5% (P =.405) in auto-HSCT and 31% versus 25% (P =.301) in allo-HSCT. IRM at 2 years was 14% versus 2% (P =.142) in auto-HSCT and 23% versus 14% (P =.304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS (P

Infection-related mortality (IRM) is a substantial component of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). No scores have been developed to predict IRM before transplantation. Pretransplantation clinical and biochemical data were collected from a study cohort of 607 adult patients undergoing allo-HSCT between January 2009 and February 2017. In a training set of 273 patients, multivariate analysis revealed that age >60 years (P = .003), cytomegalovirus host/donor serostatus different from negative/negative (P

Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.

Infection-related mortality (IRM) still represents a major determinant of non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite the curative potential of allo-HSCT, the profound and prolonged status of immune incompetence following transplantation poses patients at risk for lethal opportunistic infections. This is particularly important in transplants from HLA-mismatched donors. Although numerous studies have investigated the role of pre-transplant clinical variables for the prediction of IRM, very few have focused on biological culprits. This study was aimed at the development of a composite clinico-biological prognostic scoring system for the prediction of early and late IRM after allo-HSCT. A total of 492 consecutive adult patients receiving allo-HSCT for hematological disorders were studied from January 2009 to May 2015. Second transplants were excluded, as well as patients for which pre-transplant biological data were missing. The Receiver Operating Characteristics (ROC) curve analysis defined the optimal cut-offs of pre-transplant biological variables predicting 100-days IRM. All variables were then challenged in multivariate analysis. Based on the value of the coefficients selected in the final multivariate model, a weighted score predicting IRM was elaborated in the training cohort of patients (n=273, from January 2012 to May 2015), and then tested in an internal validation cohort of patients (n=219, from January 2009 to December 2011). The median follow-up was of 31 months (range, 1-85). Acute leukemia was the main indication to transplant, accounting for the 61% (n=309) of patients. Fifty-one percent of patients received an HLA-haploidentical donor graft, 27% a fully HLA-matched (10/10) or a single mismatch (9/10) unrelated donor (MUD) graft, 19% a HLA-identical sibling donor and 3% a cord blood unit. Noticeably, 49% (n=248) patients underwent transplant for advanced diseases. To assess uniformity between the training and validation cohorts, we calculated the incidence of NRM as well as overall survival (OS) and progression-free survival (PFS) in each group. OS at 2 yrs was 53% (95% CI: 47% to 60%) in the training cohort and 46% (95% CI: 40% to 53%) in the validation cohort (P=0.050). PFS at 2 yrs was 23% (95% CI: 16% to 23%) in the training cohort and 17% (95% CI: 12% to 27%) in the validation cohort (P=0.440). The 2-yr incidences of NRM and IRM were 28% (95% CI, 23% to 24%) and 22% (95% CI, 18% to 28%), respectively, in the training cohort and 34% (95% CI: 28% to 40%) and 23% (95% CI: 18% to 29%), respectively, in the validation cohort (P=0.371 and P=0.702). Only four variables were found independent predictors of IRM: age >60 yrs (P=0.003), CMV host/donor serostatus different from negative/negative (P 11.11 points). Considering the entire cohort, the 2-yr IRM was 12% (95% CI: 8% to 17%) for low-risk patients (n=196), 23% (95% CI: 17% to 30%) for intermediate-risk patients (n=175) and 37% (95% CI: 28% to 46%) for high-risk patients (n=108) (P Figure 1 shows IRM according to the 3-tiered prognostic model in the training group (A) and in the validation group (B). Additionally, the 2-yrs OS was significantly different among the 3 groups, being 59% (95% CI: 52% to 67%), 50% (95% CI: 43% to 59%) and 37% (95% CI: 29% to 48%), for low, intermediate and high-risk patients, respectively (P=0.0001). The proposed clinico-biological scoring system is able to predict IRM after allo-HSCT and may foster active surveillance and early pre-emptive antimicrobial strategies in patients at higher risk for infectious complications. Moreover, this score pave the way for the prospective investigation of prophylactic infusions of IgM/IgA-enriched immunoglobulins to reduce IRM after allo-HSCT and to improve its overall outcome. Figure 1 Figure 1. Disclosures Ciceri: MolMed SpA: Consultancy.

Multidrug resistant Gram-negative (MDR-GN) bacteria are responsible for severe infections in immune-compromised hosts. Clinical outcome is often poor, especially in patients undergoing hematopoietic stem cell transplantation (HSCT) with mortality rates exceeding 50%. In patients with a documented pre-transplant MDR-GN bacterial infection, HSCT is usually regarded as a potentially harmful procedure, despite its curative potential. Recently, active surveillance strategies based on rectal swab evaluation have been recommended with the aim of early identification of MDR-GN carriers, although they are not routinely performed in every transplant center. After an Institutional outbreak of K. pneumoniae carbapenemase -producing (KPC-Kp) infections in our Centre in June 2012, we decided to start an Institutional programme of active surveillance. No patient was excluded from HSCT, despite a documented colonization. In this study, we retrospectively analysed the results of the active surveillance programme and the impact of a pre-transplant colonization on HSCT outcomes. From July 2012 to January 2016 (43 months), 362 consecutive patients (254 undergoing allogeneic HSCT (allo-HSCT) and 108 autologous HSCT (auto-HSCT) were examined. All patients had a pre-transplant rectal swab evaluable. Blood cultures were performed at each febrile episode. Neutropenic patients developing fever were treated according to internal antimicrobial guidelines, usually with multiple targeted antimicrobial therapy in case of a previously known MDR-GN bacterial colonization. Median follow-up was of 602 days. Pre-transplant carriers were 8% and 17% in auto-HSCT and allo-HSCT recipients, respectively. Both in auto-HSCT and allo-HSCT, 30% of carriers were colonized by KPC-Kp. Among auto-HSCT, the overall survival (OS) did not significantly differ in carriers versus non-carriers (86% vs 84% at 2 years; P=0.231). Moreover, neither transplant-related mortality (TRM) nor infection-related mortality (IRM) were significantly different among the two groups, being of 0% vs 4% at 100 days (P=0.32) and of 0% vs 2% at 100 days (P= 0.099), respectively. In allo-HSCT, the OS was not significantly influenced by the carrier status nor univariate (43% vs 50% at 2 years; P=0.091) or in multivariate analysis (HR 1.41; P=0.129). Furthermore, TRM and IRM were comparable in MDR-GN bacteria carriers versus non-carriers, being 31% vs 25% at 2 years (P=0.301) and 23% vs 14% at 2 years (P=0.304). A MDR-GN bacterial colonization was not an independent risk factor for TRM and IRM, with an hazard ratio (HRs) of 1.428 (P=0.268) and of 1.69 (P=0.215). Furthermore, we did not observe any significant variation in the incidence of severe acute GvHD when comparing carriers and non-carriers (HR 1.86; P=0.087). In multivariate analysis severe acute GvHD was the only independent factor for a worse OS, TRM and IRM ( HRs of 3.177 (P< 0.001), 7,933 (P< 0.001) and 18,690 (P < 0.001), respectively. We registered a total of 168 Gram-negative bloodstream infections (BSIs) and 41/168 (24%) were due to a MDR bacteria, of which 6/41 in auto-HSCT patients and 35/41 in allo-HSCT recipients. Extended spectrum β-lactamases (ESBL+) E. coli (39%) and KPC-Kp (24%) were most frequently isolated from blood cultures. Thanks to the early initiation of a combined antimicrobial therapy guided by the antimicrobial susceptibly test deriving from rectal swabs in patients developing neutropenic fever, we witnessed a significant reduction in 30-day MDR-GN bacteria-related mortality (0% for auto-HSCT and 17% for allo-HSCT patients). Noticeably, in our Center 30-day KPC-Kp-related mortality was only 30%. Our retrospective single-centre study was able to demonstrate that, both in auto-HSCT and allo-HSCT, a pre-transplant colonization status is not significantly associated with a reduced OS, nor with a reduced TRM and IRM. Moreover, the prompt initiation of an adequate empirical therapy based on information coming from rectal swab is able to reduce MDR-GN bacteria-related mortality and to improve the overall HSCT outcome. Disclosures Ciceri: MolMed SpA: Consultancy.