COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. ...Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients. Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.
Waldenström macroglobulinemia (WM) is an uncommon lymphoma characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M (IgM). The ...disease may have an asymptomatic phase, or patients may present with symptoms and complications resulting from marrow or other tissue infiltration, or from physicochemical or immunological properties of the monoclonal IgM. Diagnosis of WM has been clearly defined, and genetic testing for somatic mutation of MYD88L265P is a useful tool for differential diagnosis from other conditions. Specific criteria that define symptomatic disease that needs treatment offer clinical guidance. The treatment of WM has evolved rapidly, with treatment options that include anti-CD20 monoclonal antibody-based combinations and BTK inhibitors. The choice of therapy is based on the need for rapid disease control, presence of specific disease complications, and patient's age. With the use of BTK inhibitors, the use of continuous therapy has been introduced as another option over fixed-duration chemoimmunotherapy. In this review, we focus on different clinical scenarios and discuss treatment options, based on the available data.
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Bone disease is a cardinal complication of multiple myeloma that affects quality of life and survival. Osteocytes have emerged as key players in the development of myeloma-related bone disease. Along ...with other factors, they participate in increased osteoclast activity, decreased osteoblast function, and immunosuppressed marrow microenvironment, which deregulate bone turnover and result in bone loss and skeletal-related events. Denosumab is a novel alternative to bisphosphonates against myeloma bone disease. Special considerations in this constantly evolving field are thoroughly discussed.
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Summary
Immunoglobulin light chain (AL) amyloidosis, the most common of the systemic amyloidosis, is characterized by the deposition of amyloid fibrils that derive from the aggregation of misfolded ...monoclonal immunoglobulin light chains. Amyloid fibrils disrupt tissue architecture and the pre‐fibril oligomers are directly toxic to myocardiac cells, causing cardiac dysfunction. The lethal consequences of AL amyloidosis are due to the toxic product and not due to the malignant behaviour of the plasma cell clone; however, the characteristics of this clone are associated with long‐term prognosis. Early and accurate diagnosis is the key to effective management, but is challenging. Modern chemotherapy options (including autologous transplantation, bortezomib, lenalidomide) have improved the outcomes of patients at low or intermediate risk, but the prognosis of patients with severe cardiac dysfunction is still poor. Therapies targeting amyloid deposits and the amyloidogenic process are under investigation and offer promise for better future treatments.
Although COVID-19 presents primarily as a lower respiratory tract infection transmitted via air droplets, increasing data suggest multiorgan involvement in patients that are infected. This systemic ...involvement is postulated to be mainly related to the SARS-CoV-2 virus binding on angiotensin-converting enzyme 2 (ACE2) receptors located on several different human cells. Lung involvement is the most common serious manifestation of the disease, ranging from asymptomatic disease or mild pneumonia, to severe disease associated with hypoxia, critical disease associated with shock, respiratory failure and multiorgan failure or death. Among patients with COVID-19, underlying cardiovascular comorbidities including hypertension, diabetes and especially cardiovascular disease, has been associated with adverse outcomes, whereas the emergence of cardiovascular complications, including myocardial injury, heart failure and arrhythmias, has been associated with poor survival. Gastrointestinal symptoms are also frequently encountered and may persist for several days. Haematological complications are frequent as well and have been associated with poor prognosis. Furthermore, recent studies have reported that over a third of infected patients develop a broad spectrum of neurological symptoms affecting the central nervous system, peripheral nervous system and skeletal muscles, including anosmia and ageusia. The skin, the kidneys, the liver, the endocrine organs and the eyes are also affected by the systemic COVID-19 disease. Herein, we provide a comprehensive overview of the organ-specific systemic manifestations of COVID-19.
Vaccination is a major tool for mitigating the coronavirus disease 2019 (COVID-19) pandemic, and mRNA vaccines are central to the ongoing vaccination campaign that is undoubtedly saving thousands of ...lives. However, adverse effects (AEs) following vaccination have been noted which may relate to a proinflammatory action of the lipid nanoparticles used or the delivered mRNA (i.e., the vaccine formulation), as well as to the unique nature, expression pattern, binding profile, and proinflammatory effects of the produced antigens – spike (S) protein and/or its subunits/peptide fragments – in human tissues or organs. Current knowledge on this topic originates mostly from cell-based assays or from model organisms; further research on the cellular/molecular basis of the mRNA vaccine-induced AEs will therefore promise safety, maintain trust, and direct health policies.
Coronavirus disease 2019 (COVID-19) mRNA vaccines induce robust immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet their cellular/molecular mode of action and the etiology of the induced adverse events (AEs) remain elusive.Lipid nanoparticles (LNPs) probably have a broad distribution in human tissues/organs; they may also (along with the packaged mRNA) exert a proinflammatory action.COVID-19 mRNA vaccines encode a transmembrane SARS-CoV-2 spike (S) protein; however, shedding of the antigen and/or related peptide fragments into the circulation may occur.Binding of circulating S protein to angiotensin-converting enzyme 2 (ACE2) (that is critical for the renin–angiotensin system balance) or to other targets, along with the possibility of molecular mimicry with human proteins, may contribute to the vaccination-related AEs.The benefit–risk profile remains in favor of COVID-19 vaccination, yet prospective pharmacovigilance and long-term monitoring of vaccinated recipients should be a public health priority.
Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the ...pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process. During the last years, osteocytes have emerged as key regulators of bone loss in myeloma through direct interactions with the myeloma cells. The myeloma-induced crosstalk among the molecular pathways establishes a positive feedback that sustains myeloma cell survival and continuous bone destruction, even when a plateau phase of the disease has been achieved. Targeted therapies, based on the better knowledge of the biology, constitute a promising approach in the management of myeloma-related bone disease and several novel agents are currently under investigation. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies.
How I treat relapsed multiple myeloma Kastritis, Efstathios; Terpos, Evangelos; Dimopoulos, Meletios A.
Blood,
05/2022, Letnik:
139, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Despite recent advances, multiple myeloma remains an incurable disease for most patients, and initial remission will be followed by relapses requiring therapy. For many, there will be several ...remissions and relapses until resistance develops to all available therapies. With the introduction of several new agents, myeloma treatment has changed drastically, and there are new options for the management of relapsed or refractory disease, including new drug classes with distinct mechanisms of action and cellular therapies. However, resistance to major drug classes used in first-line remains the most critical factor for the choice of treatment at relapse. Continuous lenalidomide-based therapy is used extensively at first-line, and resistance to lenalidomide has become the key factor for the choice of salvage therapy. Daratumumab is increasingly used in first-line, and soon patients that relapse while on daratumumab will become a common challenge. Three-drug regimens are the standard approach to manage relapsed disease. Adding drugs with new mechanisms of activity can improve outcomes and overcomes class resistance, but, until now, while biology is important, it can offer only limited guidance for the choice of therapy.
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Over the last few decades, significant improvement in outcomes has been observed for myeloma patients, mainly as a result of the use of currently available approved antimyeloma agents, along with ...combining autologous stem cell transplantation in the treatment of myeloma. With more targeted agents in development, the treatment of a myeloma patient at relapse has become complicated and, as a consequence, results in vast heterogeneity in treatment patterns. Although a consensus on the timing of initiation of treatment, the choice of agents to be used, and the role of transplant is less clear, we describe an evidence-based approach and the factors to consider upon relapse. We describe additional newer agents and targets that are under development, with the goal of achievement of durable remissions for myeloma patients.
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