Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101227
Marianela Iriarte-Gahete , Laura Tarancon-Diez , Vanesa Garrido-Rodríguez , Manuel Leal , Yolanda María Pacheco
Iron is essential for numerous physiological processes and its deficiency often leads to anemia. Iron deficiency (ID) is a global problem, primarily affecting reproductive-age women and children, especially in developing countries. Diagnosis uses classical biomarkers like ferritin or transferrin saturation. Recent advancements include using soluble transferrin receptor (sTfR) or hepcidin for improved detection and classification of absolute and functional iron deficiencies, though mostly used in research. ID without anemia may present symptoms like asthenia and fatigue, even without relevant clinical consequences. ID impacts not only red-blood cells but also immune system cells, highlighting its importance in global health and immune-related comorbidities. Managing ID, requires addressing its cause and selecting appropriate iron supplementation. Various improved oral and intravenous products are available, but further research is needed to refine treatment strategies. This review updates on absolute and functional iron deficiencies, their relationships with the immune system and advancements in diagnosis and therapies.
铁是多种生理过程的必需元素，缺铁往往会导致贫血。缺铁（ID）是一个全球性问题，主要影响育龄妇女和儿童，尤其是在发展中国家。诊断使用传统的生物标志物，如铁蛋白或转铁蛋白饱和度。最近的进展包括使用可溶性转铁蛋白受体（sTfR）或血钙素来改进绝对性和功能性铁缺乏症的检测和分类，但主要用于研究。没有贫血的 ID 可能会出现气喘和疲劳等症状，甚至没有相关的临床后果。ID 不仅会影响红血细胞，还会影响免疫系统细胞，这凸显了它在全球健康和免疫相关合并症中的重要性。治疗 ID 需要解决其病因并选择适当的铁质补充剂。目前已有各种改良的口服和静脉注射产品，但还需要进一步的研究来完善治疗策略。本综述将介绍绝对性和功能性铁缺乏症的最新情况、它们与免疫系统的关系以及诊断和治疗方面的进展。
{"title":"Absolute and functional iron deficiency: Biomarkers, impact on immune system, and therapy","authors":"Marianela Iriarte-Gahete , Laura Tarancon-Diez , Vanesa Garrido-Rodríguez , Manuel Leal , Yolanda María Pacheco","doi":"10.1016/j.blre.2024.101227","DOIUrl":"10.1016/j.blre.2024.101227","url":null,"abstract":"<div><div>Iron is essential for numerous physiological processes and its deficiency often leads to anemia. Iron deficiency (ID) is a global problem, primarily affecting reproductive-age women and children, especially in developing countries. Diagnosis uses classical biomarkers like ferritin or transferrin saturation. Recent advancements include using soluble transferrin receptor (sTfR) or hepcidin for improved detection and classification of absolute and functional iron deficiencies, though mostly used in research. ID without anemia may present symptoms like asthenia and fatigue, even without relevant clinical consequences. ID impacts not only red-blood cells but also immune system cells, highlighting its importance in global health and immune-related comorbidities. Managing ID, requires addressing its cause and selecting appropriate iron supplementation. Various improved oral and intravenous products are available, but further research is needed to refine treatment strategies. This review updates on absolute and functional iron deficiencies, their relationships with the immune system and advancements in diagnosis and therapies.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101227"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101224
Lacey S. Williams , Teja Nagaradona , Prathik Nalamalapu , Catherine Lai
Acute myeloid leukemia (AML) is a disease primarily affecting older adults. However, not all patients at older ages are suitable for curative treatment with intensive chemotherapy due to “frailty” demonstrated by their functional status, physiologic reserve, and vulnerability to disease and treatment morbidity. Lack of consensus exists on how to select older, less fit patients most appropriate for standard intensive chemotherapy (IC), hypomethylating agents (HMA) with venetoclax, or less intensive regimens. A total of 37 studies of frailty assessments and composite indices in AML show heterogeneous results regarding the ability of frailty and Comprehensive Geriatric Assessment (CGA) measures to predict treatment outcomes. CGA, Geriatric 8 (G8) risk score, and hematopoietic cell transplant comorbidity index (HCT-CI) show association with prognosis, and should be validated in larger therapeutic trials. Studies of biomarkers, like albumin and C-reactive protein, and patient-reported outcomes demonstrate the potential to enhance information gained from rigorous geriatric assessment.
急性髓性白血病（AML）是一种主要影响老年人的疾病。然而，并非所有老年患者都适合接受强化化疗的根治性治疗，这是因为他们的 "虚弱 "表现在其功能状态、生理储备以及对疾病和治疗发病率的脆弱性。对于如何选择最适合接受标准强化化疗（IC）、低甲基化药物（HMA）与 Venetoclax 或较低强化方案的老年体弱患者，目前尚无共识。共有 37 项关于急性髓细胞白血病患者虚弱程度评估和综合指数的研究显示，虚弱程度和老年综合评估（CGA）指标预测治疗结果的能力存在差异。CGA、老年8（G8）风险评分和造血细胞移植综合指数（HCT-CI）显示与预后有关，应在更大规模的治疗试验中加以验证。对白蛋白和 C 反应蛋白等生物标志物以及患者报告结果的研究表明，通过严格的老年病学评估所获得的信息有可能得到加强。
{"title":"Breaking down frailty: Assessing vulnerability in acute myeloid leukemia","authors":"Lacey S. Williams , Teja Nagaradona , Prathik Nalamalapu , Catherine Lai","doi":"10.1016/j.blre.2024.101224","DOIUrl":"10.1016/j.blre.2024.101224","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a disease primarily affecting older adults. However, not all patients at older ages are suitable for curative treatment with intensive chemotherapy due to “frailty” demonstrated by their functional status, physiologic reserve, and vulnerability to disease and treatment morbidity. Lack of consensus exists on how to select older, less fit patients most appropriate for standard intensive chemotherapy (IC), hypomethylating agents (HMA) with venetoclax, or less intensive regimens. A total of 37 studies of frailty assessments and composite indices in AML show heterogeneous results regarding the ability of frailty and Comprehensive Geriatric Assessment (CGA) measures to predict treatment outcomes. CGA, Geriatric 8 (G8) risk score, and hematopoietic cell transplant comorbidity index (HCT-CI) show association with prognosis, and should be validated in larger therapeutic trials. Studies of biomarkers, like albumin and C-reactive protein, and patient-reported outcomes demonstrate the potential to enhance information gained from rigorous geriatric assessment.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101224"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101226
Qiujin Shen , Xiaowen Gong , Yahui Feng , Yu Hu , Tiantian Wang , Wen Yan , Wei Zhang , Saibing Qi , Robert Peter Gale , Junren Chen
Measurable residual disease (MRD)-testing is used in many haematological cancers to estimate relapse risk and to direct therapy. Sometimes MRD-test results are used for regulatory approval. However, some people including regulators wrongfully believe results of MRD-testing are highly accurate and of proven efficacy in directing therapy. We review MRD-testing technologies and evaluate the accuracy of MRD-testing for predicting relapse and the strength of evidence supporting efficacy of MRD-guided therapy. We show that at the individual level MRD-test results are often an inaccurate relapse predictor. Also, no convincing data indicate that increasing therapy-intensity based on a positive MRD-test reduces relapse risk or improves survival. We caution against adjusting therapy-intensity based solely on results of MRD-testing.
{"title":"Measurable residual disease (MRD)-testing in haematological cancers: A giant leap forward or sideways?","authors":"Qiujin Shen , Xiaowen Gong , Yahui Feng , Yu Hu , Tiantian Wang , Wen Yan , Wei Zhang , Saibing Qi , Robert Peter Gale , Junren Chen","doi":"10.1016/j.blre.2024.101226","DOIUrl":"10.1016/j.blre.2024.101226","url":null,"abstract":"<div><div>Measurable residual disease (MRD)-testing is used in many haematological cancers to estimate relapse risk and to direct therapy. Sometimes MRD-test results are used for regulatory approval. However, some people including regulators wrongfully believe results of MRD-testing are highly accurate and of proven efficacy in directing therapy. We review MRD-testing technologies and evaluate the accuracy of MRD-testing for predicting relapse and the strength of evidence supporting efficacy of MRD-guided therapy. We show that at the individual level MRD-test results are often an inaccurate relapse predictor. Also, no convincing data indicate that increasing therapy-intensity based on a positive MRD-test reduces relapse risk or improves survival. We caution against adjusting therapy-intensity based solely on results of MRD-testing.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101226"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101240
Jean Escal , Geraldine Poenou , Xavier Delavenne , Souad Bezzeghoud , Valentine Mismetti , Marc Humbert , David Montani , Laurent Bertoletti
The use of oral anticoagulants in the management of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) presents distinct therapeutic challenges and benefits. In PAH, the benefits of oral anticoagulation are uncertain, with studies yielding mixed results on their efficacy and safety. Conversely, oral anticoagulants are a cornerstone in the treatment of CTEPH, where their use is consistently recommended to prevent recurrent thromboembolic events. The choice between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) remains a significant clinical question, as each type presents advantages and potential drawbacks. Furthermore, drug-drug interactions (DDIs) with concomitant PAH and CTEPH treatments complicate anticoagulant management, necessitating careful consideration of individual patient regimens. This review examines the current evidence on oral anticoagulant use in PAH and CTEPH and discusses the implications of DDIs within a context of multi-drug treatments, including targeted drugs in PAH.
{"title":"Tailoring oral anticoagulant treatment in the era of multi-drug therapies for PAH and CTEPH","authors":"Jean Escal , Geraldine Poenou , Xavier Delavenne , Souad Bezzeghoud , Valentine Mismetti , Marc Humbert , David Montani , Laurent Bertoletti","doi":"10.1016/j.blre.2024.101240","DOIUrl":"10.1016/j.blre.2024.101240","url":null,"abstract":"<div><div>The use of oral anticoagulants in the management of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) presents distinct therapeutic challenges and benefits. In PAH, the benefits of oral anticoagulation are uncertain, with studies yielding mixed results on their efficacy and safety. Conversely, oral anticoagulants are a cornerstone in the treatment of CTEPH, where their use is consistently recommended to prevent recurrent thromboembolic events. The choice between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) remains a significant clinical question, as each type presents advantages and potential drawbacks. Furthermore, drug-drug interactions (DDIs) with concomitant PAH and CTEPH treatments complicate anticoagulant management, necessitating careful consideration of individual patient regimens. This review examines the current evidence on oral anticoagulant use in PAH and CTEPH and discusses the implications of DDIs within a context of multi-drug treatments, including targeted drugs in PAH.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101240"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101237
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Liquid biopsy, particularly circulating tumor DNA (ctDNA), has drawn a lot of attention as a non- or minimal-invasive detection approach for clinical applications in patients with cancer. Many hematological malignancies are well suited for serial and repeated ctDNA surveillance due to relatively high ctDNA concentrations and high loads of tumor-specific genetic and epigenetic abnormalities. Progress of detecting technology in recent years has improved sensitivity and specificity significantly, thus broadening and strengthening the potential utilities of ctDNA including early diagnosis, prognosis estimation, treatment response evaluation, minimal residual disease monitoring, targeted therapy selection, and immunotherapy surveillance. This manuscript reviews the detection methodologies, clinical application and future challenges of ctDNA in hematological malignancies, especially for lymphomas, myeloma and leukemias.
液体活检，尤其是循环肿瘤 DNA (ctDNA)，作为一种无创或微创的检测方法，在癌症患者的临床应用中备受关注。由于ctDNA浓度相对较高，且肿瘤特异性基因和表观遗传学异常负荷较高，许多血液恶性肿瘤非常适合连续和重复ctDNA监测。近年来检测技术的进步大大提高了灵敏度和特异性，从而扩大和加强了ctDNA的潜在用途，包括早期诊断、预后评估、治疗反应评估、最小残留病监测、靶向治疗选择和免疫治疗监测。本手稿回顾了ctDNA在血液恶性肿瘤，尤其是淋巴瘤、骨髓瘤和白血病中的检测方法、临床应用和未来挑战。
{"title":"Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future","authors":"Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun","doi":"10.1016/j.blre.2024.101237","DOIUrl":"10.1016/j.blre.2024.101237","url":null,"abstract":"<div><div>Liquid biopsy, particularly circulating tumor DNA (ctDNA), has drawn a lot of attention as a non- or minimal-invasive detection approach for clinical applications in patients with cancer. Many hematological malignancies are well suited for serial and repeated ctDNA surveillance due to relatively high ctDNA concentrations and high loads of tumor-specific genetic and epigenetic abnormalities. Progress of detecting technology in recent years has improved sensitivity and specificity significantly, thus broadening and strengthening the potential utilities of ctDNA including early diagnosis, prognosis estimation, treatment response evaluation, minimal residual disease monitoring, targeted therapy selection, and immunotherapy surveillance. This manuscript reviews the detection methodologies, clinical application and future challenges of ctDNA in hematological malignancies, especially for lymphomas, myeloma and leukemias.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101237"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101225
Alex Hoover , Lucie M. Turcotte , Rachel Phelan , Crystal Barbus , Arpana Rayannavar , Bradley S. Miller , Erin E. Reardon , Nicole Theis-Mahon , Margaret L. MacMillan
Fanconi anemia (FA) is a rare and complex inherited genetic disorder characterized by impaired DNA repair mechanisms leading to genomic instability. Individuals with FA have increased susceptibility to congenital anomalies, progressive bone marrow failure, leukemia and malignant tumors, endocrinopathies and other medical issues. In recent decades, steadily improved approaches to hematopoietic cell transplantation (HCT), the only proven curative therapy for the hematologic manifestations of FA, have significantly increased the life expectancy of affected individuals, illuminating the need to understand the long-term consequences and multi-organ ramifications. Utilizing a systematized review approach with narrative synthesis of each primary issue and organ system, we shed light on the challenges and opportunities for optimizing the care and quality of life for individuals with FA and identify knowledge gaps informing future research directions.
范可尼贫血症（Fanconi anemia，FA）是一种罕见的复杂遗传性疾病，其特点是 DNA 修复机制受损，导致基因组不稳定。范可尼贫血症患者易患先天性畸形、进行性骨髓衰竭、白血病和恶性肿瘤、内分泌疾病和其他疾病。近几十年来，造血细胞移植（HCT）方法不断改进，这是治疗 FA 血液学表现的唯一行之有效的疗法，大大延长了患者的预期寿命，这说明我们有必要了解其长期后果和多器官影响。我们采用系统化的综述方法，对每个主要问题和器官系统进行叙述性综合，揭示了优化 FA 患者护理和生活质量所面临的挑战和机遇，并确定了未来研究方向的知识缺口。
{"title":"Longitudinal clinical manifestations of Fanconi anemia: A systematized review","authors":"Alex Hoover , Lucie M. Turcotte , Rachel Phelan , Crystal Barbus , Arpana Rayannavar , Bradley S. Miller , Erin E. Reardon , Nicole Theis-Mahon , Margaret L. MacMillan","doi":"10.1016/j.blre.2024.101225","DOIUrl":"10.1016/j.blre.2024.101225","url":null,"abstract":"<div><div>Fanconi anemia (FA) is a rare and complex inherited genetic disorder characterized by impaired DNA repair mechanisms leading to genomic instability. Individuals with FA have increased susceptibility to congenital anomalies, progressive bone marrow failure, leukemia and malignant tumors, endocrinopathies and other medical issues. In recent decades, steadily improved approaches to hematopoietic cell transplantation (HCT), the only proven curative therapy for the hematologic manifestations of FA, have significantly increased the life expectancy of affected individuals, illuminating the need to understand the long-term consequences and multi-organ ramifications. Utilizing a systematized review approach with narrative synthesis of each primary issue and organ system, we shed light on the challenges and opportunities for optimizing the care and quality of life for individuals with FA and identify knowledge gaps informing future research directions.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101225"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101239
Qiujin Shen , Xiaowen Gong , Yahui Feng , Yu Hu , Tiantian Wang , Wen Yan , Wei Zhang , Saibing Qi , Robert Peter Gale , Junren Chen
{"title":"Corrigendum to “Measurable residual disease (MRD)-testing in haematological cancers: A giant leap forward or sideways?”[BLOOD REVIEWS, 9 August 2024, https://doi.org/10.1016/j.blre.2024.101226]","authors":"Qiujin Shen , Xiaowen Gong , Yahui Feng , Yu Hu , Tiantian Wang , Wen Yan , Wei Zhang , Saibing Qi , Robert Peter Gale , Junren Chen","doi":"10.1016/j.blre.2024.101239","DOIUrl":"10.1016/j.blre.2024.101239","url":null,"abstract":"","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101239"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101242
Gil Hevroni , Mounika Vattigunta , Dickran Kazandjian , David Coffey , Benjamin Diamond , Francesco Maura , James Hoffman , Ola Landgren
In the 1960s, through laboratory-based investigations of peripheral blood partnered with detailed clinical annotations, Dr. Waldenström described a condition he called “benign monoclonal gammopathy”. These patients were asymptomatic with a detectable monoclonal protein, and did not meet imaging and laboratory criteria for multiple myeloma. In 1978, through observational retrospective review of medical records, Dr. Kyle observed that not all cases of monoclonal gammopathy were benign. He introduced the term monoclonal gammopathy of undetermined significance (MGUS) to describe a condition that may potentially progress to multiple myeloma (MM), highlighting clinical inability in predicting which patients might progress. In 1980, Drs. Kyle and Greipp described 6 cases which did not fit the definitions of MGUS or MM, and they remained asymptomatic after at least 5 years of follow-up; they were proposed to have smoldering multiple myeloma (SMM). Over time, SMM was defined by arbitrary numerical values (≥10 % plasma cells in the bone marrow and serum M-protein concentration ≥ 3 g/dL). Numerous clinical scores have been developed to define high-risk groups for progression to MM. Current statistical models for progression provide only average risk scores, offering limited clinical utility since the risk of progression at an individual level remains unknown. Physician-scientists are focusing on emerging technologies, such as whole genome sequencing, tumor microenvironment analysis, and single-cell RNA sequencing, to understand precursor states at a molecular level. The overarching goal of these technologies is to better characterize monoclonal gammopathy and other myeloma precursor states. This will enable clinicians to provide more precise, individualized risk assessments and ultimately improve patient outcomes. This review outlines the history of MM precursor states, current definitions, challenges in risk stratification models, and the role of emerging technologies in enhancing predictions and outcomes.
20 世纪 60 年代，通过对伴有详细临床注释的外周血进行实验室检查，瓦尔登斯特伦博士描述了一种他称之为 "良性单克隆性腺病 "的病症。这些患者没有症状，但可检测到单克隆蛋白，而且不符合多发性骨髓瘤的影像学和实验室标准。1978 年，凯尔博士通过对医疗记录的观察和回顾，发现并非所有的单克隆丙种球蛋白病都是良性的。他提出了 "意义未定的单克隆丙种球蛋白病"（MGUS）一词，用来描述一种有可能发展为多发性骨髓瘤（MM）的病症，强调临床上无法预测哪些患者可能会发展为多发性骨髓瘤。1980 年，Kyle 和 Greipp 医生描述了 6 例不符合 MGUS 或 MM 定义的病例，这些病例在随访至少 5 年后仍无症状；他们被认为患有烟雾型多发性骨髓瘤（SMM）。随着时间的推移，SMM 被任意用数值来定义（骨髓中浆细胞≥10%，血清 M 蛋白浓度≥3 g/dL）。目前已开发出许多临床评分方法，用于定义进展为 MM 的高危人群。目前的进展统计模型仅提供平均风险评分，临床实用性有限，因为个体水平的进展风险仍然未知。医生科学家们正在关注新兴技术，如全基因组测序、肿瘤微环境分析和单细胞 RNA 测序，以了解分子水平的前体状态。这些技术的总体目标是更好地描述单克隆丙种球蛋白病和其他骨髓瘤前体状态。这将使临床医生能够提供更精确、更个性化的风险评估，并最终改善患者的预后。本综述概述了骨髓瘤前体状态的历史、当前的定义、风险分层模型面临的挑战以及新兴技术在提高预测和预后方面的作用。
{"title":"From MGUS to multiple myeloma: Unraveling the unknown of precursor states","authors":"Gil Hevroni , Mounika Vattigunta , Dickran Kazandjian , David Coffey , Benjamin Diamond , Francesco Maura , James Hoffman , Ola Landgren","doi":"10.1016/j.blre.2024.101242","DOIUrl":"10.1016/j.blre.2024.101242","url":null,"abstract":"<div><div>In the 1960s, through laboratory-based investigations of peripheral blood partnered with detailed clinical annotations, Dr. Waldenström described a condition he called “benign monoclonal gammopathy”. These patients were asymptomatic with a detectable monoclonal protein, and did not meet imaging and laboratory criteria for multiple myeloma. In 1978, through observational retrospective review of medical records, Dr. Kyle observed that not all cases of monoclonal gammopathy were benign. He introduced the term monoclonal gammopathy of undetermined significance (MGUS) to describe a condition that may potentially progress to multiple myeloma (MM), highlighting clinical inability in predicting which patients might progress. In 1980, Drs. Kyle and Greipp described 6 cases which did not fit the definitions of MGUS or MM, and they remained asymptomatic after at least 5 years of follow-up; they were proposed to have smoldering multiple myeloma (SMM). Over time, SMM was defined by arbitrary numerical values (≥10 % plasma cells in the bone marrow and serum M-protein concentration ≥ 3 g/dL). Numerous clinical scores have been developed to define high-risk groups for progression to MM. Current statistical models for progression provide only average risk scores, offering limited clinical utility since the risk of progression at an individual level remains unknown. Physician-scientists are focusing on emerging technologies, such as whole genome sequencing, tumor microenvironment analysis, and single-cell RNA sequencing, to understand precursor states at a molecular level. The overarching goal of these technologies is to better characterize monoclonal gammopathy and other myeloma precursor states. This will enable clinicians to provide more precise, individualized risk assessments and ultimately improve patient outcomes. This review outlines the history of MM precursor states, current definitions, challenges in risk stratification models, and the role of emerging technologies in enhancing predictions and outcomes.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101242"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101229
Mobil Akhmedov , J. Luis Espinoza
Patients undergoing hematopoietic cell transplantation (HCT) have an increased risk of developing severe infections. In recent years, bloodstream infections caused by Gram-negative bacteria have been increasingly reported among HCT recipients, and many of these infections are caused by bacterial strains of the Enterobacterales order. Among these pathogens, particularly concerning are the multidrug-resistant Enterobacterales (MDRE), such as Extended Spectrum β-lactamase-producing Enterobacterales and Carbapenem-resistant Enterobacterales, since infections caused by these pathogens are difficult to treat due to the limited antimicrobial options and are associated with worse transplant outcomes. We summarized the evidence from studies published in PubMed and Scopus on the burden of MDRE infections in HCT recipients, and strategies for the management and prevention of these infections, including strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship, the use of probiotics, and fecal microbiota transplantation, are also discussed.
{"title":"Addressing the surge of infections by multidrug-resistant Enterobacterales in hematopoietic cell transplantation","authors":"Mobil Akhmedov , J. Luis Espinoza","doi":"10.1016/j.blre.2024.101229","DOIUrl":"10.1016/j.blre.2024.101229","url":null,"abstract":"<div><div>Patients undergoing hematopoietic cell transplantation (HCT) have an increased risk of developing severe infections. In recent years, bloodstream infections caused by Gram-negative bacteria have been increasingly reported among HCT recipients, and many of these infections are caused by bacterial strains of the <em>Enterobacterales</em> order. Among these pathogens, particularly concerning are the multidrug-resistant <em>Enterobacterales</em> (MDRE), such as Extended Spectrum β-lactamase-producing <em>Enterobacterales</em> and Carbapenem-resistant <em>Enterobacterales</em>, since infections caused by these pathogens are difficult to treat due to the limited antimicrobial options and are associated with worse transplant outcomes. We summarized the evidence from studies published in PubMed and Scopus on the burden of MDRE infections in HCT recipients, and strategies for the management and prevention of these infections, including strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship, the use of probiotics, and fecal microbiota transplantation, are also discussed.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101229"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.blre.2024.101238
Dahniel Sastow , Hannah Levavi , Nicole Wagner , Keith Pratz , Douglas Tremblay
Older/unfit adults with AML have worse outcomes and fewer treatment options than their younger/fit counterparts. In vitro studies have found a synergistic effect of hypomethylating agents (HMA) with venetoclax (VEN) on AML cells and since the phase 3 VIALE-A trial demonstrated a survival benefit, HMA + VEN has become the standard of care in the frontline setting for older/unfit adults with AML. Unfortunately, the standard 28-day cycle of VEN is associated with a high degree of myelosuppression leading to treatment delays and dose modifications. Many small retrospective studies have successfully shown comparable outcomes to VIALE-A with reduced dose/duration of VEN. Furthermore, low dose metronomic dosing of HMA + VEN has shown clinical benefit while minimizing myelotoxicity. Future trials are vital to understand the appropriate dose of VEN in combination with HMA, to evaluate HMA + VEN compared to intensive therapy for younger/fit patients, and to explore its utility in the relapsed/refractory setting.
与年轻/身体健康的患者相比，老年/身体不健康的成人急性髓细胞白血病患者的治疗效果更差，治疗方案更少。体外研究发现，低甲基化药物（HMA）与 Venetoclax（VEN）对急性髓细胞白血病细胞有协同作用，自从 VIALE-A 3 期试验显示生存获益后，HMA + VEN 已成为急性髓细胞白血病老年/非适应症成人患者的一线治疗标准。遗憾的是，标准的 28 天 VEN 周期与高度骨髓抑制有关，导致治疗延迟和剂量调整。许多小型回顾性研究成功表明，在减少 VEN 剂量/疗程的情况下，疗效与 VIALE-A 相当。此外，HMA + VEN 的低剂量节律给药已显示出临床疗效，同时将骨髓毒性降至最低。未来的试验对于了解 VEN 与 HMA 联用的适当剂量、评估 HMA + VEN 与针对年轻/适合患者的强化治疗的比较以及探索其在复发/难治性病例中的应用至关重要。
{"title":"Ven the dose matters: Venetoclax dosing in the frontline treatment of AML","authors":"Dahniel Sastow , Hannah Levavi , Nicole Wagner , Keith Pratz , Douglas Tremblay","doi":"10.1016/j.blre.2024.101238","DOIUrl":"10.1016/j.blre.2024.101238","url":null,"abstract":"<div><div>Older/unfit adults with AML have worse outcomes and fewer treatment options than their younger/fit counterparts. In vitro studies have found a synergistic effect of hypomethylating agents (HMA) with venetoclax (VEN) on AML cells and since the phase 3 VIALE-A trial demonstrated a survival benefit, HMA + VEN has become the standard of care in the frontline setting for older/unfit adults with AML. Unfortunately, the standard 28-day cycle of VEN is associated with a high degree of myelosuppression leading to treatment delays and dose modifications. Many small retrospective studies have successfully shown comparable outcomes to VIALE-A with reduced dose/duration of VEN. Furthermore, low dose metronomic dosing of HMA + VEN has shown clinical benefit while minimizing myelotoxicity. Future trials are vital to understand the appropriate dose of VEN in combination with HMA, to evaluate HMA + VEN compared to intensive therapy for younger/fit patients, and to explore its utility in the relapsed/refractory setting.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"68 ","pages":"Article 101238"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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