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Chimeric Antigen Receptor T Cell Therapy in Acute Myeloid Leukemia: Trials and Tribulations 嵌合抗原受体T细胞治疗急性髓性白血病:试验和磨难
Pub Date : 2023-11-12 DOI: 10.3390/hematolrep15040063
Swati Garg, Wei Ni, James D. Griffin, Martin Sattler
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that is often associated with relapse and drug resistance after standard chemotherapy or targeted therapy, particularly in older patients. Hematopoietic stem cell transplants are looked upon as the ultimate salvage option with curative intent. Adoptive cell therapy using chimeric antigen receptors (CAR) has shown promise in B cell malignancies and is now being investigated in AML. Initial clinical trials have been disappointing in AML, and we review current strategies to improve efficacy for CAR approaches. The extensive number of clinical trials targeting different antigens likely reflects the genetic heterogeneity of AML. The limited number of patients reported in multiple early clinical studies makes it difficult to draw conclusions about CAR safety, but it does suggest that the efficacy of this approach in AML lags behind the success observed in B cell malignancies. There is a clear need not only to improve CAR design but also to identify targets in AML that show limited expression in normal myeloid lineage cells.
急性髓系白血病(AML)是一种异质性的血液系统恶性肿瘤,通常与标准化疗或靶向治疗后的复发和耐药有关,特别是在老年患者中。造血干细胞移植被认为是具有治疗目的的最终挽救选择。使用嵌合抗原受体(CAR)的过继细胞疗法在B细胞恶性肿瘤中显示出希望,目前正在研究AML。AML的初步临床试验结果令人失望,我们回顾了目前提高CAR疗法疗效的策略。针对不同抗原的大量临床试验可能反映了AML的遗传异质性。在多个早期临床研究中报告的患者数量有限,因此很难得出CAR安全性的结论,但它确实表明这种方法在AML中的疗效落后于在B细胞恶性肿瘤中观察到的成功。显然,不仅需要改进CAR的设计,而且还需要确定AML中在正常髓系细胞中表达有限的靶标。
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引用次数: 0
Management and Outcomes of Invasive Procedures in Individuals with Hemophilia A on Emicizumab Prophylaxis: A Single Center Experience Emicizumab预防的A型血友病患者侵入性治疗的管理和结果:单中心经验
Pub Date : 2023-11-01 DOI: 10.3390/hematolrep15040062
Karla Rener, Saša Anžej Doma, Martina Fink, Helena Podgornik, Irena Preložnik Zupan
Prophylactic treatment with emicizumab has become an important and effective bleeding prevention for people with hemophilia A (PwHA). Perioperative management of PwHA using emicizumab prophylaxis is still challenging due to a lack of experience. Medical records of perioperative management and outcomes were reviewed, and data were collected for adult PwHA receiving emicizumab and undergoing surgical procedures between August 2019 and July 2022 at the University Medical Center Ljubljana. Twelve surgical procedures were performed in eight PwHA (one with FVIII inhibitors) while on emicizumab prophylaxis. Three minor procedures included cataract surgery, cystoscopic lithotripsy, and percutaneous coronary intervention. Nine major surgeries included four osteosyntheses, necrectomy of chronic osteomyelitis with new ankle arthrodesis, two below-knee amputations, total knee replacement, and placement of ventriculostomy after a spontaneous intraventricular hemorrhage. No major bleeds, thrombotic events or deaths, or new inhibitors appeared. Our real-world experience demonstrates that minor and major surgeries can be performed safely in PwHA on emicizumab prophylaxis. Additional data are needed to optimize dosing/duration of additional hemostatic agents in diverse invasive procedures and complex clinical situations.
emicizumab预防性治疗已成为血友病A (PwHA)患者重要而有效的出血预防方法。由于缺乏经验,使用emicizumab预防PwHA的围手术期管理仍然具有挑战性。回顾了2019年8月至2022年7月在卢布尔雅那大学医学中心接受emicizumab并接受外科手术的成年PwHA围手术期管理和结果的医疗记录,并收集了数据。8例PwHA患者(1例使用FVIII抑制剂)在emicizumab预防期间进行了12次外科手术。三种小手术包括白内障手术、膀胱镜碎石术和经皮冠状动脉介入治疗。9次主要手术包括4次植骨、慢性骨髓炎伴新踝关节融合术的坏死切除、2次膝下截肢、全膝关节置换术和自发性脑室内出血后的脑室造口术。没有大出血、血栓事件或死亡,也没有出现新的抑制剂。我们的实际经验表明,在emicizumab预防下,PwHA患者可以安全地进行小手术和大手术。在不同的侵入性手术和复杂的临床情况下,需要更多的数据来优化其他止血药物的剂量/持续时间。
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引用次数: 0
Effect of antiepileptic drugs on plasma fibrinogen level 抗癫痫药物对血浆纤维蛋白原水平的影响
Pub Date : 2020-05-07 DOI: 10.4081/hr.2020.7952
R. El-Ashry, M. M. El-Ayuoty, H. Azzam, M. A. El-Naggar
Background: Childhood epilepsy is one of the most common neurological disorders in pediatrics . The prevalence of active epilepsy is 5–8 per 1000 population in developed countries and 10 per 1000 population in developing nations . There is a significant relationship between epilepsy and cognitive deficits. Aim of study: prospective study to evaluate the effect of the most commonly used anti-epileptics drugs on plasma fibrinogen level. Patient and methods 100 newly diagnosed patients (2months to 15 years old) selected from Outpatient Clinic of Neurology attending Mansoura University Children’s Hospital for plasma fibrinogen level evaluation by taking basal sample and second sample after six months after the basal one. Results: This study showed that, significant positive correlation between plasma fibrinogen level and the use of antiepileptic drugs. Conclusion: epileptic patient should be closely monitored during Antiepileptic drugs treatment and prior to surgical procedures as they can affect plasma fibrinogen level and coagulation profile. INTRODUCTION Epilepsy is a common illness worldwide. It is estimated that 0.5-1% of all children have epilepsy, with the majority presenting during infancy or early childhood (1). Epileptic seizures result from abnormal, excessive or hypersynchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy, and nearly 80% of epilepsy occurs in developing countries(2 ). Antiepileptic drugs (AED) have been associated with adverse effects on the coagulation system. Carbamazepine, phenytoin and valproic acid can cause thrombocytopenia , Additionally, valproic acid and gabapentin have been associated with acquired von Willebrand disease type 1, hypofibrinogenemia ,decreased factorXIII and abnormal platelet function. (3). Coagulopathies were reported in children treated with VPA (>4%), but this is likely to be significantly underestimated. These children were reported with platelet dysfunction, thrombocytopenia, hypofibrinogenemia, acquired Von Wilbrand disease, Factor XIII deficiency and vitamin K-dependent factor deficiency (4). Little is known about the hematological side effects of the newer antiepileptic drugs (AEDs), but recent case reports have raised concerns regarding the possibility of altered coagulation profile, thrombocyte counts or function in some patients during levetiracetam (LEV) treatment. .( 5) Carbmazepines have been reported to be associated with clotting defects including: elevated prothrombin time, elevated partial thromboplastin time, though the exact mechanism is not known yet (6). PATIENT AND METHODS In this Observational Prospective Study, One hundred newly diagnosed patients will be included. They will be selected from the patients attended to Mansoura University Children Hospital at Outpatient Clinic of Neurology. This study was conducted on One hundred newly diagnosed patients with age ranging from 2 months to 15 years. In This study, we search for plasma fibrino
背景:儿童癫痫是儿科最常见的神经系统疾病之一。活动性癫痫的患病率在发达国家为每1000人中5-8人,在发展中国家为每1000人中10人。癫痫和认知缺陷之间有显著的关系。研究目的:前瞻性研究最常用的抗癫痫药物对血浆纤维蛋白原水平的影响。患者与方法选取曼苏拉大学儿童医院神经内科门诊新确诊患者100例(年龄2个月~ 15岁),采用基础取样法和基础取样后6个月第二次取样法测定血浆纤维蛋白原水平。结果:血浆纤维蛋白原水平与抗癫痫药物的使用有显著正相关。结论:癫痫患者在抗癫痫药物治疗期间及手术前应密切监测其血浆纤维蛋白原水平及凝血特征。癫痫是世界范围内的一种常见病。据估计,所有儿童中有0.5-1%患有癫痫,多数出现在婴儿期或幼儿期(1)。癫痫发作是由大脑中异常、过度或超同步的神经元活动引起的。全世界约有5000万人患有癫痫,近80%的癫痫发生在发展中国家(2)。抗癫痫药物(AED)与凝血系统的不良反应有关。卡马西平、苯妥英和丙戊酸可引起血小板减少,此外,丙戊酸和加巴喷丁与获得性血管性血友病1型、低纤维蛋白原血症、因子xiii降低和血小板功能异常有关。(3)在接受VPA治疗的儿童中有凝血功能障碍的报道(>4%),但这可能被严重低估了。据报道,这些儿童患有血小板功能障碍、血小板减少症、低纤维蛋白原血症、获得性血管性血友病、因子XIII缺乏症和维生素k依赖性因子缺乏症(4)。关于新型抗癫痫药物(aed)的血液学副作用知之甚少,但最近的病例报告引起了人们对凝血功能改变的可能性的关注。(5)据报道,卡马西平与凝血缺陷相关,包括:凝血酶原时间升高,部分凝血活酶时间升高,尽管确切的机制尚不清楚(6)。患者和方法在这项观察性前瞻性研究中,将包括100名新诊断的患者。他们将从曼苏拉大学儿童医院神经内科门诊就诊的患者中挑选。本研究对100名年龄在2个月至15岁之间的新诊断患者进行了研究。在这项研究中,我们寻找血浆纤维蛋白原水平和凝血谱。我们做了一个基础样本然后在开始抗癫痫治疗六个月后进行另一个随访样本。纳入标准:1;根据癫痫标准新诊断为癫痫的儿童,至少两次非诱发性(或反射性)癫痫发作间隔大于24小时。1次非诱发性(或反射性)发作,在未来10年内再次发作的概率与两次非诱发性发作后的一般复发风险相似(至少60%)。2. 所有患者身体健康,无出血或血栓病史。3.患者将接受抗癫痫药物治疗。排除标准:•影响纤维蛋白原的血液学问题[弥散性血管内凝血,溶血性尿毒症综合征]。•已知患有肾脏或肝脏疾病的患者。•接受其他影响凝血功能药物(水杨酸盐或抗凝剂)的患者。
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引用次数: 0
Immunoistochemical expression of PD-1 and PD-L1 in bone marrow biopsies of patients with acute myeloid leukemia 急性髓性白血病患者骨髓活检组织中PD-1和PD-L1的免疫组化表达
Pub Date : 2020-05-07 DOI: 10.4081/hr.2020.8211
Francesco Romano, A. Giannone, S. Siragusa, R. Porcasi, A. Florena
Author’s contributions: Francesco Romano conceived, designed and performed the experiment, analyzed the data and wrote the manuscript. Antonino Giulio Giannone designed the experiment, analyzed the data and designed the figures. Sergio Siragusa wrote and revised the manuscript. Rossana Porcasi performed the experiment and analyzed the data. Ada Maria Florena provided the samples, wrote and revised the manuscript.
作者贡献:Francesco Romano构思,设计和执行实验,分析数据并撰写手稿。Antonino Giulio Giannone设计了实验,分析了数据并设计了图表。Sergio Siragusa撰写并修改了手稿。罗萨娜·波尔卡西进行了实验并分析了数据。Ada Maria Florena提供了样本,撰写并修改了手稿。
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引用次数: 0
Biological role of immunoglobulin Free light chains interactomes 免疫球蛋白游离轻链相互作用组的生物学作用
Pub Date : 2015-01-01 DOI: 10.4081/hr.2015.5946
G. Noto, A. Bugatti, Michela Bertuzzi, Alessandra Dossi, F. Maffina, L. Paolini, A. Radeghieri, L. Caimi, M. Rusnati, D. Ricotta
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引用次数: 1
10th International Winter Meeting on Coagulation. Basic, Laboratory and Clinical Aspects of Venous and Arterial Thromboembolic Diseases. Bormio, Italy, April 10-16, 2011 第十届国际凝血冬季会议。静脉和动脉血栓栓塞性疾病的基础、实验室和临床方面。2011年4月10日至16日,意大利博尔米奥
Pub Date : 2012-11-12 DOI: 10.4081/HR.2011.S1
A. Girolami, C. Esmon, M. Cattaneo, A. Spyropoulos, F. Piovella
10th International Winter Meeting on Coagulation,Basic, Laboratory and Clinical Aspects of Venous and Arterial Thromboembolic Diseases Bormio, April 10-16, 2011. With the auspices of ALT (Associazione per la Lotta alla Trombosi e alle malattie cardiovascolari – Onlus) FCSA (Federazione Centri per la diagnosi della trombosi e la Sorveglianza delle terapie Antitrombotiche) SISET (Societa Italiana per lo Studio della Emostasi e della Trombosi) Scientific Committee Armando D’Angelo (Milano, Italy), Antonio Girolami (Padova, Italy), Charles T. Esmon (Oklahoma City, OK, USA), Marco Cattaneo (Milano, Italy), Alexander Spyropoulos (Hamilton, ON, Canada) Franco Piovella (Pavia, Italy)
2011年4月10日至16日。协会With the auspices of ALT(心血管血栓形成和抗击疾病—中心联合会(欢迎)FCSA血栓的诊断和治疗监测Antitrombotiche) SISET(意大利社会研究Emostasi和血栓形成)科学委员会的武装分支(米兰、意大利)、安东尼奥·Girolami(帕多瓦、意大利),查尔斯·T . Esmon(俄克拉荷马城,好吧,美国)、卡塔(米兰、意大利)、亚历山大·马克Spyropoulos(汉密尔顿,,(加拿大)弗朗哥·皮奥维拉(意大利帕维亚)
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引用次数: 0
Confirmation of the validity of using birth MCV for the diagnosis of alpha thalassemia trait 确认使用出生MCV诊断α地中海贫血特征的有效性
Pub Date : 2009-07-01 DOI: 10.4081/hr.2009.e20
A. Al-Hilali, Aisha M. Al-Jallaf, Sajida Chunkasseril
Thirty-four blood samples of neonates in Dubai, UAE, with an MCV below 90 fL were checked by high performance liquid chromatography (HPLC) for hemoglobin variants to confirm a previous study carried out in Western Province of Saudi Arabia which showed a very high predictive index of such MCV for alpha (α-) thalassemia minor (ATM). MCH below 30 pg was an additional factor which supported such a prediction. The Dubai study confirmed the original finding with 100% of such neonates showing Hb Barts band. A control group of 26 neonates with an MCV between 90 and 95 fl showed Hb Barts in only 11 cases (42.3%). Of these, 6 (23.1%) were preterm babies, expected to have higher MCV. Five cases (19.2%) had an MCH below 30 pg, though MCV was 90 or higher. Three of the preterm babies also had MCH below 30. The study confirmed the Saudi results in neonates. It seems very highly probable that a term neonate with MCV below 90 and MCH below 30 has ATM.
本文采用高效液相色谱法(HPLC)检测了阿联酋迪拜34例MCV低于90 fL的新生儿血液样本中的血红蛋白变异,以证实先前在沙特阿拉伯西部省进行的一项研究,该研究显示MCV对α (α-)轻度地中海贫血(ATM)具有非常高的预测指数。MCH低于30 pg是支持这一预测的另一个因素。迪拜的研究证实了最初的发现,100%的新生儿显示Hb Barts带。对照组26例MCV在90 - 95 fl之间的新生儿中,仅有11例(42.3%)出现Hb Barts。其中6例(23.1%)为早产儿,预计MCV较高。5例(19.2%)MCH低于30 pg,但MCV为90或更高。其中3名早产儿的MCH也低于30。这项研究在新生儿中证实了沙特的结果。MCV低于90,MCH低于30的足月新生儿似乎极有可能患有ATM。
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引用次数: 2
Best practices for transfusion for patients with sickle cell disease 镰状细胞病患者输血的最佳做法
Pub Date : 2009-07-01 DOI: 10.4081/hr.2009.e22
T. Wun, K. Hassell
The β-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC) can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD) Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research. A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.
镰状细胞性贫血的β-珠蛋白基因突变导致贫血和反复发作的血管闭塞。这些血管阻塞事件的累积效应是对许多器官的进行性损害,包括肾、肺和脑。红细胞(RBC)的输血可以改善许多并发症,但可能与急性和慢性并发症有关,包括铁超载。镰状细胞病(SCD)患者输血医学最佳实践会议的目的是由一个专家小组审查有关镰状细胞病使用红细胞输血的现有已发表证据和临床经验。专家小组为SCD患者使用红细胞制定了明确的临床指南。该小组还提出了进一步研究的建议。制定了一套准则,以便向有关利益攸关方散发。如果实施,这些临床途径有可能优化SCD中红细胞输注的使用。
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引用次数: 28
A case of follicular lymphoma complicated with mesenteric panniculitis 滤泡性淋巴瘤合并肠系膜膜炎1例
Pub Date : 2009-07-01 DOI: 10.4081/hr.2009.e17
Y. Tamai, O. Imataki, I. Ito, K. Kawakami
Mesenteric panniculitis (MP) is a rare disease occasionally complicated with lymphoma. A 55-year old female presented with MP accompanied by malignant lymphoma. This patient was first treated for follicular lymphoma and subsequently for panniculitis. After 6 courses of R-CHOP chemotherapy, the treatment response was partial. An additional course of salvage chemotherapy led to a complete response. Since the mesenteric mass progressed simultaneously with the regression of other lymphoma lesions, we performed a biopsy of the mesenteric mass and pathologically confirmed an MP lesion without lymphoma. Subsequent high-dose chemotherapy led to CR and the MP lesion remained stable. In the present case, MP progressed with chemotherapy. We concluded that mesenteric lesions suspected of progressing or recurring should be diagnosed pathologically even if asymptomatic.
摘要肠系膜膜炎是一种罕见的疾病,偶尔会并发淋巴瘤。一位55岁女性,表现为MP伴恶性淋巴瘤。该患者最初因滤泡性淋巴瘤而接受治疗,随后因睫状体炎而接受治疗。经6个疗程的R-CHOP化疗后,治疗效果为部分缓解。一个额外的补救性化疗疗程导致完全缓解。由于肠系膜肿块与其他淋巴瘤病变同时进展,我们对肠系膜肿块进行了活检,病理证实为无淋巴瘤的MP病变。随后的大剂量化疗导致CR和MP病变保持稳定。在本病例中,MP随着化疗进展。我们的结论是,肠系膜病变怀疑进展或复发应病理诊断,即使无症状。
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引用次数: 8
Massive pleural effusion due to IgG multiple myeloma IgG多发性骨髓瘤所致大量胸腔积液
Pub Date : 2009-07-01 DOI: 10.4081/hr.2009.e18
K. Lang, S. Lidder, R. Aitchison
Pleural effusion directly attributable to multiple myeloma is exceedingly uncommon and is said to occur in only 1–2% of cases. Of these around 80% occur in IgA disease. We report a case of myelomatous pleural effusion (proven on cytological and immunohistochemical analysis) in a patient with the IgG-κ subtype. We describe the diagnosis, pathogenesis and management of this condition and show the radiological and cytological evidence of the case.
直接由多发性骨髓瘤引起的胸腔积液是非常罕见的,据说只有1-2%的病例发生。其中约80%发生在IgA疾病中。我们报告一例骨髓瘤性胸腔积液(经细胞学和免疫组织化学分析证实),患者为IgG-κ亚型。我们描述的诊断,发病机制和管理这种情况,并显示放射学和细胞学证据的情况下。
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引用次数: 7
期刊
Hematology Reviews
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