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  • 1.

    【2hr】Neunert CE. Management of newly diagnosed immune thrombocytopenia: can we change outcomes? Hematology Am Soc Hematol Educ Program. 2017;2017:400-405.

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    机译 Neunert CE。新诊断的免疫性血小板减少症的管理：我们可以改变结局吗？血液学Am Soc Hematol Educ Program。 2017; 2017：400-405。
    • 作者：
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2018年第1期
    摘要：
  • 2.

    【2hr】AL amyloidosis: from molecular mechanisms to targeted therapies

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    机译 AL淀粉样变性：从分子机制到靶向治疗
    • 作者：Giampaolo Merlini
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Systemic amyloidosis is caused by misfolding and extracellular deposition of circulating proteins as amyloid fibrils, resulting in the dysfunction of vital organs. The most common systemic amyloidosis, light-chain (AL) amyloidosis, is caused by misfolded light chains produced by a small, dangerous B-cell clone. The process of amyloid formation, organ targeting, and damage is multifaceted and, after disease initiation, the complexity of the downstream pathogenic cascade increases, rendering its control a challenge. Because of the progressive nature of the disease, early diagnosis to prevent end-stage organ damage is vital. Improving awareness and systematic use of biomarkers of organ damage in screening populations at risk may improve the still unsatisfactory diagnostic process. Amyloid imaging is now emerging as an important companion of biomarkers in formulating the diagnosis and prognosis and monitoring the effects of therapy. An accurate diagnosis is the basis for appropriate therapy that is risk-adapted and response-tailored. Effective treatments targeting the clone and rapidly and profoundly reducing the amyloid light chains have produced marked improvements in overall survival, making AL amyloidosis the most successful model of all amyloidoses. New therapies targeting the amyloid deposits are now under development, together with novel agents modulating light chain aggregation and proteotoxicity. The future of AL amyloidosis treatment is combination therapy and will require an innovative collaborative model for a rapid translation from bench to bedside with the ultimate aim of achieving a cure for this complex disease.
  • 3.

    【2hr】Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation

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    机译 成人ALL的最小残留疾病：技术方面及其对正确临床解释的影响
    摘要：Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results. Time will tell whether new molecular and flow cytometric high-throughput technologies can overcome the limitations of current standard methods and eventually bring additional benefits. MRD during standard ALL chemotherapy is the strongest overall prognostic indicator and has therefore been used for refining initial treatment stratification. Moreover, MRD positivity after the maintenance phase of treatment may point to an impending relapse and thus enable salvage treatment to be initiated earlier, which could possibly improve treatment results. The prognostic relevance of pretransplantation MRD was shown by several studies, and MRD high-risk patients were shown to benefit from stem cell transplantation (SCT). Also, MRD positivity after SCT correlates with worse outcomes. In addition, MRD information is very instructive in current clinical trials that test novel agents to evaluate their treatment efficacy. Although conventional clinical risk factors lose their independent prognostic significance when combined with MRD information, recently identified genetic markers may further improve the treatment stratification in ALL.
  • 4.

    【2hr】Current management of Philadelphia chromosome positive ALL and the role of stem cell transplantation

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    机译 费城染色体阳性ALL的当前处理和干细胞移植的作用。
    • 作者：Farhad Ravandi
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia exemplifies how the addition of potent targeted agents, directed at the molecular aberrations responsible for leukemic transformation, can overcome resistance mechanisms to traditional regimens and lead to improved outcomes. The introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes not only by allowing more patients to undergo allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing our reliance on this potentially toxic strategy, particularly in the less fit population. Long-term data using chemotherapy and TKI combinations demonstrate that a proportion of patients treated can achieve durable relapse-free survival without undergoing alloHCT. Furthermore, the availability of sensitive minimal residual disease monitoring assays may allow early detection of the patients who are more likely to relapse and who are likely candidates for early alloHCT. The emergence of more potent TKIs with significant activity against resistant mutations has allowed deintensification of chemotherapy regimens. Available data indicate that complete reliance on TKIs, alone or with minimal additional therapy, and elimination of more intensive chemotherapy or alloHCT is unlikely to achieve long term cure in most patients. However, introduction of other highly effective agents that can be combined with TKIs may allow further minimization of chemotherapy and alloHCT in the future, as we have witnessed in acute promyelocytic leukemia.
  • 5.

    【2hr】Progress in adult ALL: incorporation of new agents to frontline treatment

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    机译 成人ALL的进展：将新药纳入一线治疗
    摘要：Treatment of acute lymphoblastic leukemia (ALL) in adults remains a challenge, as the delivery of intensive chemotherapeutic regimens in this population is less feasible than it is in the pediatric population. This has led to higher rates of treatment-related toxicity as well as lower overall survival in the adult population. Over the past several years, a host of novel therapies (eg, immunotherapy and targeted therapies) with better tolerability than traditional chemotherapy are now being introduced into the relapsed/refractory population with very encouraging results. Additionally, insights into how to choose effective therapies for patients while minimizing drug toxicity through pharmacogenomics and the use of minimal residual disease (MRD) monitoring to escalate/de-escalate therapy have enhanced our ability to reduce treatment-related toxicity. This has led to the design of a number of clinical trials which incorporate both novel therapeutics as well as MRD-directed treatment pathways into the frontline setting. The use of increasingly personalized treatment strategies for specific disease subsets combined with standardized and rapid molecular diagnostic testing in the initial diagnosis and frontline treatment of ALL will hopefully lead to further improvements in survival for our adult patients.
  • 6.

    【2hr】Classification and risk assessment in AML: integrating cytogenetics and molecular profiling

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    机译 AML的分类和风险评估：整合细胞遗传学和分子谱分析
    摘要：In recent years, the composite molecular architecture in acute myeloid leukemia (AML) has been mapped out. We now have a clearer understanding of the key genetic determinants, the major genetic interactions, and the broad order in which these mutations occur. The next impending challenge is to discern how these recent genomic discoveries define disease biology as well as how to use molecular markers to deliver patient-tailored clinical decision support.
  • 7.

    【2hr】How and when to decide between epigenetic therapy and chemotherapy in patients with AML

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    机译 如何以及何时在AML患者中决定表观遗传疗法和化学疗法之间
    摘要：Remission induction with chemotherapy has long been the frontline treatment of acute myeloid leukemia (AML). However, intensive therapy is limited in frail patients by its associated toxicity and higher rates of failure or relapse in patients with chemoresistant disease, such as secondary AML or poor-risk cytogenetics. Frailty and chemoresistance are more frequent in older adults with AML. In recent years, epigenetic therapies with the hypomethylating agents decitabine and azacitidine have been thoroughly explored in AML. The results of two pivotal studies carried out with these agents in older adults with newly diagnosed AML have challenged the role of intensive chemotherapy as the frontline treatment option in this high-risk population. Here, we review the results of treatment with intensive chemotherapy and hypomethylating agents in older patients with AML; discuss the patient- and disease-specific criteria to integrate into treatment decision making; and also, highlight the methodological limitations of cross-study comparison in this population.
  • 8.

    【2hr】The role of targeted therapy in the management of patients with AML

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    机译 靶向治疗在AML患者管理中的作用
    • 作者：Alexander E. Perl
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration’s approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment.
  • 9.

    【2hr】Clinical implications of somatic mutations in aplastic anemia and myelodysplastic syndrome in genomic age

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    机译 基因组年龄再生障碍性贫血和骨髓增生异常综合症的体细胞突变的临床意义
    摘要：Recent technological advances in genomics have led to the discovery of new somatic mutations and have brought deeper insights into clonal diversity. This discovery has changed not only the understanding of disease mechanisms but also the diagnostics and clinical management of bone marrow failure. The clinical applications of genomics include enhancement of current prognostic schemas, prediction of sensitivity or refractoriness to treatments, and conceptualization and selective application of targeted therapies. However, beyond these traditional clinical aspects, complex hierarchical clonal architecture has been uncovered and linked to the current concepts of leukemogenesis and stem cell biology. Detection of clonal mutations, otherwise typical of myelodysplastic syndrome, in the course of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria has led to new pathogenic concepts in these conditions and created a new link between AA and its clonal complications, such as post-AA and paroxysmal nocturnal hemoglobinuria. Distinctions among founder vs subclonal mutations, types of clonal evolution (linear or branching), and biological features of individual mutations (sweeping, persistent, or vanishing) will allow for better predictions of the biologic impact they impart in individual cases. As clonal markers, mutations can be used for monitoring clonal dynamics of the stem cell compartment during physiologic aging, disease processes, and leukemic evolution.
  • 10.

    【2hr】Aging, hematopoiesis, and the myelodysplastic syndromes

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    机译 衰老，造血和骨髓增生异常综合症
    摘要：The aging hematopoietic system undergoes numerous changes, including reduced production of red blood cells and lymphocytes as well as a relative increase in the production of myeloid cells. Emerging evidence indicates that many of these changes are due to selection pressures from cell-intrinsic and cell-extrinsic factors that result in clonal shifts in the hematopoietic stem cell (HSC) pool, resulting in predominant HSC clones that exhibit the functional characteristics associated with HSC aging. Given the recent descriptions of clonal hematopoiesis in aged populations, the increased risk of developing hematologic malignancies in individuals with clonal hematopoiesis, and the many similarities in hematopoietic aging and acquired bone marrow failure (BMF) syndromes, such as myelodysplastic syndromes (MDS), this raises significant questions regarding the relationship between aging hematopoiesis and MDS, including the factors that regulate HSC aging, whether clonal hematopoiesis is required for the development of MDS, and even whether BMF is an inevitable consequence of aging. In this article, we will review our current understanding of these processes and the potential intersections among them.
  • 11.

    【2hr】Old and new tools in the clinical diagnosis of inherited bone marrow failure syndromes

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    机译 新旧遗传性骨髓衰竭综合征临床诊断工具
    摘要：Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other physical features that are often recognizable early in life. However, increasing application of genomic sequencing and clinical awareness of subtle disease presentations have led to the recognition of IBMFS in pediatric and adult populations more frequently than previously realized, such as those with early onset myelodysplastic syndrome (MDS). Given the well-defined differences in clinical management needs and outcomes for aplastic anemia, acute myeloid leukemia, and MDS in patients with an IBMFS vs those occurring sporadically, as well as nonhematologic comorbidities in patients with IBMFSs, it is critical for hematologists to understand how to approach screening for the currently known IBMFSs. This review presents a practical approach for the clinical hematologist that outlines when to suspect an IBMFS and how to use various diagnostic tools, from physical examination to screening laboratory tests and genomics, for the diagnosis of the most frequent IBMFSs: Fanconi anemia, telomere biology disorders, Diamond-Blackfan anemia, GATA2 deficiency syndrome, Shwachman-Diamond syndrome, and severe congenital neutropenia.
  • 12.

    【2hr】Inherited bone marrow failure syndromes: considerations pre- and posttransplant

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    机译 遗传性骨髓衰竭综合征：移植前后的注意事项
    • 作者：Blanche P. Alter
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Patients with inherited bone marrow failure syndromes are usually identified when they develop hematologic complications such as severe bone marrow failure, myelodysplastic syndrome, or acute myeloid leukemia. They often have specific birth defects or other physical abnormalities that suggest a syndrome, and sequencing of specific genes or next-generation sequencing can determine or confirm the particular syndrome. The 4 most frequent syndromes are Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond syndrome. This review discusses the major complications that develop as the patients with these syndromes age, as well as additional late effects following hematopoietic stem cell transplantation. The most common complications are iron overload in transfused patients and syndrome-specific malignancies in untransplanted patients, which may occur earlier and with higher risks in those who have received transplants.
  • 13.

    【2hr】Treatment of inherited bone marrow failure syndromes beyond transplantation

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    机译 移植后遗传性骨髓衰竭综合征的治疗
    摘要：Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.
  • 14.

    【2hr】Treatment-free remission in CML: who, how, and why?

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    机译 CML中的无治疗缓解：谁，如何以及为什么？
    • 作者：Francois-Xavier Mahon
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Chronic myeloid leukemia (CML) is the best example of successful targeted therapy. Today, the overall survival of patients with CML treated by using tyrosine kinase inhibitors (TKIs) is very close to that of the healthy population. The current question is: how can we further ameliorate the clinical outcome of patients with CML? Clinical trials have shown that some patients with CML in the chronic phase who achieve sustained deep molecular responses on TKI therapy can safely suspend therapy with no evidence of relapse. The long follow-up studies and the number of eligible patients have now validated the concept of treatment-free remission (ie, the ability to maintain a molecular response after stopping therapy). It should be considered as the future criterion to evaluate the success of clinical trials, especially if we want to take into account the quality of life of patients in addition to the economic aspect. Because post-TKI discontinuation follow-ups have been increasing over time with no evidence of relapse in some patients, the next step for the coming decade will be to address the topic of CML cure.
  • 15.

    【2hr】Cardiovascular care of patients with chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) therapy

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    机译 酪氨酸激酶抑制剂（TKI）治疗对慢性粒细胞白血病（CML）患者的心血管保健
    摘要：Cardiovascular (CV) health has emerged as an important consideration in patients with chronic myeloid leukemia (CML) because of improved prognosis. Indeed, the success of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has increased the focus on survivorship and late toxicity in oncological care. Survivorship issues in this population include CV disease prevention, given its prevalence in the general population. The introduction of BCR-ABL1 TKIs represented a unique concept of indefinite cancer therapy, only recently evolving to include “treatment-free remission.” Importantly, later-generation BCR-ABL1 TKIs have been associated with CV complications. Dasatinib has been associated with pleural/pericardial effusions and pulmonary hypertension, whereas nilotinib and ponatinib have been linked to the development of vascular occlusive events. There is currently a dearth of data with respect to the mechanisms of drug toxicities, the subsets of patients at risk, and prevention and treatment strategies to mitigate CV complications in patients with CML. Nevertheless, optimal patient CV risk assessment needs to become a more central tenet of patient care in CML. We propose several practical considerations for the practicing oncologist relative to the CV health of patients with CML, especially those on chronic TKI therapy.
  • 16.

    【2hr】Novel approaches to therapy in CML

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    机译 CML治疗的新方法
    • 作者：Ravi Bhatia
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Treatment with tyrosine kinase inhibitors (TKIs) results in remission and prolongation of survival in most chronic myeloid leukemia (CML) patients but fails to eliminate the leukemia stem cells (LSCs) responsible for disease development and propagation. This accounts for the clinical observation that TKI discontinuation leads to rapid leukemia relapse. Most patients require continued treatment to prevent relapse, with associated risk of relapse, toxicity, teratogenic effects, financial burden, and noncompliance. Understanding LSC resistance to TKI and development of strategies to increase the proportion of CML patients achieving treatment-free remissions is a critical area of investigation in CML. In addition, LSCs are the source of TKI resistance, relapse, or disease progression, which is another major area of need in CML treatment. It is now understood that BCR-ABL kinase-independent mechanisms are responsible for retention of LSC subpopulations. It is likely that both cell-intrinsic and microenvironmental mechanisms contribute to LSC maintenance. Here, we review the current understanding of mechanisms underlying persistence of CML LSCs during TKI treatment, recently described approaches to target these cells and emerging clinical trials, and the challenges impeding more rapid progress in achieving cures for a greater number of CML patients.
  • 17.

    【2hr】Incidental venous thromboembolism: is anticoagulation indicated?

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    机译 偶发性静脉血栓栓塞：是否建议抗凝治疗？
    摘要：Patients with cancer have a high risk of venous thromboembolism (VTE) and about one-half of these events are incidentally detected. The prognosis of incidental VTE appears to be similar to symptomatic events, with comparably high rates of recurrent VTE in this patient population. In the absence of major contraindications, anticoagulant treatment with low-molecular-weight heparin for 3 to 6 months is generally recommended for incidental proximal deep vein thrombosis as well as for incidental pulmonary embolism that involves multiple subsegmental or more proximal pulmonary arteries. The decision of whether to extend treatment beyond 3 to 6 months should be evaluated on a case-by-case basis after periodic reassessment of the risks factors for bleeding and recurrent VTE while also taking into account patient preferences. The clinical relevance of a single incidental subsegmental pulmonary embolism without concomitant deep vein thrombosis is uncertain and either a watchful approach or a shorter course of anticoagulation to minimize the bleeding risk may also be considered. Preliminary evidence suggests that anticoagulation treatment may be beneficial for cancer patients with incidental distal deep vein thrombosis or incidental splanchnic vein thrombosis.
  • 18.

    【2hr】When can we stop anticoagulation in patients with cancer-associated thrombosis?

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    机译 癌症相关血栓形成的患者何时可以停止抗凝治疗？
    • 作者：Agnes Y. Y. Lee
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：The optimal duration of anticoagulant therapy in patients with cancer-associated venous thromboembolism (VTE) is unknown. Without well-designed studies evaluating the efficacy, safety, and cost-effectiveness of continuing anticoagulant therapy beyond the acute treatment period of 3 to 6 months, evidence-based recommendations are lacking. Consensus guidelines generally suggest continuing anticoagulation treatment in patients with active cancer or receiving cancer treatment, with periodic reassessment of the risks and benefits. Unfortunately, with very little published data on the epidemiology of cancer-associated VTE beyond the initial 6 months, it is not possible for clinicians and patients to weigh risks and benefits in a quantitatively informed manner. Further research is needed to provide reliable and contemporary estimates on the risk of recurrent VTE off anticoagulant therapy, risk of bleeding on anticoagulant therapy, case fatality or all-cause mortality, and other important consequences of living with cancer-associated VTE. This chapter provides an overview of the published literature on real-world data on anticoagulant therapy use, the risks and risk factors of recurrent VTE and bleeding, and patient preference and values regarding long-term anticoagulation treatment. It will conclude with a pragmatic, experience-informed approach for tailoring anticoagulant therapy in patients with cancer-associated VTE.
  • 19.

    【2hr】Direct oral anticoagulants: now also for prevention and treatment of cancer-associated venous thromboembolism?

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    机译 直接口服抗凝剂：现在还用于预防和治疗癌症相关的静脉血栓栓塞吗？
    摘要：Data on specific studies in cancer patients using direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE) are still scarce. For preventing VTE with DOACs, current experience is still very limited, so definite conclusions cannot yet be drawn. However, DOACs have so far been compared with vitamin K antagonists (VKAs) in patients with acute VTE in 5 studies, and several hundreds of patients included in these studies had either active cancer, a history of cancer, or a new occurrence of cancer during the course of disease. Meta-analyses have revealed an at least similar efficacy and safety profile of DOACs compared with VKAs. A number of studies of cancer patients investigating primary prevention and treatment are underway, and some will be finalized soon. Nevertheless, we might need further trials, specifically on the prevention of VTE in patients who are at particularly high risk. This article also includes a personal opinion on the use of DOACs in cancer patients. In conclusion, the currently available data show that DOACs might be safe and efficacious in the treatment of VTE, however, this has yet to be proven in specifically designed trials in patients with cancer. With regard to prevention, thus far, even less data exist, and the outcomes of the ongoing studies have to be evaluated before DOACs may be used for primary prevention.
  • 20.

    【2hr】Thrombocytopenia in pregnancy

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    机译 孕妇血小板减少
    摘要：Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy. Recent trends in the management of immune thrombocytopenia translate into more women contemplating pregnancy while on treatment with thrombopoietin receptor agonists, rituximab, or mycophenylate, which pose known or unknown risks to the fetus. New criteria to diagnose preeclampsia, judicious reliance on measurement of ADAMTS13 to make management decisions in suspected thrombotic thrombocytopenic purpura, new evidence supporting the efficacy and safety of anticomplement therapy for atypical hemolytic uremic syndrome during pregnancy, and implications of thrombotic microangiopathies for subsequent pregnancies are evolving rapidly. The goals of the chapter are to help the hematology consultant work through the differential diagnosis of thrombocytopenia in pregnancy based on trimester of presentation, severity of thrombocytopenia, and coincident clinical and laboratory manifestations, and to provide guidance for dealing with some of the more common and difficult diagnostic and management decisions.
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