Multicenter Experience Using Total Lymphoid Irradiation and Antithymocyte Globulin as Conditioning for Allografting in Hematological Malignancies

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day −11 through −1 with ATG at the dose of 1.5 mg/kg/day (from day −11 through −7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects

Studies aimed at protecting and safeguarding the deep water table in the Apulian karst, S Italy

Apulia, the south-eastern sector of Italy, consisting of a elongated peninsula known as the “heel of the Italian boot” for its configuration, is almost entirely karst, due to widespread outcropping of carbonates, which make up the entire structure of the region with a thick sequence of mostly Cretaceous limestones. The deep aquifers in Apulia are subjected to a variety of threats leading to likely pollution, the first one being marine intrusion processes: the high tourist vocation of the area results in the summer months in a very heavy presence along the Apulian coastlines, with a consequent impressive increase in the demand of water. Further, fragility of the karst setting, combined with several other negative actions produced by human activities (soil and water contamination, illegal waste disposal, etc.), are at the origin of many episodes of pollution in the region. Recently, Apulia Region funded a project dedicated to evaluation of the quantity and quality of the groundwater resources, starting from the study and analysis of those karst systems which directly connect the surface with the deep aquifer. This situation occurs in Apulia at two sites: the first in the central sector of the region (Low Murge), and specifically in a polje named Canale di Pirro, whilst the second is located in the southern part of Apulia (Salento). Within the Canale di Pirro polje, excavating a swallow hole known since the 1960’s but never explored in detail, allowed a few years ago to discover a huge cave system, entirely developed in the Cretaceous limestones, which now reaches the water table at depth of -264 meters; diving explorations brought the total depth of the cave down to -324 meters. The cave consists of a series of vertical shafts, rapidly reaching about 100 m below the surface, before developing through a mostly sub-horizontal course, gradually deepening until reaching the final, 100 mt-deep, shaft, which bottom is occupied by the water table. Huge spaces and wide shafts characterize the system, which has become the deepest cave in Apulia, with explorations still ongoing. In Salento, Vora Bosco is the other study site, where the water table is reached at depth of -72 m from the surface, after crossing the whole geological succession, in this case consisting of Quaternary Deposits, Plio-Pleistocene and Miocene calcarenites, before reaching in the very final meters of the cave the Cretaceous bedrock. This contribution illustrates the activities so far carried out during the project, with a particular focus on geology, morphology and structural geology of the cave systems and their surrounding areas, together with hydrogeological research and chemical analyses of the groundwater

Lack of detection of West Nile virus in an islander population of chelonians during a West Nile virus outbreak.

In 2011, several outbreaks of West Nile disease occurred in Sardinia (Italy). The region hosts several chelonian species. Because of the increasing concern on the potential role that ectotherms may play in the ecology of West Nile virus (WNV), in October 2011 blood samples were collected from 41 endemic Sardinian chelonians and tested for the presence of active WNV infection or neutralizing antibodies by real time polymerase chain reaction (RT-PCR) and serumneutralisation, respectively. Neither WNV neutralising antibodies (0%; 95% CI: 0‑8.4%) nor WNV RNA (0%; 95% CI: 0‑6.8%) were found in the tested samples. According to the results of this screening survey, it is unlikely that chelonians are involved in the epidemiology of the 2011 WNV outbreaks in Sardinia

JAK Inhibition with Ruxolitinib in Patients with COVID-19 and Severe Pneumonia: Multicenter Clinical Experience from a Compassionate Use Program in Italy

Jak inhibitors are potent anti-inflammatory drugs that have the potential to dampen the hyperactive inflammatory response associated with severe COVID-19. We reviewed the clinical outcomes of 218 patients with COVID-19 hospitalized for severe pneumonia and treated with ruxolitinib through a compassionate use program. Data on the duration of treatment; outcomes at 4, 7, 14, and 28 days; oxygen support requirements; clinical status; and laboratory parameters were retrospectively collected. Overall, according to the physician evaluation, 66.5% of patients showed improvement at follow-up; of these, 83.5% showed improvement by day 7. Oxygen support status also showed improvement, and by day 7, 21.6% of patients were on ambient air, compared with 1.4% at baseline, which increased to 48.2% by day 28. Significant decreases in C-reactive protein and increases in the lymphocyte total count were already observed by day 4, which seemed to correlate with a positive outcome. At the end of the observation period, 87.2% of patients were alive. No unexpected safety findings were observed, and grade 3/4 adverse events were reported in 6.9% of patients

GITMO REGISTRY STUDY ON ALLOGENEIC TRANSPLANTATION IN PATIENTS AGED OVER 60 FROM 2000 TO 2017. IMPROVEMENTS AND CRITICISMS

Background: Nowadays, allogeneic stem cell transplantation (Allo-SCT) can be offered to patients up to the age of 70-72 years and represents one of the most effective curative treatments for many hematological malignancies. Objectives: The primary objective of the study is to collect data from the allo-SCTs performed in Italy from 2000 to 2017 in patients over 60 years of age to evaluate the changes in safety and efficacy outcomes as well as their distribution and characteristics over time. Study design: The GITMO AlloEld study (ClinicalTrials.gov: NCT04469985) is a retrospective, analysis of the allo-SCTs performed 30 Italian transplant Centers on older patients (≥ 60 years) from 2000 to 2017 (n=1,996). Results: For the purpose of analysis, patients were grouped into three time periods: time A: 2000-2005, n=256 (12%); time B: 2006-2011, n=584 (29%); and time C: 2012-2017, n=1156 (59%). After a median follow-up of 5.6 years, the 5-year Non Relapse Mortality (NRM) remained stable (time A: 32.8%; time B: 36.2%; and time C: 35.0%, p = 0.5); the Overall Survival (OS) improved (time A: 28.4%; time B: 31.8%; and time C: 37.3%, p = 0.012); and the Cumulative Incidence of Relapse (CIR) reduced (time A: 45.3%; time B: 38.2%; time C: 30.0%, p < 0.0001). The 2-year incidence of extensive cGVHD reduced significantly (time A: 17.2%; time B: 15.8%; and time C: 12.2%, p = 0.004). Considering times A and B together (2000-2011), the 2-year NRM was positively correlated to the HCT-CI score; patients with HCT-CI of 0, 1 or 2, or ≥3 had rates of NRM of 25.2%, 33.9%, and 36.1%, respectively, (p < 0.001). Meanwhile, after 2012, the HCT-CI score was not significantlly predictive of NRM. Conclusions: The study shows that the transplant procedure in elderly patients became more effective over time. Relapse incidence remains the major problem and strategies to prevent it are under investigation (e.g. post-transplant maintenance). Today, the selection of patients aged over 60 could be improved by combining HCT-CI and frailty assessments to better predict NRM

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study

Unlabelled: The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome

GITMO Registry Study on Allogeneic Transplantation in Patients Aged ≥60 Years from 2000 to 2017: Improvements and Criticisms

none37: Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.noneMalagola, Michele; Polverelli, Nicola; Rubini, Vicky; Martino, Massimo; Patriarca, Francesca; Bruno, Benedetto; Giaccone, Luisa; Grillo, Giovanni; Bramanti, Stefania; Bernasconi, Paolo; De Gobbi, Marco; Natale, Annalisa; Terruzzi, Elisabetta; Olivieri, Attilio; Chiusolo, Patrizia; Carella, Angelo Michele; Casini, Marco; Nozzoli, Chiara; Mazza, Patrizio; Bassi, Simona; Onida, Francesco; Vacca, Adriana; Falcioni, Sadia; Luppi, Mario; Iori, Anna Paola; Pavone, Vincenzo; Skert, Cristina; Carluccio, Paola; Borghero, Carlo; Proia, Anna; Selleri, Carmine; Sacchi, Nicoletta; Mammoliti, Sonia; Oldani, Elena; Ciceri, Fabio; Russo, Domenico; Bonifazi, FrancescaMalagola, Michele; Polverelli, Nicola; Rubini, Vicky; Martino, Massimo; Patriarca, Francesca; Bruno, Benedetto; Giaccone, Luisa; Grillo, Giovanni; Bramanti, Stefania; Bernasconi, Paolo; De Gobbi, Marco; Natale, Annalisa; Terruzzi, Elisabetta; Olivieri, Attilio; Chiusolo, Patrizia; Carella, Angelo Michele; Casini, Marco; Nozzoli, Chiara; Mazza, Patrizio; Bassi, Simona; Onida, Francesco; Vacca, Adriana; Falcioni, Sadia; Luppi, Mario; Iori, Anna Paola; Pavone, Vincenzo; Skert, Cristina; Carluccio, Paola; Borghero, Carlo; Proia, Anna; Selleri, Carmine; Sacchi, Nicoletta; Mammoliti, Sonia; Oldani, Elena; Ciceri, Fabio; Russo, Domenico; Bonifazi, Francesc

EXPO 1851-2015. Storie e immagini delle grandi esposizioni

EXPO 1851-2015. Storie e immagini delle Grandi Esposizioni è un volume dedicato alla storia delle Esposizioni universali dalla loro nascita ad oggi, diretto dal professor Alberto Abruzzese, sociologo della comunicazione, già docente all’università IULM di Milano. Il volume è curato dal professor Luca Massidda, docente di Sociologia Urbana presso la Scuola di Architettura e Design di Ascoli Piceno, Università di Camerino. L’opera è strutturata in tre sezioni. La prima, dal titolo Storie, analizza l’importanza delle Grandi Esposizioni - da Londra 1851 a Shanghai 2010 - secondo diverse ottiche tematiche (dal lavoro alla scienza, alla tecnologia, all’arte, all’impatto architettonico, alla comunicazione). La seconda sezione, Geografie: le Grandi Esposizioni nel mondo e in Italia ripercorre la storia delle esposizioni secondo un criterio geografico – Europa, Americhe e Asia - dando particolare risalto all’Italia con le Esposizioni di Milano 1906, Torino 1911 e Roma 1942 (mai attuata a causa della guerra). La terza sezione del volume, dal titolo Primo piano: Milano 2015, è dedicata all’Expo attuale, mettendone in luce la genesi, le problematiche progettuali, architettoniche ed espositive, l’importanza economica per Milano e per il sistema-Paese e il significato del tema “Nutrire il Pianeta, energia per la Vita” che costituisce l’asse culturale portante della manifestazione. Il volume raccoglie 42 saggi, tutti firmati da studiosi che si sono già autorevolmente occupati del tema delle Grandi Esposizioni universali. Chiudono infine il volume alcune interviste a personaggi delle istituzioni della cultura sul significato di Expo 2015 e il testo integrale della “Carta di Milano”