An example of active circulation control of the unsteady separated flow past a semi-infinite plate

Active circulation control of the two-dimensional unsteady separated flow past a semiinfinite plate with transverse motion is considered. The rolling-up of the separated shear layer is modelled by a point vortex whose time-dependent circulation is predicted by an unsteady Kutta condition. A suitable vortex shedding mechanism introduced. A control strategy able to maintain constant circulation when a vortex is present is derived. An exact solution for the nonlinear controller is then obtained. Dynamical systems analysis is used to explore the performance of the controlled system. The control strategy is applied to a class of flows and the results are discussed. A procedure to determine the position and the circulation of the vortex, knowing the velocity signature on the plate, is derived. Finally, a physical explanation of the control mechanism is presented

Catheter-related thrombosis in hematologic patients

For many years central venous catheters (CVC) have been utilized to monitor hemodynamics and to deliver parenteral nutrition, blood products, pharmacological therapies or infusion fluids. Recently, CVC use has greatly increased with significant impact on the administration of chemotherapy, stem cell transplantation and other treatments to cancer patients. However, CVC use may be accompanied by a variety of side-effects, which increase with the duration of implantation. The most common catheter-related complications are thrombotic events and blood-stream infections. The true incidence of these complications is still uncertain and has changed over time due to CVC device improvement. More data are available in solid tumor than in oncohematologic patients. Recently, much attention has been paid to the issues of prevention and treatment of these complications. Some strategies have been proposed: fixed dose warfarin or low molecular weight heparins have been evaluated in some clinical trials of thromboprophylaxis in this condition. However, more studies are still needed to address this issue. This review will focus on CVC use and complications in oncohematologic patients

Biosensors in clinical practice : focus on oncohematology

Biosensors are devices that are capable of detecting specific biological analytes and converting their presence or concentration into some electrical, thermal, optical or other signal that can be easily analysed. The first biosensor was designed by Clark and Lyons in 1962 as a means of measuring glucose. Since then, much progress has been made and the applications of biosensors are today potentially boundless. This review is limited to their clinical applications, particularly in the field of oncohematology. Biosensors have recently been developed in order to improve the diagnosis and treatment of patients affected by hematological malignancies, such as the biosensor for assessing the in vitro pre-treatment efficacy of cytarabine in acute myeloid leukemia, and the fluorescence resonance energy transfer-based biosensor for assessing the efficacy of imatinib in chronic myeloid leukemia. The review also considers the challenges and future perspectives of biosensors in clinical practice

Mesenchymal Stem Cells in Myeloid Malignancies: A Focus on Immune Escaping and Therapeutic Implications

The importance of the bone marrow microenvironment forming the so-called niche in physiologic hemopoiesis is largely known, and recent evidences support the presence of stromal alterations from the molecular to the cytoarchitectural level in hematologic malignancies. Various alterations in cell adhesion, metabolism, cytokine signaling, autophagy, and methylation patterns of tumor-derived mesenchymal stem cells have been demonstrated, contributing to the genesis of a leukemic permissive niche. This niche allows both the ineffective haematopoiesis typical of myelodysplastic syndromes and the differentiation arrest, proliferation advantage, and clone selection which is the hallmark of acute myeloid leukemia. Furthermore, the immune system, both adaptive and innate, encompassing mesenchymal-derived cells, has been shown to take part to the leukemic niche. Here, we critically review the state of art about mesenchymal stem cell role in myelodysplastic syndromes and acute myeloid leukemia, focusing on immune escaping mechanisms as a target for available and future anticancer therapies

Lenalidomide in the treatment of chronic lymphocytic leukemia

The application of nucleoside analogue-based chemotherapy and immunotherapy with rituximab or alemtuzumab has increased both response rate and survival in patients with Chronic Lymphocytic Leukemia (CLL). However, because none of these therapies is curative, sequential therapeutic regimens are required. The majority of patients with relapsed or refractory CLL carry poor prognostic factors and show shorter overall survival and resistance to standard treatment. Numerous drugs have recently been approved for CLL therapy and many novel agents are under clinical investigation. The role of the tumor microenvironment and of immune dysfunction in CLL have allowed to enlarge the therapeutic armamentarium for CLL patients. This article will provide a comprehensive summary regarding mechanism of action, efficacy and safety of lenalidomide in CLL patients. Relevant clinical trials using lenalidomide alone or in combinations are discussed. Lenalidomide shows good activity also in relapsed/refractory or treatment-naive CLL patients. Definitive data from ongoing studies are needed to validate overall and progression-free survival. The toxicity profile might limit lenalidomide use because it can result in serious side effects, but largely controlled by gradual dose escalation. Further understanding of the exact mechanism of action in CLL will allow more efficacious use of lenalidomide alone or in combination regimen

Reduced intensity conditioning allogeneic transplant for advanced chronic lymphocytic leukemia

We report the preliminary results of 12 patients with advanced stage chronic lymphocytic leukemia (CLL) transplanted following reduced intensity conditioning (RIC. With a median of 22 months of follow-up, 9 patients are alive and 3 have died of progressive disease, graft-versus-host disease (GVHD) or toxic hepatitis. Acute grade I-III GVHD occurred in 33% of patients and chronic GVHD in 50%. Eight of the 12 patients achieved a complete remission (CR) and 2 patients a partial remission (PR). Donor lymphocyte infusion was effective in 6 patients. Event-free survival, progression-free survival and non-relapse mortality at 3 years were 68%, 42% and 16%, respectively. Our results show successful immunomodulation and reduction in tumor burden in high risk CL

Autoimmune cytopenias in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia and autoimmune granulocytopenia. The distinction of immune cytopenias from cytopenias due to bone marrow infiltration, usually associated with a worse outcome and often requiring a different treatment, is mandatory. AIHA and ITP are more frequently found in patients with unfavorable biological risk factors for CLL. AIC secondary to CLL respond less favorably to standard treatments than their primary forms, and treating the underlying CLL with chemotherapy or monoclonal antibodies may ultimately be necessary

Increased risk of venous thromboembolism in patients with acute leukaemia

Patients with malignancies have an increased risk for venous thromboembolisms (VTE), but data on patients with acute leukaemia are very limited so far. We found VTE in 12% of 455 patients with acute leukaemia, half of which occurred in association with central venous catheters, with equal risk of ALL and AML