Splenectomy, while often necessary in otherwise healthy patients after major trauma, finds its primary indication for patients with underlying malignant or nonmalignant hematologic diseases. ...Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infections found in splenectomized patients are due to Gram-negative (G-) bacteria. The underlying disease is the most important factor in determining the frequency and severity of infections. So, splenectomy for malignant diseases has the major risk of infections.
The power transmission lines are the link between power plants and the points of consumption, through substations. Most importantly, the assessment of damaged aerial power lines and rusted conductors ...is of extreme importance for public safety; hence, power lines and associated components must be periodically inspected to ensure a continuous supply and to identify any fault and defect. To achieve these objectives, recently, Unmanned Aerial Vehicles (UAVs) have been widely used; in fact, they provide a safe way to bring sensors close to the power transmission lines and their associated components without halting the equipment during the inspection, and reducing operational cost and risk. In this work, a drone, equipped with multi-modal sensors, captures images in the visible and infrared domain and transmits them to the ground station. We used state-of-the-art computer vision methods to highlight expected faults (i.e., hot spots) or damaged components of the electrical infrastructure (i.e., damaged insulators). Infrared imaging, which is invariant to large scale and illumination changes in the real operating environment, supported the identification of faults in power transmission lines; while a neural network is adapted and trained to detect and classify insulators from an optical video stream. We demonstrate our approach on data captured by a drone in Parma, Italy.
The objective of this study was to evaluate the clinical features, prognostic factors, and efficacy of treatments in patients with blastic plasmacytoid dendritic cell neoplasm with a leukemic ...presentation at onset of the disease. In order to do this, a retrospective multicenter study was performed from 2005-2011 in 28 Italian hematology divisions in which 43 cases were collected. Forty-one patients received an induction therapy, consisting of an acute myeloid leukemia-type regimen in 26 patients (60%) and acute lymphoid leukemia/lymphoma-type regimen in 15 patients (35%). Six patients (14%) underwent allogeneic hematopoietic stem cell transplantation. Seventeen patients (41%) achieved a complete remission: seven after acute myeloid leukemia-type treatment and 10 after an acute lymphoid leukemia/lymphoma-type regimen, with a significant advantage for acute lymphoid leukemia/lymphoma-type chemotherapy (P=0.02). Relapse occurred in six of the 17 patients (35%) who achieved complete remission, more frequently after acute lymphoid leukemia/lymphoma-type chemotherapy. The median overall survival was 8.7 months (range, 0.2-32.9). The patients treated with an acute myeloid leukemia-type regimen had an overall survival of 7.1 months (range, 0.2-19.5), whereas that of the patients receiving acute lymphoid leukemia/lymphoma-type chemotherapy was 12.3 months (range, 1-32.9) (P=0.02). The median overall survival of the allogeneic hematopoietic stem cell transplant recipients was 22.7 months (range, 12-32.9), and these patients had a significant survival advantage compared to the non-transplanted patients (median 7.1 months, 0.2-21.3; P=0.03). In conclusion, blastic plasmacytoid dendritic cell neoplasm with bone-marrow involvement is an aggressive subtype of high-risk acute leukemia. The rarity of this disease does not enable prospective clinical trials to identify the better therapeutic strategy, which, at present, is based on clinicians' experience.
The aim of our review has been to give an appropriate idea of analogies and differences between primitive MDS (p-MDS) and t-MDS throughout an accurate reviewing of English peer-reviewed literature ...focusing on clinical, cytogenetic, epigenetic, and somatic mutation features of these two groups of diseases. Therapy-related MDS (t-MDS) are classified by WHO together with therapy-related acute myeloid leukemia (t-AML) in the same group, named therapy-related myeloid neoplasm. However, in clinical practice, the diagnosis of t-MDS is made with the same criteria as for primitive MDS (p-MDS), and the only difference is a previous non-myeloid neoplasm. The prognosis and the consequent therapy can be established following the same criteria as for p-MDS, and the therapy is generally decided using the same criteria. We stress the possible difference in cytogenetics, mutations, and epigenetics to distinguish the two forms. Actually, there is no marker specific for t-MDS either in cytogenetics, epigenetics, or mutations; however, some alterations are also frequent in t-MDS and, in general, they induce a poorer prognosis. So, the high-risk forms in t-MDS are prevalent. The present literature data suggest classifying the t-MDS as a subgroup of MDS and introducing some parameters to evaluate the probability of previous therapy in inducing MDS. An important issue remains the patient's fitness, which strongly influences the outcome.
Sustained engagement of the B-cell receptor (BCR) increases apoptosis resistance in chronic lymphocytic leukemia (CLL) B cells, whereas transient stimulation usually has an opposite effect. The ...antiapoptotic BCR signal has been associated with prolonged activation of the PI3K/Akt and MEK/ERK pathways, which are key regulators of survival and proliferation in various cell types. To further define the relative contribution of the Akt and ERK kinases in regulating CLL B-cell survival, we introduced constitutively active mutants of Akt and MEK in primary CLL B cells and evaluated changes in the expression of relevant pro- and antiapoptotic proteins. Sustained activation of Akt resulted in increased leukemic cell viability and increased expression of the antiapoptotic proteins Mcl-1, Bcl-xL, and X-linked inhibitor of apoptosis protein (XIAP), thus largely recapitulating the effects of sustained BCR stimulation. Constitutively active MEK2 also up-regulated XIAP, but did not show a significant impact on leukemic cell survival. Down-regulation of Mcl-1 by siRNA treatment induced rapid and potent apoptosis in CLL B cells and blocked the antiapoptotic effect of sustained BCR stimulation, whereas down-regulation of Bcl-xL and XIAP did not affect leukemic cell viability. These data demonstrate that Akt and Mcl-1 are major components of a survival pathway that can be activated in CLL B cells by antigen stimulation.
Herein, we report the homo- and co-polymerization of ethylene (E) with norbornene (NB) catalyzed by vanadium(III) phosphine complexes of the type VCl
(PMe
Ph
)
n = 2 (
), 1 (
) and VCl
(PR
)
R = ...phenyl (Ph,
), cyclohexyl (Cy,
),
-butyl (
Bu,
). In the presence of Et
AlCl and Cl
CCOOEt (ETA),
-
exhibit good activities for the polymerization of ethylene, affording linear, semicrystalline PEs with a melting temperature of approximately 130 °C. Mainly alternating copolymers with high comonomer incorporation were obtained in the E/NB copolymerization. A relationship was found between the electronic and steric properties of the phosphine ligands and the catalytic performance. Overall, the presence of electron-withdrawing ligand substituents increases the productivity, complexes with aryl phosphine (weaker σ-donor character) exhibiting a higher (co)polymerization initiation rate than those with alkyl phosphines (stronger σ-donor character). Steric effects also seem to play a key role since
and
, having large size phosphines (PCy
θ = 170° and P
Bu
θ = 182°, respectively) are more active than
(PMe
Ph θ = 122°). In this case, the larger size of P
Bu
and PCy
likely compensates for their higher donor strength compared to PMe
Ph.
Treatment of refractory and relapsed (R/R) B acute lymphoblastic leukemia (B-ALL) is an unmet medical need in both children and adults. Studies carried out in the last two decades have shown that ...autologous T cells engineered to express a chimeric antigen receptor (CAR-T) represent an effective technique for treating these patients. Antigens expressed on B-cells, such as CD19, CD20, and CD22, represent targets suitable for treating patients with R/R B-ALL. CD19 CAR-T cells induce a high rate (80-90%) of complete remissions in both pediatric and adult R/R B-ALL patients. However, despite this impressive rate of responses, about half of responding patients relapse within 1-2 years after CAR-T cell therapy. Allo-HSCT after CAR-T cell therapy might consolidate the therapeutic efficacy of CAR-T and increase long-term outcomes; however, not all the studies that have adopted allo-HSCT as a consolidative treatment strategy have shown a benefit deriving from transplantation. For B-ALL patients who relapse early after allo-HSCT or those with insufficient T-cell numbers for an autologous approach, using T cells from the original stem cell donor offers the opportunity for the successful generation of CAR-T cells and for an effective therapeutic approach. Finally, recent studies have introduced allogeneic CAR-T cells generated from healthy donors or unmatched, which are opportunely manipulated with gene editing to reduce the risk of immunological incompatibility, with promising therapeutic effects.
Infections remain a significant problem in myelodysplastic syndromes (MDS) in treated as well in non-treated patients and assume a particular complexity. The susceptibility to infections is due, in ...the absence of intensive chemotherapies, mainly to functional defects in the myeloid lineage with or without neutropenia. Furthermore, MDS includes a heterogeneous group of patients with very different prognosis, therapy and risk factors regarding survival and infections. You should distinguish risk factors related to the disease, like as neutrophils function impairment, neutropenia, unfavorable cytogenetics and bone marrow insufficiency; factors related to the patient, like as age and comorbidities, and factors related to the therapy. When the patients with MDS are submitted to intensive chemotherapy with and without hematopoietic stem cell transplantation (HSCT), they have a risk factor for infection very similar to that of patients with acute myeloid leukemia (AML), and mostly related to neutropenia. Patients with MDS treated with supportive therapy only or with demethylating agent or lenalidomide or immunosuppressive drugs should have a tailored approach. Most of the infections in MDS originate from bacteria, and the main risk factors are represented by neutropenia, thrombocytopenia, and unfavorable cytogenetics. Thus, it is reasonable to give antibacterial prophylaxis to patients who start the therapy with demethylating agents with a number of neutrophils <500 × 10
/L, or with thrombocytopenia and unfavorable cytogenetics. The antifungal prophylaxis is not considered cost/benefit adequate and should be taken into consideration only when there is an antecedent fungal infection or presence of filamentous fungi in the surveillance cultures. Subjects submitted to immunosuppression with ATG+CSA have a high rate of infections, and when severely neutropenic should ideally be nursed in isolation, should be given prophylactic antibiotics and antifungals, regular mouth care including an antiseptic mouthwash.
CAR-T Cell Therapy for T-Cell Malignancies Testa, Ugo; Chiusolo, Patrizia; Pelosi, Elvira ...
Mediterranean journal of hematology and infectious diseases,
01/2024, Letnik:
16, Številka:
1
Journal Article
Odprti dostop
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell lymphoid neoplasia and, in some instances, improved disease outcomes. Thus, six FDA-approved commercial ...CAR-T cell products that target antigens preferentially expressed on malignant B-cells or plasma cells have been introduced in the therapy of B-cell lymphomas, B-ALLs, and multiple myeloma. These therapeutic successes have triggered the application of CAR-T cell therapy to other hematologic tumors, including T-cell malignancies. However, the success of CAR-T cell therapies in T-cell neoplasms was considerably more limited due to the existence of some limiting factors, such as: 1) the sharing of mutual antigens between normal T-cells and CAR-T cells and malignant cells, determining fratricide events and severe T-cell aplasia; 2) the contamination of CAR-T cells used for CAR transduction with malignant T-cells. Allogeneic CAR-T products can avoid tumor contamination but raise other problems related to immunological incompatibility. In spite of these limitations, there has been significant progress in CD7- and CD5-targeted CAR-T cell therapy of T-cell malignancies in the last few years.
PDF
