ABSTRACT
The present research focuses on a continuum description of stratified metamaterials achieved through the superposition of layers with alternating chirality. Each layer is constructed as a periodic assembly of centre-symmetric periodic cells, formed by a recurring arrangement of rigid circular discs connected by elastic ligaments. The layers are interconnected through elastic pins passing through the centres of aligned discs, allowing for either restrained or free relative rotation. A micropolar continuum model is used to describe each individual layer. The overall response of the metamaterials to in-plane forces is derived using a multi-field non-local model, expressed in terms of the average and difference of displacement and rotational fields. The overall micropolar and standard (Cauchy) constitutive tensors have been determined in closed form. The validity of the equivalent generalized micropolar model has been confirmed through comparison with discrete Lagrangian solutions of representative examples. In addition, a detailed analysis of a pseudo-indentation test has been carried out. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'.
ABSTRACT
Background: Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload. Methods: We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected. Results: The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders. Conclusions: Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers.
ABSTRACT
This article focuses on characterizing a class of quasi-periodic metamaterials created through the repeated arrangement of an elementary cell in a fixed direction. The elementary cell consists of two building blocks made of elastic materials and arranged according to the generalized Fibonacci sequence, giving rise to a quasi-periodic finite microstructure, also called Fibonacci generation. By exploiting the transfer matrix method, the frequency band structure of selected periodic approximants associated with the Fibonacci superlattice, i.e. the layered quasi-periodic metamaterial, is determined. The self-similarity of the frequency band structure is analysed by means of the invariants of the symplectic transfer matrix as well as the transmission coefficients of the finite clusters of Fibonacci generations. A high-frequency continualization scheme is then proposed to identify integral-type or gradient-type non-local continua. The frequency band structures obtained from the continualization scheme are compared with those derived from the Floquet-Bloch theory to validate the proposed scheme. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1).'
ABSTRACT
BACKGROUND: Allogeneic hemopoietic stem cell transplantation (HSCT) currently remains the only curative treatment for patients with myelofibrosis (MF). Transplant related mortality (TRM) and relapse, remain two significant complications which need to be addressed. AIMS: The aim of this manuscript is to review current available reports on changes which have recently occurred, to improve the outcome of MF patients undergoing an allogeneic HSCT. METHODS: Published papers were used to analyze different aspects of allogeneic HSCT. RESULTS: Changes and updates are provided on selection of patients, prognostic systems, managing splenomegaly, conditioning regimens, predicting transplant outcome, stem cell sources, stem cell donors, graft versus host disease (GvHD) prophylaxis, patients with blast phase, hematopoietic reconstitution, disease markers, donor chimerism, and treatment of relapse. CONCLUSIONS: The review outlines new transplant platforms which are now available for patients with myelofibrosis, together with persisting problems, among which, older age combined with marrow fibrosis and an inflammatory disease. Relapse also requires aggressive monitoring of drivers mutations, and early cellular therapy.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Primary Myelofibrosis , Humans , Transplantation, Homologous/adverse effects , Graft vs Host Disease/etiology , Treatment Outcome , Neoplasm Recurrence, Local/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Chronic Disease , Recurrence , Risk Assessment , Transplantation Conditioning/adverse effectsABSTRACT
Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among others. Recently, the American Society for Transplantation and Cellular Therapy (ASTCT) published standardized definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism. To attempt broader international consensus, a panel of adult and pediatric physician transplant experts was assembled from European Society for Blood and Marrow Transplantation (EBMT), ASTCT, the Center for International Blood and Marrow Transplant Research (CIBMTR), and Asia-Pacific Blood and Marrow Transplantation (APBMT). Consensus was defined as ≥70% of voting members strongly agreeing or somewhat agreeing with a definition. With few exceptions, there was a consensus to endorse the prior ASTCT definitions. Importantly, we revised existing EBMT and CIBMTR data collection forms to align with these harmonized definitions that will facilitate research and international collaboration among transplant researchers and across transplant registries.
Subject(s)
Graft Rejection , Hematopoietic Stem Cell Transplantation , Humans , Hematopoietic Stem Cell Transplantation/methods , Allografts , Male , Female , Adult , Transplantation Chimera , Transplantation, Homologous/methodsSubject(s)
Cyclophosphamide , Cyclosporine , Graft vs Host Disease , Sirolimus , Humans , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Graft vs Host Disease/prevention & control , Male , Cyclosporine/therapeutic use , Female , Middle Aged , Sirolimus/therapeutic use , Sirolimus/administration & dosage , Adult , Hematopoietic Stem Cell Transplantation/methods , Aged , Adolescent , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Retrospective StudiesSubject(s)
Antibodies , Graft Rejection , Humans , Risk Factors , HLA Antigens , Graft Survival , Isoantibodies , Tissue DonorsABSTRACT
Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements.
Subject(s)
Acetates , Cystitis, Hemorrhagic , Cystitis , Cytomegalovirus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Quinazolines , Humans , Male , Cytomegalovirus , Cystitis/diagnosis , Cystitis/epidemiology , Cystitis/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Risk Factors , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/etiology , Alkylating Agents , Graft vs Host Disease/etiology , Retrospective StudiesABSTRACT
New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis. To inform patients' optimal care, we updated the 2015 guidelines on indications for and management of allogeneic haematopoietic stem-cell transplantation (HSCT) with the support of the European Society for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN). New recommendations were produced using a consensus-building methodology after a comprehensive review of articles released from January, 2015 to December, 2022. Seven domains and 18 key questions were selected through a series of questionnaires using a Delphi process. Key recommendations in this update include: patients with primary myelofibrosis and an intermediate-2 or high-risk Dynamic International Prognostic Scoring System score, or a high-risk Mutation-Enhanced International Prognostic Score Systems (MIPSS70 or MIPSS70-plus) score, or a low-risk or intermediate-risk Myelofibrosis Transplant Scoring System score should be considered candidates for allogeneic HSCT. All patients who are candidates for allogeneic HSCT with splenomegaly greater than 5 cm below the left costal margin or splenomegaly-related symptoms should receive a spleen-directed treatment, ideally with a JAK-inhibitor; HLA-matched sibling donors remain the preferred donor source to date. Reduced intensity conditioning and myeloablative conditioning are both valid options for patients with myelofibrosis. Regular post-transplantation driver mutation monitoring is recommended to detect and treat early relapse with donor lymphocyte infusion. In a disease where evidence-based guidance is scarce, these recommendations might help clinicians and patients in shared decision making.
Subject(s)
Hematopoietic Stem Cell Transplantation , Primary Myelofibrosis , Humans , Primary Myelofibrosis/therapy , Splenomegaly , Transplantation, Homologous , Hematopoietic Stem Cell Transplantation/methods , Spleen , Transplantation ConditioningSubject(s)
Leukemia, Erythroblastic, Acute , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Mutation , Leukemia, Erythroblastic, Acute/diagnosis , Leukemia, Erythroblastic, Acute/genetics , Leukemia, Erythroblastic, Acute/therapy , Fusion Proteins, bcr-abl/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.
Subject(s)
POEMS Syndrome , Peripheral Blood Stem Cell Transplantation , Humans , POEMS Syndrome/diagnosis , POEMS Syndrome/therapy , Transplantation, Autologous , Autografts , Cyclophosphamide/therapeutic useABSTRACT
Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/µL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×109/L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention.
Subject(s)
Hematopoietic Stem Cell Transplantation , Peripheral Blood Stem Cells , Humans , Hematopoietic Stem Cell Mobilization , Antigens, CD34 , Granulocyte Colony-Stimulating FactorABSTRACT
High dose Post transplant cyclophosphamide (PTCy) is now regarded as a very effective way of preventing acute and chronic GvHD, and it's use has rapidly expanded world-wide.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Cyclophosphamide/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
The current COVID-19 pandemic has placed unprecedented stress on the healthcare system, including HSCT. Several international organizations have created guidelines for managing different aspects of HSCT in the context of the pandemic. Comparing 2019 and 2020, our transplant center performed the same number of transplants. In both periods, transplants were mainly for patients with acute leukemia; thus, the urgency criteria was respected in light of pandemic restraints. Transplants by sibling donors and cord blood units remained the same, while transplants by unrelated donors were increased, in particular from European registries, and transplants by haploidentical donors were decreased. This change was made in light of the necessity of cryopreserving all apheresis products. We decided against cryopreserving bone marrow products due to the greater risk of drastic reduction in CD34 + cell count during the process. For urgent cases with only a haploidentical donor available, we opted for the use of PBSC following stimulation with G-CSF. GvHD prophylaxis was performed with PTCY on days + 3 + 5, cyclosporine with tapering from day + 100, and mycophenolic acid until day + 90 post-HSCT. Post-transplant outcomes such as graft failure, sepsis, and GVHD were not affected by the changes implemented. As a result of logistic difficulties, we halted our Car-T program from the start of the lockdown in March 2020 until September 2020. In accord with international guidelines, we were able to continue our HSCT program in the order to ensure a lifesaving treatment for patients with hematologic diseases for whom this procedure cannot be postponed.
Subject(s)
COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Pandemics , Communicable Disease Control , Hematopoietic Stem Cell Transplantation/methods , Unrelated Donors , Graft vs Host Disease/prevention & control , Transplantation Conditioning/methodsABSTRACT
PURPOSE: Depressive disorders are the most common manifestation of psychological distress in allogenic hematopoietic stem cell transplantation. Few studies have yet investigated the relationship between therapeutic educational interventions and outcomes in these patients with specific attention to those related to mental health. Aim of this study was to understand how much educational intervention can represent a protective factor in preventing psycho-emotional distress-related issues in this setting. DESIGN: A prospective observational study of a multicenter cohort was conducted. PARTICIPANTS: Adult patients undergoing allogeneic hematopoietic stem cell transplantation. METHODS: A pre-transplant therapeutic educational programme was offered to a cohort of adult patients undergoing allo-HSCT recruited in ten transplant centers of the GITMO network between May 2018 and January 2019. Depression, Anxiety and Stress scale was used to collect data on psycho-emotional distress at admission (T0), at the day of transplant (T1) and at discharge (T2). Descriptive data were collected and reported, and comparative analyses were done among patients who were compliant with the pre-transplant educational intervention and those who did not (for any reason). FINDINGS: A cohort of 133 allo-HSCT patients was observed. In patients who did not receive pre-transplant educational intervention, higher levels of depression at admission (p = 0.01) and at the day of transplant (p = 0.03), higher levels of anxiety (p = 0.01 and p = 0.01 respectively) as well as higher levels of stress (p < 0.01 and p = 0.01) were observed. Problem solving and "face to face" interview were the best methods to provide education to patients. Those who received pre-transplant education through "face-to-face" interview reported significant low levels of depression during the whole hospital stay period (p < 0.01; p = 0.01; p = 0.01) and less anxiety and stress at admission (p < 0.05 and p = 0.01 respectively). Depression was more represented in female than male participants at T0 (16.5% vs 9.0%; p = 0.01), while among T0 and T2 the males had a significant higher increasing of depression than females (p = 0.03). CONCLUSION: Our study demonstrated that pretreatment therapeutic educational programs with specific learning modalities can be effective in limiting the potential risk of developing moderate-to-severe anxiety-depressive states and stress symptoms related to allo-HSCT. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Further studies are needed to confirm our results and to understand whether containing psycho-emotional distress can have any relationship with medium- and long-term post-transplant complications.