The proposed research focuses on the museum context of the city of Turin (Italy), within an ongoing framework agreement between the Politecnico di Torino and the Museum of Oriental Art (MAO). It aims ...at the construction of a model for the management of the workflow that includes the digital survey, the 3D virtual modelling and the digital fabrication of the tactile models of the artworks and the exhibition spaces. The paper starts with an overview on the methods of conservation and dissemination of cultural and architectural heritage, on the accessibility of museums and on tactile perception and graphics. It presents the first outcomes of the designed workflow with a special focus on the digital fabrication experiments on the vaulted system of the atrium of Palazzo Mazzonis (MAO home). The founding idea is that tactile exploration of artifacts helps the visitor engagement, making the museum experience more educationally incisive and more inclusive, in a “Design for All” perspective.
The GIMEMA LAL1509 protocol, designed for adult (≥18-60 years) de novo Ph+ acute lymphoblastic leukemia patients, was based on a dasatinib plus steroids induction - with central nervous system ...prophylaxis - followed by dasatinib alone in patients in complete molecular response or chemotherapy and/or allogeneic transplantation in patients not reaching a complete molecular response. Sixty patients (median age 41.9 years) were enrolled: 33 were p190+, 18 p210+ and 9 p190/p210+. At the end of induction (day +85), 58 patients (97%) achieved a complete hematologic remission. No deaths in induction were recorded. Eleven patients (18.3%) obtained a complete molecular response. Among non-complete molecular responders (n=47), 22 underwent an allogeneic transplant. Seventeen hematologic relapses occurred (median 7 months, range 3-40.1), 13 during consolidation and 4 post-transplant. ABL1 mutations (5 T315I, 3 V299L, 1 E281K and 1 G254E) were found in 10/13 relapsed cases. With a median follow-up of 57.4 months (range: 4.2-75.6), overall survival and disease-free survival are 56.3% and 47.2%. A better diseasefree survival was observed in patients who obtained a molecular response at day +85 compared to cases who did not. The presence of additional copy number aberrations - IKZF1 plus CDKN2A/B and/or PAX5 deletions - was the most important unfavorable prognostic factor on overall and disease-free survival (p=0.005 and p=0.0008). This study shows that in adult Ph+ ALL long-term survivals can be achieved with a total-therapy strategy based on a chemo-free induction and, in complete molecular responders, also without further systemic chemotherapy. Finally, the screening of additional copy number aberrations should be included in the diagnostic work-up. EudraCT 2010-019119-39.
In the GIMEMA LAL 0904 protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with ...imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Fifty-one patients (median age 45.9 years) were enrolled in the final sequential protocol. At the end of induction (day +50), 96% of evaluable patients (n=49) achieved a complete hematologic remission; after consolidation, all were in complete hematologic remission. No deaths in induction were recorded. Overall survival and disease-free survival at 60 months are 48.8% and 45.8%, respectively. At day +50 (end of imatinib induction), a more than 1.3 log-reduction of BCR-ABL1 levels was associated with a significantly longer disease-free survival (55.6%, 95%CI: 39.0-79.3 vs. 20%, 95%CI: 5.8-69.1; P=0.03), overall survival (59.1%, 95%CI: 42.3-82.6 vs. 20%, 95%CI: 5.8-69.1; P=0.02) and lower incidence of relapse (20.5%, 95%CI: 7.2-38.6 vs. 60.0%, 95%CI: 21.6-84.3; P=0.01). Mean BCR-ABL1 levels remained significantly higher in patients who subsequently relapsed. Finally, BCR-ABL1
patients showed a significantly faster molecular response than BCR-ABL1
patients (P=0.023). Though the study was not powered to evaluate the role of allogeneic stem cell transplant, allografting positively impacted on both overall and disease-free survival. In conclusion, a sequential approach with imatinib alone in induction, consolidated by chemotherapy plus imatinib followed by a stem cell transplant is a feasible, well-tolerated and effective strategy for adult Philadelphia positive acute lymphoblastic leukemia, leading to the best long-term survival rates so far reported. (clinicaltrials.gov identifier: 00458848).
Caring for a child with an acute/life threatening disease exposes parents to multiple stressors and challenges, resulting in a physical and psychological burden. Parents experience many ...health-related issues and worries that often remain underestimated. The aims of the study were: (a) to explore the associations between needs/disease-related issues and burden in parents of children with leukemia or Hodgkin’s disease; (b) to estimate predictors of parents’ burden using a stepwise linear regression analysis. Children (N = 33) followed an active therapy protocol (48.5%), or they were off therapy (51.5%). Forty-four parents completed surveys on caregiver burden levels and needs to cope with the child’s illness. Parental factors impacting burden (personal resources, loss of control, depression) and child’s quality of life (QoL) were also assessed. Among the needs, information about the illness/resources were the most urgently expressed by parents, followed by reassurance against fears for the child’s development and future well-being. Parents reported severe (27.3%) and moderate (22.7%) burden, with a higher percentage of caregivers with severe burden in the off-therapy phase (18.2%) than in the active-therapy phase (9.1%). The child’s decreased physical QoL and parent’s loss of control predicted higher levels of burden. The implications for supportive interventions aimed at responding to parental needs and preventing caregiver burden are discussed.
Aberrant DNA methylation is a key pathological mechanism in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and provides rationale for the clinical development of hypomethylating ...agents (HMAs) for the treatment of these diseases. One HMA, azacitidine (Vidaza®, Celgene Corp.), has demonstrated improved survival versus conventional care regimens in patients with intermediate-2/high-risk MDS and AML (20-30% blasts) and has a favorable tolerability profile. Emerging evidence indicates that azacitidine can have an immunomodulatory effect by, for example, increasing functional regulatory T-cell (Treg) numbers and killer-cell-immunoglobulin-like receptor expression. Allogeneic hematopoietic progenitor cell transplantation (allo HPCT) is the only potentially curative treatment approach in patients with advanced MDS or AML. Unfortunately, allo HPCT in these settings is limited because most patients are ineligible due to age/comorbidities, or are at a high risk of treatment failure due to disease relapse. Recent studies have shown that azacitidine after allo HPCT increases Treg numbers while inducing a cytotoxic CD8+ T-cell response, suggesting a potential mechanism for augmenting the graft-versus-leukemia (GvL) effect without increasing graft-versushost- disease (GVHD). In patients at a high risk of relapse following allo HPCT, pre-emptive azacitidine may help prevent/delay relapse. For patients who have relapsed following allo HPCT, azacitidine may be a salvage therapy option, either as monotherapy or in combination with donor lymphocyte infusions (DLI). In this mini-review, we discuss these emerging clinical data for HMAs in the post-allo HPCT regimens and highlight the possible future role of azacitidine in this setting.
The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia.
From February 2003 ...to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E).
Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected median QOL-E standardized score 54, interquartile range 46-70; median EORTC global score 50, interquartile range 41-66. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients' perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores.
Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions.
<div data-canvas-width="568.0812">La investigación propuesta se centra en el contexto museístico de la ciudad de Turín (Italia), dentro de un acuerdo marco en curso entre el Politecnico di Torino y ...el Museo de Arte Oriental (MAO). Su objetivo es la construcción de un modelo para la gestión del flujo de trabajo que parte de la digitalización de las obras de arte y de los espacios y termina con la realización de modelos táctiles. El artículo comienza con una visión general sobre los métodos de conservación y difusión del patrimonio cultural y arquitectónico sobre la percepción y los gráficos táctiles. Presenta los primeros resultados del flujo de trabajo diseñado, centrándose especialmente en los experimentos de fabricación digital en el sistema abovedado del atrio del Palazzo Mazzonis (casa del MAO). La idea básica es que la exploración táctil de los artefactos ayuda a la participación del visitante, haciendo que la experiencia del museo sea más incisiva desde el punto de vista educativo y más inclusiva, en una perspectiva de “Diseño para todos”.
Il lavoro qui presentato ha previsto la realizzazione di modelli di carta de Le città invisibili di Italo Calvino Calvino 2009, utilizzando diverse tecniche di taglio e piegatura della carta per ...inventare scenografie, moduli, strutture e fondali. Nella presentazione del libro l’autore sottolinea come le città siano caratterizzate da una stratificazione di tanti elementi, caratteristica che ha portato alla realizzazione di modelli attraverso diversi livelli, che vanno a definire un “microcosmo”, una città in miniatura percepibile attraverso i sensi, che diventa oggetto «da pensare, da toccare, da guardare» Croset 1987, p. 48. Dal punto di vista tecnico i procedimenti adottati fanno riferimento alle ricerche sul paper folding, svolte da Joseph Albers The Public Paperfolding History Project 2023 presso il Bauhaus, a quelle del maestro giapponese Masahiro Chatani Chatani 1984 ed al paper artist britannico Paul Jackson Jackson 2014. Tagli, piegature, divisioni lineari e ripetizioni simmetriche consentono di passare dalla bidimensionalità propria della carta alla tridimensionalità del modello. La ricerca e la pratica ad essa connessa qui presentate sono confluite nel workshop di orientamento Paper City Tales del Politecnico di Torino, tenuto nel laboratorio modelli MODLab Arch, elaborato dagli autori e coordinato dal prof. Marco Vitali. Questa esperienza ha visto studenti del terzo e quarto anno di scuole secondarie di secondo grado piemontesi cimentarsi con la costruzione de Le città invisibili calviniane.
Abstract Background aims Filgrastim and lenograstim are the standard granulocyte colony-stimulating factor (G-CSF) agents for peripheral blood stem cell mobilization (PBSC) in patients who undergo ...autologous stem cell transplantation. Methods To assess whether biosimilars are effective, we conducted a single-center, prospective study that included 40 consecutive de novo multiple myeloma patients who received cyclophosphamide 4 g/m2 per day plus biosimilar filgrastim G-CSF to mobilize PBSC. These patients were compared with a group of 37 patients matched for age, diagnosis, previous chemotherapy and mobilization who had been treated with originator G-CSF. The mean number of CD34+ cells/μL in the peripheral blood was 199.6 ± 207.4 in the biosimilar and 192.8 ± 154.7 in the originator group ( P = 0.87). The median number of CD34+ cells/kg recipient collected was 11.5 ± 5.8 and 12.3 ± 5.3 in the biosimilar and originator groups, respectively ( P = 0.51). The mobilization failure rate was 2.5% and 2.7% in the biosimilar filgrastim and originator filgrastim cohorts ( P = NS), respectively. Results Twenty-nine patients in the biosimilar group and 28 patients in the originator group underwent autologous transplantation. There were no statistically significant differences between the biosimilar and originator G-CSF cohorts in terms of hematopoietic recovery parameters and transplant-related toxicities. Conclusions The efficacy of biosimilar G-CSF appears to be equivalent to the reference G-CSF.
Introduction: Management of Ph+ ALL has changed since the introduction of tyrosine kinase inhibitors (TKI). We previously reported the preliminary findings of the GIMEMA LAL 1509 total therapy ...protocol, based on dasatinib plus steroids administration as induction therapy (Chiaretti et al, ASH 2014). The updated results on overall survival (OS), disease-free survival (DFS) and the impact of a genetic-based prognostic stratification are hereby provided.
Methods: Steroids were administered from day -6 to day 31. Dasatinib (140 mg/day) was given between days 1 and 84. Patients reaching a complete molecular response (CMR, i.e. BCR/ABL1 to ABL1 ratio=0) at the end of induction (day 85) continued Dasatinib. Patients in complete hematologic remission (CHR), but not in CMR, underwent chemotherapy (clofarabine-cyclophosphamide) and/or an allogeneic transplant (HSCT), according to eligibility and donor availability. Dasatinib was administered until disease progression. Molecular testing was used to identify the presence of the BCR/ABL1 transcript on bone marrow samples, to define the fusion protein and to quantify BCR/ABL1 levels at baseline and follow-up (FU). Mutational screening was performed in relapsed cases, based on material availability. SNP array analysis was carried out using the Cytoscan HD arrays (Affymetrix, Santa Clara, CA) to identify genomic aberrations.
Results: 60/63 enrolled patients were eligible. Median age was 41.9 years (range 18.7-59.1), 34 were males and 26 females; median WBC count was 12.5 x 109/l (range 1.4-178.0); the p190 fusion product was detected in 33 patients, p210 in 18 and p190/p210 in 9. Median FU is 28.4 months (range 4.2-43.7). After the steroid pre-phase, 38 patients (63%) had a blast reduction ≥75%. At day 85, 58 patients were in CHR (97%), while 2, in CHR at day 57, lost it: both harbored the p210 fusion transcript. They both returned into CHR following chemotherapy. A sustained CMR was obtained in 11 patients (18.6%): 72% had a p190 fusion transcript. No deaths in induction occurred. Among the CMR patients, only 1 experienced a hematologic relapse, which carried a T315I mutation. Of the 46 non-CMR cases, 14 relapses occurred, 8 of which in p210+ patients. Overall, there have been 12 deaths in CHR. OS is 58.3% (95%CI: 44.4-76.3) at 36 months and DFS at 30 months is 48.9% (95%CI: 36.8.0-64.9). A better DFS was observed in patients who obtained a CMR compared to cases with minimal residual disease (MRD) at day 85 (75% vs 44%, p=0.06), and in p190+ vs p210+ patients (57.1% vs 39.6%, p=ns). Mutational screening, performed in 7/15 cases at hematologic relapse detected mutations in 5: 3 T315I and 2 V299L, of which 1 with a concomitant F317I and F317L. SNP array analysis, performed in 39 cases with available DNA, showed that the most frequent aberrations were deletions of IKZF1 (85%), PAX5 (38%), CDKN2A/B (33%), MLLT3 (33%), RB1 (28%) and JAK2 (28%). While IKZF1 deletions alone did not impact on CHR or CMRachievement and DFS, a significantly worse DFS (p=0.01) and increased cumulative incidence of relapse (CIR, p=0.024) were observed in cases harboring deletions of IKZF1 plus CDKN2A/B and PAX5 (DFS: 40% vs 65% at 18 months; CIR: 40% vs 14% at 18 months (Fig. 1A and B). The relevance of this finding was further refined by stratifying patients according to the fusion protein: the impact of IKZF1 plus CDKN2A/B and PAX5 deletions is prognostically relevant in p190+, but not in p210+ patients, possibly because of the worse outcome of the latter group (Fig. 2). Finally, this analysis identified a set of genes specifically deleted in CMR cases; investigations are ongoing on additional cases to validate their potential role in predicting response to TKI.
Conclusions: In this updated analysis of the GIMEMA 1509 trial, we confirm the effectiveness of a chemo-free induction in inducing CHR in almost all adult Ph+ ALL patients (97%) and CMR in a subgroup of cases (18.6%). OS and DFS at 36 months and 30 months, approaching 60% and 50%, are encouraging. More importantly, CMR achievement at day 85 is associated with extremely promising results, being 75% at 30 months, underlying that CMR should be regarded as a primary endpoint in Ph+ ALL. We confirm that p210+ patients may require an intensified approach, given the lower rate of CMR achievement and the higher relapse rate. Finally, we provide evidence that a broader genetic characterization at diagnosis allows a more refined prognostic stratification of Ph+ ALL patients.
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Martinelli:Pfizer: Consultancy; Ariad: Consultancy; AMGEN: Consultancy; BMS: Consultancy, Speakers Bureau; ROCHE: Consultancy; MSD: Consultancy; Novartis: Consultancy, Speakers Bureau. Foà:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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