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Annals of Oncology : Official Journal... Mar 2022Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell...
Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA).
BACKGROUND
Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future.
DESIGN
The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field.
RESULTS
Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues.
CONCLUSIONS
We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.
Topics: Accreditation; Adult; Bone Marrow; Hematology; Humans; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen
PubMed: 34923107
DOI: 10.1016/j.annonc.2021.12.003 -
American Journal of Hematology Jul 2019D-dimer is an indirect marker of fibrinolysis and fibrin turnover; this molecule exhibits unique properties as a biological marker of hemostatic abnormalities as well as... (Review)
Review
D-dimer is an indirect marker of fibrinolysis and fibrin turnover; this molecule exhibits unique properties as a biological marker of hemostatic abnormalities as well as an indicator of intravascular thrombosis. D-dimer is a soluble fibrin degradation product that results from the systematic degradation of vascular thrombi through the fibrinolytic mechanism. Because of this, the D-dimer serves as a valuable marker of activation of coagulation and fibrinolysis in a number of clinical scenarios. Most commonly, D-dimer has been extensively investigated for excluding the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D-dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and for monitoring other conditions in which the patient is at high risk of bleeding or thrombosis. Limitations of the assay include D-dimer elevation in a constellation of clinical scenarios (age, pregnancy, and cancer) and lack of clinical standardization.
Topics: Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Male; Pregnancy; Pregnancy Complications, Hematologic; Thrombosis; Venous Thromboembolism
PubMed: 30945756
DOI: 10.1002/ajh.25482 -
Critical Care (London, England) Feb 2020Spontaneous intracerebral hemorrhage is a devastating disease, accounting for 10 to 15% of all types of stroke; however, it is associated with disproportionally higher... (Review)
Review
Spontaneous intracerebral hemorrhage is a devastating disease, accounting for 10 to 15% of all types of stroke; however, it is associated with disproportionally higher rates of mortality and disability. Despite significant progress in the acute management of these patients, the ideal surgical management is still to be determined. Surgical hematoma drainage has many theoretical benefits, such as the prevention of mass effect and cerebral herniation, reduction in intracranial pressure, and the decrease of excitotoxicity and neurotoxicity of blood products.Several surgical techniques have been considered, such as open craniotomy, decompressive craniectomy, neuroendoscopy, and minimally invasive catheter evacuation followed by thrombolysis. Open craniotomy is the most studied approach in this clinical scenario, the first randomized controlled trial dating from the early 1960s. Since then, a large number of studies have been published, which included two large, well-designed, well-powered, multicenter, multinational, randomized clinical trials. These studies, The International Surgical Trial in Intracerebral Hemorrhage (STICH), and the STICH II have shown no clinical benefit for early surgical evacuation of intraparenchymal hematoma in patients with spontaneous supratentorial hemorrhage when compared with best medical management plus delayed surgery if necessary. However, the results of STICH trials may not be generalizable, because of the high rates of patients' crossover from medical management to the surgical group. Without these high crossover percentages, the rates of unfavorable outcome and death with conservative management would have been higher. Additionally, comatose patients and patients at risk of cerebral herniation were not included. In these cases, surgery may be lifesaving, which prevented those patients of being enrolled in such trials. This article reviews the clinical evidence of surgical hematoma evacuation, and its role to decrease mortality and improve long-term functional outcome after spontaneous intracerebral hemorrhage.
Topics: Cerebral Hemorrhage; Craniotomy; Hematoma; Humans; Treatment Outcome
PubMed: 32033578
DOI: 10.1186/s13054-020-2749-2 -
Journal of Hematology & Oncology Jan 2023Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple... (Review)
Review
Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple humoral and cellular immune abnormalities result in accelerated platelet destruction and suppressed platelet production in ITP. The diagnosis remains a clinical exclusion of other causes of thrombocytopenia. Treatment is not required except for patients with active bleeding, severe thrombocytopenia, or cases in need of invasive procedures. Corticosteroids, intravenous immunoglobulin, and anti-RhD immunoglobulin are the classical initial treatments for newly diagnosed ITP in adults, but these agents generally cannot induce a long-term response in most patients. Subsequent treatments for patients who fail the initial therapy include thrombopoietic agents, rituximab, fostamatinib, splenectomy, and several older immunosuppressive agents. Other potential therapeutic agents, such as inhibitors of Bruton's tyrosine kinase and neonatal Fc receptor, are currently under clinical evaluation. An optimized treatment strategy should aim at elevating the platelet counts to a safety level with minimal toxicity and improving patient health-related quality of life, and always needs to be tailored to the patients and disease phases. In this review, we address the concepts of adult ITP diagnosis and management and provide a comprehensive overview of current therapeutic strategies under general and specific situations.
Topics: Adult; Humans; Blood Platelets; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Thrombocytopenia
PubMed: 36658588
DOI: 10.1186/s13045-023-01401-z -
Anaesthesia Jan 2023Major haemorrhage is a leading cause of morbidity and mortality worldwide. Successful treatment requires early recognition, planned responses, readily available... (Review)
Review
Major haemorrhage is a leading cause of morbidity and mortality worldwide. Successful treatment requires early recognition, planned responses, readily available resources (such as blood products) and rapid access to surgery or interventional radiology. Major haemorrhage is often accompanied by volume loss, haemodilution, acidaemia, hypothermia and coagulopathy (factor consumption and fibrinolysis). Management of major haemorrhage over the past decade has evolved to now deliver a 'package' of haemostatic resuscitation including: surgical or radiological control of bleeding; regular monitoring of haemostasis; advanced critical care support; and avoidance of the lethal triad of hypothermia, acidaemia and coagulopathy. Recent trial data advocate for a more personalised approach depending on the clinical scenario. Fresh frozen plasma should be given as early as possible in major trauma in a 1:1 ratio with red blood cells until the results of coagulation tests are available. Tranexamic acid is a cheap, life-saving drug and is advocated in major trauma, postpartum haemorrhage and surgery, but not in patients with gastrointestinal bleeding. Fibrinogen levels should be maintained > 2 g.l in postpartum haemorrhage and > 1.5 g.l in other haemorrhage. Improving outcomes after major traumatic haemorrhage is now driving research to include extending blood-product resuscitation into prehospital care.
Topics: Female; Humans; Postpartum Hemorrhage; Hemorrhage; Male
PubMed: 36089857
DOI: 10.1111/anae.15866 -
Journal of Veterinary Emergency and... Mar 2021To use a systematic, evidence-based consensus process to develop definitions for transfusion reactions in dogs and cats.
Association of Veterinary Hematology and Transfusion Medicine (AVHTM) Transfusion Reaction Small Animal Consensus Statement (TRACS). Part 1: Definitions and clinical signs.
OBJECTIVE
To use a systematic, evidence-based consensus process to develop definitions for transfusion reactions in dogs and cats.
DESIGN
Evidence evaluation of the literature was carried out for identified transfusion reaction types in dogs and cats. Reaction definitions were generated based on synthesis of human and veterinary literature. Consensus on the definitions was achieved through Delphi-style surveys. Draft recommendations were made available through industry specialty listservs and comments were incorporated.
RESULTS
Definitions with imputability criteria were developed for 14 types of transfusion reactions.
CONCLUSIONS
The evidence review and consensus process resulted in definitions that can be used to facilitate future veterinary transfusion reaction research.
Topics: Animals; Cat Diseases; Cats; Consensus; Dog Diseases; Dogs; Practice Guidelines as Topic; Transfusion Medicine; Transfusion Reaction; Veterinary Medicine
PubMed: 33792171
DOI: 10.1111/vec.13044 -
Current Opinion in Gastroenterology May 2021This article reviews the most recent studies regarding the management of acute esophageal variceal haemorrhage. (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
This article reviews the most recent studies regarding the management of acute esophageal variceal haemorrhage.
RECENT FINDINGS
New randomized control trials and meta-analyses confirmed the role of early transjugular intrahepatic portosystemic shunt (TIPS) in the management of acute variceal haemorrhage in Child-Pugh C (10-13) and B patients with active bleeding. A recent randomized controlled trial focused on the duration of vasoactive therapy showed no difference between 2 and 5 days of octreotide. A randomized trial showed decreased use of blood products for the correction of coagulopathy using a thromboelastography-guided approach (vs. conventional parameters) as well as decreased bleeding rates when compared with standard of care. A meta-analysis found that for rescue of variceal bleeding, self-expanding metallic stents were more efficacious and safer than balloon tamponade. In addition, studies showed that Child-Pugh C patients and those with hepatic vein pressure gradient more than 20 were at the highest risk of treatment failure, while model for end-stage liver disease was highly predictive of in-hospital mortality.
SUMMARY
In patients with severe coagulopathy and uncontrolled bleeding, TEG-based transfusion strategies are recommended. Antibiotics should be used for all cirrhotic patients presenting with upper gastrointestinal bleeding, but should be tailored in accordance to local resistance patterns. Early TIPS for high-risk patients has been shown to have a significant survival benefit. Certain aspects of the management of variceal bleeding remain poorly studied such as the role of early TIPS in Child-B patients as well as strategies for rescue therapy in patients who are not TIPS candidates, and require further investigation.
Topics: End Stage Liver Disease; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Severity of Illness Index
PubMed: 33769373
DOI: 10.1097/MOG.0000000000000723 -
Journal of the American Heart... Jul 2020Direct oral anticoagulants (DOACs) have quickly become attractive alternatives to the long-standing standard of care in anticoagulation, vitamin K antagonist. DOACs are... (Review)
Review
Direct oral anticoagulants (DOACs) have quickly become attractive alternatives to the long-standing standard of care in anticoagulation, vitamin K antagonist. DOACs are indicated for prevention and treatment of several cardiovascular conditions. Since the first approval in 2010, DOACs have emerged as leading therapeutic alternatives that provide both clinicians and patients with more effective, safe, and convenient treatment options in thromboembolic settings. With the expanding role of DOACs, clinicians are faced with increasingly complex decisions relating to appropriate agent, duration of treatment, and use in special populations. This review will provide an overview of DOACs and act as a practical reference for clinicians to optimize DOAC use among common challenging scenarios. Topics addressed include (1) appropriate indications; (2) use in patients with specific comorbidities; (3) monitoring parameters; (4) transitioning between anticoagulant regimens; (5) major drug interactions; and (6) cost considerations.
Topics: Administration, Oral; Blood Coagulation; Clinical Decision-Making; Comorbidity; Cost-Benefit Analysis; Drug Costs; Drug Interactions; Drug Monitoring; Drug Substitution; Factor Xa Inhibitors; Hemorrhage; Humans; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32538234
DOI: 10.1161/JAHA.120.017559 -
Anesthesiology May 2023Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum...
Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.
Topics: Female; Humans; Anticoagulants; Blood Coagulation Disorders; Hemorrhage; Hemostatics; Platelet Aggregation Inhibitors; Postpartum Period
PubMed: 36862401
DOI: 10.1097/ALN.0000000000004520 -
Seminars in Thrombosis and Hemostasis Feb 2020Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than... (Review)
Review
Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than other coagulation factors. Although the critical minimum concentration of fibrinogen to maintain hemostasis is a matter of debate, many patients with coagulopathic bleeding require fibrinogen supplementation. Among the treatment options for fibrinogen supplementation, fibrinogen concentrate may be viewed by some as preferable to fresh frozen plasma or cryoprecipitate. The authors review major studies that have assessed fibrinogen treatment in trauma, cardiac surgery, end-stage liver disease, postpartum hemorrhage, and pediatric patients. Some but not all randomized controlled trials have shown that fibrinogen concentrate can be beneficial in these settings. The use of fibrinogen as part of coagulation factor concentrate based therapy guided by point-of-care viscoelastic coagulation monitoring (ROTEM [rotational thromboelastometry] or TEG [thromboelastography]) appears promising. In addition to reducing patients' exposure to allogeneic blood products, this strategy may reduce the risk of complications such as transfusion-associated circulatory overload, transfusion-related acute lung injury, and thromboembolic adverse events. Randomized controlled trials are challenging to perform in patients with critical bleeding, and more evidence is needed in this setting. However, current scientific rationale and clinical data support fibrinogen repletion in patients with ongoing bleeding and confirmed fibrinogen deficiency.
Topics: Blood Component Transfusion; Fibrinogen; Hemorrhage; Humans; Plasma; Point-of-Care Systems; Randomized Controlled Trials as Topic; Risk Factors; Thrombelastography; Transfusion-Related Acute Lung Injury
PubMed: 31574543
DOI: 10.1055/s-0039-1696946