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Rationale and design of the German-speaking myeloma multicenter group (GMMG) trial HD6: a randomized phase III trial on the effect of elotuzumab in VRD induction/consolidation and lenalidomide maintenance in patients with newly diagnosed myeloma.

BACKGROUND: Despite major advances in therapy, multiple myeloma is still an incurable malignancy in the majority of patients. To increase survival, deeper remissions (i.e. CR) translating into longer PFS need to be achieved. Incorporation of new drugs (i.e. bortezomib and lenalidomide) as induction and maintenance treatment in an intensified treatment concept, including high dose melphalan (200 mg/m2), has resulted in increased CR rates, and is considered the standard of care for younger patients. Elotuzumab in combination with lenalidomide and dexamethasone has given better results as lenalid

Kidney Disease and Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with hematologic malignancies and certain solid tumors and nonmalignant hematologic conditions. Both AKI and CKD occur commonly after HSCT and are associated with significant morbidity and mortality. AKI and CKD in this setting may result from direct effects of the transplant or be caused by pretransplant bone marrow conditioning regimens and/or nephrotoxic agents administered in the post-transplant period. In this article, we review the epidemiology, risk factors, etiologies, pathophysiology, diagnos

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… Higher than expected platelet transfusion needs 3. … Refractoriness to platelet transfusions 4. 50% reduction or greater in baseline platelet count after full platelet engraftment Elevated LDH | >ULN for age Schistocytes | Present Hypertension | >99th percentile for age (<18 yr), or systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg (≥18 yr) Elevated sC5b …

Erythropoiesis: insights into pathophysiology and treatments in 2017.

Erythropoiesis is a tightly-regulated and complex process originating in the bone marrow from a multipotent stem cell and terminating in a mature, enucleated erythrocyte.Altered red cell production can result from the direct impairment of medullary erythropoiesis, as seen in the thalassemia syndromes, inherited bone marrow failure as well as in the anemia of chronic disease. Alternatively, in disorders such as sickle cell disease (SCD) as well as enzymopathies and membrane defects, medullary erythropoiesis is not, or only minimally, directly impaired. Despite these differences in pathophysiolo

P1691: PALLIATIVE CARE IN HEMATOLOGICAL PATIENTS IS RELATED TO LESS AGGRESSIVE TREATMENT IN THE END-OF-LIFE, A RETROSPECTIVE STUDY.

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MUKtwelve protocol: a phase II randomised, controlled, open, parallel group, multicentre trial of selinexor, cyclophosphamide and prednisolone (SCP) versus cyclophosphamide and prednisolone (CP) in patients with relapsed or refractory multiple myeloma.

IntroductionMultiple myeloma is a malignancy of plasma cells with around 6000 new cases per year in the UK. Cyclophosphamide plus prednisolone is considered a standard of care for disease and symptom control in the advanced relapsed or refractory myeloma setting within the UK NHS. The selective nuclear export inhibitor, selinexor, has been relatively well tolerated in previous clinical trials and offers promise when used in combination with a wide range of other anti-cancer treatments. Here, we investigate if the addition of selinexor can improve responses to cyclophosphamide plus prednisolone

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… Platelet support is permitted within 14 days prior to randomisation, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility Absolute neutrophil count ≥1.0 x 10 9 /L. … Platelet support is permitted within 14 days prior to starting SCP, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility Absolute neutrophil count ≥1.0 x 10 9 /L. Haemoglobin ≥80 g/L. …

Development and validation of predictive models of early immune effector cell-associated hematotoxicity.

AbstractImmune effector cell-associated hematotoxicity (ICAHT) is associated with morbidity and mortality after chimeric antigen receptor (CAR) T-cell therapy. To date, the factors associated with ICAHT are poorly characterized, and there is no validated predictive model of ICAHT as defined by current consensus criteria. Therefore, we performed comprehensive univariate analyses to identify factors associated with severe (grade 3-4) early ICAHT (eICAHT) in 691 patients who received commercial or investigational CAR T-cell therapy for hematologic malignancies. In univariate logistic regression,

Lower-Risk Myelodysplastic Syndrome (MDS) Patients Exhibit Diminished Proteasome Proteolytic Activity and High Intracellular Reactive Oxygen Species (ROS) Levels.

Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and an elevated risk of transformation to acute myeloid leukemia (AML). Available disease-modifying treatment approaches are limited. The ineffectiveness of proteasome inhibitors (PIs) in MDS patients is currently investigated, although it is unclear whether they rapidly develop resistance to PIs or whether proteasome proteolytic activity (PPA) is constitutively lower in the hematopoietic cells of these patients, thus limiting treatment effecti

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… Increased oxidative stress in acute myeloid leukemia patients after red blood cell transfusion, but not platelet transfusion, results mainly from the oxidative/nitrative protein damage: an exploratory study. Czubak-Prowizor K, Trelinski J, Stelmach P, Stelmach P, Madon A, Zbikowska HM. …

The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Poster Session (P001-P706).

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Pulmonary and Hepatic Complications of Hematopoietic Cell Transplantation

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Adverse Reaction to COVID-19 mRNA Vaccination in a Patient With VEXAS Syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a rare genetic disorder originating from a somatic mutation in the hematopoietic stem cells. This syndrome was first described in 2020 and carries many clinical features that other conditions cannot explain. Widespread autoinflammation is the primary process the disease presents, with high morbidity and mortality in those who show signs of bone marrow failure. Treatment is complex, and response to current therapies is poor. Long-term prognosis carries a mortality of 50%. In addition, the advancement of new-generation

Utility of bronchoalveolar lavage in diagnosing respiratory tract infections in patients with hematological malignancies: are invasive diagnostics still needed?

BackgroundPatients treated for hematological malignancies have an increased risk of serious infections. Diagnosis and prompt initiation of therapy are essential. Bronchoalveolar lavage (BAL) is a well-established investigation for identifying the cause of pulmonary infiltrates in immunocompromised patients. The aim of the study was to determine the diagnostic yield of BAL in patients treated for hematological malignancies and how often it contributed to a modification of the anti-infectious therapy.MethodsWe reviewed records from 151 consecutive BAL procedures in 133 adult patients with hemato

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… Prophylactic platelet transfusions were given prior to BAL in cases of severe thrombocytopenia. BAL was performed according to a standardized procedure by a limited number of experienced specialists in the day-care unit of the Department of Pulmonary Medicine, Uppsala University Hospital. … The practice of giving prophylactic platelet transfusions prior to BAL in severely thrombocytopenic patients has never been proven to be necessary, but continues to seem reasonable. Our study has some limitations. …

At-Home Care Program for Acute Myeloid Leukemia Induction Phase in Patients Treated with Venetoclax-Based Low-Intensity Regimens.

Background: Even though venetoclax in combination with azacitidine (VenAza) is considered a low-intensity regimen, its patients present a high incidence of cytopenia and infections during the first courses, making the initial management a challenging phase. Methods: This difficulty in our center led to the establishment of an At-Home (AH) program for ramp-up and follow-up patients during the VenAza combination induction phase focused on therapy administration, patient and caregiver education, and management of adverse events (AEs). A total of 70 patients with newly diagnosed acute myeloid leuk

Early Administration of Convalescent Plasma Improves Survival in Patients with Hematological Malignancies and COVID-19.

The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48-72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the h

Impact of Skeletal Muscle Depletion on Patients with Myelodysplastic Syndrome Treated with Azacitidine.

BackgroundAzacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated.MethodsThis retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height.ResultsOf the enrolled patients, 3

Резюме МКАРЕ 2023 77th Национальный конгресс &quot; СИААРТИ &quot;

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4th ISTM Annual Conference, TRANSMEDCON 2015, Kolkata

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Tolerability of obinutuzumab therapy in patients with rituximab-relapsed/refractory B-cell malignancies - a retrospective single center cohort study.

Background & aimIn randomised clinical trials, the type II anti-CD20 antibody obinutuzumab has been shown to be more effective than rituximab for therapy of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). However, this enhanced efficacy was linked with elevated rates of high-grade adverse events. The aim of this study was to assess the tolerability and toxicity profile of obinutuzumab treatment in routine patients with CLL and FL, of whom the majority had experienced toxicity or resistance to rituximab.MethodsThis retrospective cohort study investigated fifteen obinutuzumab-tr

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compar

Unmet Needs and Challenges in Cancer-Associated Venous Thromboembolism.

Cancer-associated venous thromboembolism (CA-VTE) is a significant complication in oncology, contributing to morbidity, mortality, and increased healthcare utilization. Due to multiple patient- and disease-related factors, patients with cancer are at a markedly elevated risk for VTE, particularly within the first 6 months of diagnosis. The aim of this review is to provide an overview of current challenges and unmet needs in CA-VTE prediction, prevention and management. While the Khorana score remains the most widely used risk stratification tool, its limited sensitivity has prompted the develo

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… For severe thrombocytopenia with platelet count < 25,000 and an acute CA-VTE event, platelet transfusion should be considered in order to provide safe anticoagulation [ 96 ]. Frequent platelet transfusion is not always clinically feasible. 10.2. … The objective of this study is to evaluate the superiority of a modified dose LMWH strategy in reducing clinically relevant bleeding events compared to full-dose LMWH with platelet transfusion. The study is currently active and recruiting patients. …

COVID-19 vaccination prevents a more severe course and treatment with complement inhibitors reduce worsening hemolysis during the Omicron pandemic in patients with PNH: a single-center study.

ObjectiveParoxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease characterized by chronic complement-mediated hemolysis. The concentrated outbreak of coronavirus disease 2019 (COVID-19) in China after 6 December 2022, provided an opportunity to observe the disease course of PNH during an active Omicron infection epidemic.Patients and methodPatients diagnosed with PNH at Peking Union Medical College Hospital (PUMCH) before 6 December 2022, were followed up until 10 April 2023. Clinical data related to coronavirus infection and hemolysis were recorded. Factors influencing the infect