Acute leukemia

急性白血病
  • 文章类型: Journal Article
    急性白血病是白细胞的一种癌症,其进展迅速且剧烈。有两种类型:急性淋巴细胞白血病(ALL)和急性髓细胞性白血病(AML)。后者具有罕见的亚型:急性早幼粒细胞白血病(APL)。对一些病人来说,一线治疗后,没有达到缓解(“难治性疾病”),对其他人来说,白血病在达到缓解后复发(“复发”)。对于这些人来说,结果通常很差。是的,因此,在这种情况下,了解患者的治疗重点很重要。
    建立在形成性定性研究的基础上,我们设计了一项包含离散选择实验(DCE)的在线调查,以探索患者在复发/难治情况下的治疗偏好.DCE属性是给药方式;治疗期间的生活质量;应答机会;应答持续时间;和应答期间的生活质量。每个受访者完成了包含两个假设治疗的十二个方案。如果参与者居住在英国并被诊断为急性白血病,则他们符合资格。使用潜在类模型对数据进行了分析。
    共有95名患者完成了调查。潜在的类分析确定了两个类。对于两者来说,响应的机会是最重要的属性。对于1级,每个属性都很重要,而对于2类,唯一重要的属性是生活质量(治疗和应答期间)和应答机会.总体来说,更大比例的受访者将属于第一类,患有ALL或APL的人以及最近被诊断出的人更有可能处于2级。
    我们的结果表明,患者强烈关注反应的机会,以及生活质量(在较小程度上),当在复发/难治性环境中面临不同的治疗选择时。然而,患者群体内存在显著的偏好异质性,和其他治疗特征对许多人也很重要。
    UNASSIGNED: Acute leukemia is a cancer of the white blood cells which progresses rapidly and aggressively. There are two types: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The latter has a rare subtype: acute promyelocytic leukemia (APL). For some patients, following first-line treatment, remission is not achieved (\"refractory disease\"), and for others the leukemia returns after achieving remission (\"relapse\"). For these individuals, outcomes are typically poor. It is, therefore, important to understand patients\' treatment priorities in this context.
    UNASSIGNED: Building upon formative qualitative research, an online survey containing a discrete choice experiment (DCE) was designed to explore patients\' treatment preferences in the relapsed/refractory setting. The DCE attributes were mode of administration; quality of life during treatment; chance of response; duration of response; and quality of life during response. Each respondent completed twelve scenarios containing two hypothetical treatments. Participants were eligible if they lived in the United Kingdom and had a diagnosis of acute leukemia. The data were analysed using a latent class model.
    UNASSIGNED: A total of 95 patients completed the survey. The latent class analysis identified two classes. For both, chance of response was the most important attribute. For class 1, every attribute was important, whereas for class 2, the only important attributes were quality of life (during treatment and response) and chance of response. A greater proportion of respondents would fall into class 1 overall, and those with ALL or APL and those more recently diagnosed were more likely to be in class 2.
    UNASSIGNED: Our results indicate that patients are strongly concerned about the chance of response, as well as quality of life (to a lesser extent), when faced with different treatment options in the relapsed/refractory setting. However, there is significant preference heterogeneity within the patient population, and other treatment characteristics also matter to many.
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  • 文章类型: Journal Article
    18F-FDGPET成像可以揭示白血病患者的主要发现是急性或慢性形式的骨髓(BM)浸润。这种能力可以影响和指导BM活检的使用,但也可以评估治疗反应。此外,据报道,18F-FDGPET成像特别适用于诊断具有非特异性症状的患者的白血病。在急性白血病的情况下,它还揭示了评估髓外形式的作用,而在慢性形式的情况下,已报道了评估里氏转化的作用。
    The main finding that 18F-FDG PET imaging can reveal in patients with leukemias is the presence of bone marrow (BM) infiltration in both acute or chronic forms. This ability can influence and guide the use of BM biopsy but also assess to therapy response. Additionally 18F-FDG PET imaging has been reported as particularly useful for the diagnosis of leukemias in patients with non specific symptoms. In the case of acute leukemias it revealed also a role for the evaluation of extramedullary forms while in the case of chronic forms a role for the assessment of Richter transformation has been reported.
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  • 文章类型: Case Reports
    混合表型急性白血病(MPAL)是一种罕见的白血病,谱系不清,根据正式标准准确诊断这个实体存在挑战。在这里,我们报告了一例根据非典型外周血流式细胞术最初诊断为“AML”的病例,随后根据骨髓结果确定为B-ALL并进行KMT2A重排。尽管KMT2A重排代表了谱系模糊的急性白血病的定义遗传异常,该病例不符合基于WHO2022标准的MPAL标准.此案例突出了MPAL的诊断挑战以及当前分类的潜在局限性。我们讨论了这些患者的最合适的检查和管理,并确定了未来研究的领域。
    Mixed-phenotype acute leukemia (MPAL) is a rare form of leukemia with ambiguous lineage, and there are challenges in accurately diagnosing this entity according to formal criteria. Here we report a case which was initially diagnosed as \"AML\" based on atypical peripheral blood flow cytometry that was subsequently determined to be B-ALL with KMT2A rearrangement based on marrow results. Although KMT2A rearrangements represent a defining genetic abnormality for acute leukemia of ambiguous lineage, this case did not meet the criteria for MPAL based on WHO 2022 criteria. This case highlights the diagnostic challenges of MPAL and the potential limitations of the current classification. We discuss the most appropriate workup and management of these patients and identify areas for future study.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    PICALM:MLLT10融合基因是急性白血病(AL)中罕见但复发的事件,与不良预后相关。PICALM::MLLT10是否可以仅对应于急性髓细胞性白血病(AML)或急性淋巴细胞性白血病(ALL)或谱系模糊的急性白血病(ALAL),仍然令人困惑。这里,我们报道了一系列PICALM::MLLT10阳性AL患者的各种免疫表型包括T-ALL,ALAL,AML,B-ALL,复杂核型,一半的髓外疾病(EMD),经常伴随PHF6突变,对针对不同免疫表型的标准化疗的初始治疗反应差,但对联合化疗特别是与维奈托克的联合化疗表现出敏感性,提示此融合基因可能提示AL的新亚群。在我们中心通过RNA测序鉴定了533例AL患者中的18例MLLT10阳性患者(18/533,3.4%)。我们发现PICALM::MLLT10阳性AL显示各种免疫表型,白血病干性基因的高表达和维奈托克耐药的生物标志物的低表达,更多的髓外参与,尤其是对常规诱导化疗的反应不佳,但可能受益于维奈托克和低剂量的阿拉-C,粒细胞集落刺激因子(G-CSF),和蒽环类药物联合化疗。化疗后序贯造血干细胞移植(HSCT)联合维奈托克可进一步提高完全缓解(CR)甚至可测量的残留病(MRD)阳性的AL患者的长期生存率。
    The PICALM::MLLT10 fusion gene is a rare but recurrent event in acute leukemia (AL) associated with poor prognosis. It is still confused whether PICALM::MLLT10 can solely correspond to acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or acute leukemias of ambiguous lineage (ALAL). Here, we reported a series of PICALM::MLLT10 positive AL patients with miscellaneous immunophenotype including T-ALL, ALAL, AML, and B-ALL, complex karyotype, half of extramedullary disease (EMD), frequently concomitant PHF6 mutation, and poor initial treatment response to standard chemotherapy aiming to different immunophenotype, but showing sensitivity to combining chemotherapy especially integrated with venetoclax, suggesting this fusion gene may indicate a new subgroup of AL. Eighteen PICALM::MLLT10 positive patients of 533 AL patients (18/533, 3.4%) were identified by RNA sequencing in our center. We found PICALM::MLLT10 positive AL showing miscellaneous immunophenotype, higher expression of leukemic stemness genes and lower expression of biomarkers of venetoclax resistance, more extramedullary involvement, and especially poor response to conventional induction chemotherapy, but may benefit from venetoclax as well as low-dose Ara-C, granulocyte colony-stimulating factor (G-CSF), and anthracyclines combination chemotherapy. Sequential hematopoietic stem cell transplantation (HSCT) after chemotherapy combined with venetoclax may further improve long-term survival in AL patients with complete remission (CR) even measurable residual disease (MRD) positive.
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  • 文章类型: Journal Article
    使用移植后环磷酰胺(Cy后)的单倍体干细胞移植(haplo-SCT)被认为是缺乏匹配供体或由于高风险疾病而迫切需要移植程序的患者的合理治疗选择。我们分析了2018-2023年进行的haplo-SCT的结果。在大多数情况下,中位年龄为52岁的81名患者(46名男性)接受了使用外周血作为干细胞来源的单倍体SCT。适应症包括血液恶性肿瘤(88%的病例为急性白血病)。在25例(31%)中,复发/难治性疾病进行了移植。大多数患者(61%)表现出非常高的疾病风险指数(DRI)。调理方案如下:非清髓性-46例(57%),清髓性-在18(22%)和降低强度-17(20%)。90%的患者移植。所有患者均接受统一的免疫抑制治疗(Cy/TAC/MMF后)。中位随访时间为12个月,急性和慢性GVHD的累积发生率分别为37.5%和37.6%,分别。估计2年总生存率(OS)为43.1%,供体年龄是影响生存率的唯一因素。2年无进展生存率(PFS)为42.5%,而复发率(RI)-35%。非复发死亡率(NRM)的累积发生率为44%,主要是由于感染。Haplo-SCT是血液学患者可行的治疗选择。年轻的捐赠者提高了移植后的存活率。降低感染相关死亡率和复发率的策略仍然是一个挑战。
    Haploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018-2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relapsed/refractory disease. Majority of patients (61%) presented with very high and high disease risk index (DRI). Conditioning regimens were as follows: nonmyeloablative - 46 cases (57%), myeloablative - in 18 (22%) and reduced intensity - 17(20%). 90% of patients engrafted. All patients received unified immunosuppressive treatment (post-Cy/TAC/MMF). Median follow-up time was 12 months The cumulative incidence of acute and chronic GVHD was 37.5% and 37.6%, respectively. Estimated 2-year overall survival (OS) was 43.1% and donor\'s age was the only factor influencing survival. The 2-year progression-free survival (PFS) was 42.5%, whereas relapse incidence (RI) - 35%. The cumulative incidence of non-relapse mortality (NRM) was 44% and was mostly due to infections. Haplo-SCT is a feasible treatment option for hematological patients. Younger donor improves post-transplant survival. Strategies to reduce infection-related mortality and relapse rate remain a challenge.
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  • 文章类型: Journal Article
    背景:COVID-19感染对血液系统的影响尚待研究,尤其是那些遇到血液恶性肿瘤的患者.研究发现,很高比例的癌症患者面临COVID-19感染的风险较高。白血病患者通常受到抑制和免疫功能低下,这会影响COVID-19感染后的病理。因此,本研究旨在为COVID-19感染影响急性白血病患者血液学和生化指标的机制提供有价值的见解.
    方法:这项回顾性调查使用重复措施来检查沙特主要三级中心的急性白血病患者在COVID-19感染前后的血液学和生化参数变化。调查是在利雅得的国民警卫队卫生事务部进行的,沙特阿拉伯,2020年4月至2023年7月期间,24名患有COVID-19的急性白血病患者。COVID-19对临床参数的影响,合并症,和实验室值使用从四个指定时间间隔的电子健康记录中获得的数据进行评估。合并症的相对重要性,测试偏好,并确定了生存的重要预测因子。
    结果:大多数感染COVID-19的白血病患者,主要通过PCR检测,被诊断为急性淋巴细胞白血病(70.8%)。血液学和生化参数表现出稳定性,除了ALT的短暂增加和AST的持续上升。这些变化没有统计学意义,和参数在所有时间点保持正常。此外,在时间点-3显示单核细胞计数增加,在时间点2显示血小板计数增加.
    结论:虽然本研究未发现COVID-19对急性白血病患者生化和血液学参数的显著影响,需要进一步调查以充分了解COVID-19感染后的潜在不良反应和修饰.
    BACKGROUND: The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia.
    METHODS: This retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained.
    RESULTS: The majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2.
    CONCLUSIONS: While this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.
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  • 文章类型: Journal Article
    急性阑尾炎(AA)在小儿急性白血病患者中要求及时治疗。诊断带来挑战,依靠临床和放射学评估,往往导致治疗延误,可能扰乱白血病管理。我们对14例此类病例的研究强调了迅速干预的关键作用。虽然保守的AA治疗可能对健康儿童没有风险,我们的发现要求在诊断后24小时内进行腹腔镜阑尾切除术.该策略产生了成功的手术结果,同时确保不间断的白血病护理。我们的经验为导航这个复杂的临床场景的有限理解提供了重要的见解。
    Acute appendicitis (AA) in pediatric patients with acute leukemia mandates prompt treatment. Diagnosis presents challenges, relying on clinical and radiological assessments, often leading to treatment delays that may disrupt leukemia management. Our study on 14 such cases underscores the pivotal role of swift intervention. While conservative AA treatment may pose no risk to healthy children, our findings mandate the performance of laparoscopic appendectomy within 24 hours of diagnosis. This strategy yielded successful surgical outcomes while ensuring uninterrupted leukemia care. Our experience contributes important insights to the limited understanding of navigating this complex clinical scenario.
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  • 文章类型: Journal Article
    FAT1的缺失和过表达发生在不同的癌症中,这些不同的状态等同于肿瘤抑制和癌基因活性,分别。关于后者,FAT1在人类急性白血病中相对于正常血细胞高表达,有证据表明有致癌作用.我们假设这种情况代表FAT1在未定义的造血前体亚群中的传统表达,这种表达在转化后持续。预测FAT1在正常造血过程中的作用。我们通过使用Vav-iCre菌株构建条件敲除(cKO)小鼠来探索这一概念,其中Fat1表达在造血干细胞阶段被删除。使用多面板流式细胞术对前体和成熟血液群体进行的广泛分析显示,Fat1cKO小鼠与正常同窝动物之间没有表面上的差异。涉及集落形成单位和竞争性骨髓移植测定的进一步功能比较支持以下结论:Fat1对于正常的鼠造血作用是不必要的。
    Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.
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  • 文章类型: Case Reports
    背景:急性早幼粒细胞白血病(APL)的遗传特征是由t(15;17)(q24;q21)染色体易位导致的早幼粒细胞白血病基因(PML)与视黄酸受体α(RARα)融合。APL中罕见但反复出现的发现是衍生染色体17的同工染色体的形成;ider(17)(q10)t(15;17)或ider(17q)。APL中的这种重排导致PML-RARα融合基因的额外拷贝以及17p/TP53的丢失。由于艾德(17q)的罕见出现,这一遗传发现对预后的影响尚不清楚.病例介绍:在这里,我们描述了在马里兰大学和约翰·霍普金斯大学接受治疗的5例(17q)APL患者的临床特征和结果。
    结论:在我们的系列中,伴有ider(17q)的APL患者的预后并不差.
    BACKGROUND: Acute promyelocytic leukemia (APL) is genetically characterized by the fusion of promyelocytic leukemia (PML) gene with retinoic acid receptor alpha (RARα) resulting from a t(15;17)(q24;q21) chromosomal translocation. An infrequent but recurrent finding in APL is the formation of an isochromosome of the derivative chromosome 17; ider(17)(q10)t(15;17) or ider(17q). This rearrangement in APL results in an additional copy of the PML-RARα fusion gene as well as loss of 17p/TP53. Due to the infrequent occurrence of the ider(17q), the prognostic impact of this genetic finding is not well known. Case Presentation(s): Here, we describe the clinical characteristics and outcomes of our case series of 5 patients with ider(17q) APL treated at the University of Maryland and Johns Hopkins University.
    CONCLUSIONS: In our series, patients with APL with ider(17q) did not have a worse prognosis.
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