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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 -
JAMA Feb 2015Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials.
OBJECTIVE
To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio.
DESIGN, SETTING, AND PARTICIPANTS
Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013.
INTERVENTIONS
Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled).
MAIN OUTCOMES AND MEASURES
Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status.
RESULTS
No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications.
CONCLUSIONS AND RELEVANCE
Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01545232.
Topics: Blood Component Transfusion; Blood Platelets; Erythrocytes; Exsanguination; Female; Hemostasis; Humans; Male; Plasma; Shock, Hemorrhagic; Wounds and Injuries
PubMed: 25647203
DOI: 10.1001/jama.2015.12 -
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 -
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 -
Nature Reviews. Neurology Jul 2017Intracerebral haemorrhage (ICH) is the most lethal subtype of stroke but currently lacks effective treatment. Microglia are among the first non-neuronal cells on the... (Review)
Review
Intracerebral haemorrhage (ICH) is the most lethal subtype of stroke but currently lacks effective treatment. Microglia are among the first non-neuronal cells on the scene during the innate immune response to ICH. Microglia respond to acute brain injury by becoming activated and developing classic M1-like (proinflammatory) or alternative M2-like (anti-inflammatory) phenotypes. This polarization implies as yet unrecognized actions of microglia in ICH pathology and recovery, perhaps involving microglial production of proinflammatory or anti-inflammatory cytokines and chemokines. Furthermore, alternatively activated M2-like microglia might promote phagocytosis of red blood cells and tissue debris, a major contribution to haematoma clearance. Interactions between microglia and other cells modulate microglial activation and function, and are also important in ICH pathology. This Review summarizes key studies on modulators of microglial activation and polarization after ICH, including M1-like and M2-like microglial phenotype markers, transcription factors and key signalling pathways. Microglial phagocytosis, haematoma resolution, and the potential crosstalk between microglia and T lymphocytes, neurons, astrocytes, and oligodendrocytes in the ICH brain are described. Finally, the clinical and translational implications of microglial polarization in ICH are presented, including the evidence that therapeutic approaches aimed at modulating microglial function might mitigate ICH injury and improve brain repair.
Topics: Animals; Astrocytes; Cerebral Hemorrhage; Cytokines; Humans; Microglia; Oligodendroglia; T-Lymphocytes
PubMed: 28524175
DOI: 10.1038/nrneurol.2017.69 -
JAMA Aug 2016Acute aortic syndrome (AAS), a potentially fatal pathologic process within the aortic wall, should be suspected in patients presenting with severe thoracic pain and... (Review)
Review
IMPORTANCE
Acute aortic syndrome (AAS), a potentially fatal pathologic process within the aortic wall, should be suspected in patients presenting with severe thoracic pain and hypertension. AAS, including aortic dissection (approximately 90% of cases) and intramural hematoma, may be complicated by poor perfusion, aneurysm, or uncontrollable pain and hypertension. AAS is uncommon (approximately 3.5-6.0 per 100,000 patient-years) but rapid diagnosis is imperative as an emergency surgical procedure is frequently necessary.
OBJECTIVE
To systematically review the current evidence on diagnosis and treatment of AAS.
EVIDENCE REVIEW
Searches of MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials for articles on diagnosis and treatment of AAS from June 1994 to January 29, 2016, were performed. Only clinical trials and prospective observational studies of 10 or more patients were included. Eighty-two studies (2 randomized clinical trials and 80 observational) describing 57,311 patients were reviewed.
FINDINGS
Chest or back pain was the most commonly reported presenting symptom of AAS (61.6%-84.8%). Patients were typically aged 60 to 70 years, male (50%-81%), and had hypertension (45%-100%). Sensitivities of computerized tomography and magnetic resonance imaging for diagnosis of AAS were 100% and 95% to 100%, respectively. Transesophageal echocardiography was 86% to 100% sensitive, whereas D-dimer was 51.7% to 100% sensitive and 32.8% to 89.2% specific among 6 studies (n = 876). An immediate open surgical procedure is needed for dissection of the ascending aorta, given the high mortality (26%-58%) and proximity to the aortic valve and great vessels (with potential for dissection complications such as tamponade). An RCT comparing endovascular surgical procedure to medical management for uncomplicated AAS in the descending aorta (n = 61) revealed no dissection-related deaths in either group. Endovascular surgical procedure was better than medical treatment (97% vs 43%, P < .001) for the primary end point of "favorable aortic remodeling" (false lumen thrombosis and no aortic dilation or rupture). The remaining evidence on therapies was observational, introducing significant selection bias.
CONCLUSIONS AND RELEVANCE
Because of the high mortality rate, AAS should be considered and diagnosed promptly in patients presenting with acute chest or back pain and high blood pressure. Computerized tomography, magnetic resonance imaging, and transesophageal echocardiography are reliable tools for diagnosing AAS. Available data suggest that open surgical repair is optimal for treating type A (ascending aorta) AAS, whereas thoracic endovascular aortic repair may be optimal for treating type B (descending aorta) AAS. However, evidence is limited by the paucity of randomized trials.
Topics: Acute Disease; Aged; Aortic Dissection; Aortic Aneurysm; Aortic Diseases; Back Pain; Chest Pain; Fibrin Fibrinogen Degradation Products; Hematoma; Humans; Hypertension; Magnetic Resonance Imaging; Male; Medical Illustration; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 27533160
DOI: 10.1001/jama.2016.10026 -
Journal of Thrombosis and Haemostasis :... Apr 2005Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between...
Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta-analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non-surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.
Topics: Anticoagulants; Fibrinolytic Agents; Hematology; Hemorrhage; Hemostasis; Humans; Platelet Aggregation Inhibitors; Postoperative Complications
PubMed: 15842354
DOI: 10.1111/j.1538-7836.2005.01204.x -
Clinical and Applied... Jul 2017Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability,... (Review)
Review
Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4.5 to 10 in patients with other risk factors for bleeding. Fresh frozen plasma or prothrombin complex concentrate (PCC) may be necessary in major bleeding related to warfarin. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors. The PCC may reverse the effect of rivaroxaban to some extent, but no data are available regarding reversal of apixaban and edoxaban. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Blood Coagulation Factors; Blood Coagulation Tests; Hemorrhage; Humans; International Normalized Ratio; Plasma; Protamines
PubMed: 27789605
DOI: 10.1177/1076029616675970 -
Journal of Cancer Research and Clinical... Aug 2023Artificial intelligence (AI) is influencing our society on many levels and has broad implications for the future practice of hematology and oncology. However, for many... (Review)
Review
BACKGROUND
Artificial intelligence (AI) is influencing our society on many levels and has broad implications for the future practice of hematology and oncology. However, for many medical professionals and researchers, it often remains unclear what AI can and cannot do, and what are promising areas for a sensible application of AI in hematology and oncology. Finally, the limits and perils of using AI in oncology are not obvious to many healthcare professionals.
METHODS
In this article, we provide an expert-based consensus statement by the joint Working Group on "Artificial Intelligence in Hematology and Oncology" by the German Society of Hematology and Oncology (DGHO), the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), and the Special Interest Group Digital Health of the German Informatics Society (GI). We provide a conceptual framework for AI in hematology and oncology.
RESULTS
First, we propose a technological definition, which we deliberately set in a narrow frame to mainly include the technical developments of the last ten years. Second, we present a taxonomy of clinically relevant AI systems, structured according to the type of clinical data they are used to analyze. Third, we show an overview of potential applications, including clinical, research, and educational environments with a focus on hematology and oncology.
CONCLUSION
Thus, this article provides a point of reference for hematologists and oncologists, and at the same time sets forth a framework for the further development and clinical deployment of AI in hematology and oncology in the future.
Topics: Humans; Artificial Intelligence; Medical Oncology; Hematology; Forecasting
PubMed: 36920563
DOI: 10.1007/s00432-023-04667-5 -
Critical Care (London, England) Jul 2023Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this... (Review)
Review
BACKGROUND
Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT.
METHODS
We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure.
RESULTS
Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5).
CONCLUSIONS
Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
Topics: Adult; Humans; Hemorrhage; Hemostatics; Blood Transfusion; Blood Platelets; Erythrocyte Transfusion
PubMed: 37407998
DOI: 10.1186/s13054-023-04537-z