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  • 1.

    【2hr】Diagnosis and management of postpartum ovarian vein thrombosis

    包量

    机译 产后卵巢静脉血栓形成的诊断和处理
    摘要：Case presentation: A 26-year-old woman experienced persistent fever (39.5°C), chills, and right-lower-quadrant tenderness 3 days after caesarean delivery. A computed tomography (CT) scan of the abdomen and pelvis with contrast revealed enlargement of her right ovarian vein with an associated intraluminal filling defect. What is the best treatment of this patient?
  • 2.

    【2hr】New monogenic disorders identify more pathways to neutropenia: from the clinic to next-generation sequencing

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    机译 新的单基因疾病确定了更多的中性粒细胞减少症途径：从临床到下一代测序
    摘要：Neutrophils are the most common type of leukocyte in human circulating blood and constitute one of the chief mediators for innate immunity. Defined as a reduction from a normal distribution of values, neutropenia results from a number of congenital and acquired conditions. Neutropenia may be insignificant, temporary, or associated with a chronic condition with or without a vulnerability to life-threatening infections. As an inherited bone marrow failure syndrome, neutropenia may be associated with transformation to myeloid malignancy. Recognition of an inherited bone marrow failure syndrome may be delayed into adulthood. The list of monogenic neutropenia disorders is growing, heterogeneous, and bewildering. Furthermore, greater knowledge of immune-mediated and drug-related causes makes the diagnosis and management of neutropenia challenging. Recognition of syndromic presentations and especially the introduction of next-generation sequencing are improving the accuracy and expediency of diagnosis as well as their clinical management. Furthermore, identification of monogenic neutropenia disorders is shedding light on the molecular mechanisms of granulopoiesis and myeloid malignancies.
  • 3.

    【2hr】Chronic neutropenia in LGL leukemia and rheumatoid arthritis

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    机译 LGL白血病和类风湿关节炎的慢性中性粒细胞减少
    摘要：This section reviews the diagnostic criteria and pathogenesis of large granular lymphocyte (LGL) leukemia. There is a particular focus on the overlap of LGL leukemia and rheumatoid arthritis (Felty's syndrome). Current understanding of the mechanisms of neutropenia in these disorders is discussed. Finally, treatment indications and therapeutic recommendations are outlined.
  • 4.

    【2hr】Non–chemotherapy drug–induced neutropenia: key points to manage the challenges

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    机译 非化学疗法引起的中性粒细胞减少症：应对挑战的关键点
    • 作者：Brian R. Curtis
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Non–chemotherapy idiosyncratic drug–induced neutropenia (IDIN) is a relatively rare but potentially fatal disorder that occurs in susceptible individuals, with an incidence of 2.4 to 15.4 cases per million population. Affected patients typically experience severe neutropenia within several weeks to several months after first exposure to a drug, and mortality is ∼5%. The drugs most frequently associated with IDIN include metamizole, clozapine, sulfasalazine, thiamazole, carbimazole, amoxicillin, cotrimoxazole, ticlopidine, and valganciclovir. The idiosyncratic nature of IDIN, the lack of mouse models and diagnostic testing, and its low overall incidence make rigorous studies to elucidate possible mechanisms exceptionally difficult. An immune mechanism for IDIN involving neutrophil destruction by hapten (drug)-specific antibodies and drug-induced autoantibodies is frequently suggested, but strong supporting evidence is lacking. Although laboratory testing for neutrophil drug-dependent antibodies is rarely performed because of the complexity and low sensitivity of tests currently in use, these assays could possibly be enhanced by using reactive drug metabolites in place of the parent drug. Patients typically experience acute, severe neutropenia, or agranulocytosis (<0.5 × 109 neutrophils/L) and symptoms of fever, chills, sore throat, and muscle and joint pain. Diagnosis can be difficult, but timely recognition is critical because if left untreated, there is an increase in mortality. Expanded studies of the production and mechanistic role of reactive drug metabolites, genetic associations, and improved animal models of IDIN are essential to further our understanding of this important disorder.
  • 5.

    【2hr】Shall we treat smoldering multiple myeloma in the near future?

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    机译 我们在不久的将来可以治疗阴燃多发性骨髓瘤吗？
    • 作者：Ola Landgren
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：In recent years, several new drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are highly efficacious and less toxic than older chemotherapy drugs. In 2014, the diagnostic criteria for multiple myeloma were revised. The intent with the new criteria was to identify patients who require therapy at an earlier stage than at manifestation of organ complications. A subset of patients who were previously defined as having high-risk smoldering multiple myeloma was redefined as having multiple myeloma. In this context, it is logical to raise questions regarding the optimal clinical management of patients who are diagnosed with smoldering multiple myeloma in the current era. When is the optimal time to start therapy? Do the clinical trajectories for patients suggest there are distinct sub-entities hidden in the current category of smoldering multiple myeloma? How can we move the field forward from here? This paper reviews and dissects data and models on the topics of clinical features, underlying biology, and early treatment trials in smoldering multiple myeloma. The text highlights assumptions, facts, and gaps in the literature. As indicated in the title of the paper, the recurrent theme of the text is this: shall we treat smoldering multiple myeloma in the near future?
  • 6.

    【2hr】Is molecular remission the goal of multiple myeloma therapy?

    包量

    机译 分子缓解是多发性骨髓瘤治疗的目标吗？
    • 作者：Faith E. Davies
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：The increased number of effective therapies and the wider use of combinations that give deeper remissions have resulted in a reassessment of the goals of myeloma therapy. With the advent of new therapeutic strategies and diagnostic tools, achievement of minimal residual disease (MRD)-negative status has become increasingly important, with some even considering it as the primary endpoint for therapy. The level of MRD that is aimed for is a continuous, rather than an absolute variable, with studies in both transplant-eligible and -noneligible patients showing that the level of MRD achieved is predictive of progression-free survival and overall survival, with an improvement in survival of approximately 1 year for each log-depletion in MRD level. The most widely used methods to assess MRD status include flow cytometry and clonality detection, using next-generation sequencing technologies with sensitivity limits of 1:10−3 to 1:10−6. The timing of when to assess MRD depends on the treatment used, as well as the molecular and cytogenetic subgroup of the myeloma itself. It is also becoming clear that the level of MRD negativity, as well as microenvironmental factors, are important prognostically, including the regeneration of normal plasma cells, and the normalization of the immune repertoire. With advances in antibody-based therapy and immunotherapy, the achievement of stable MRD states is now possible for a significant proportion of patients, and is a prerequisite for myeloma cure.
  • 7.

    【2hr】Fixed duration vs continuous therapy in multiple myeloma

    包量

    机译 固定时间与多发性骨髓瘤持续治疗
    • 作者：Heinz LudwigNiklas Zojer
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：The introduction of new drugs with less severe toxicity profiles than those of conventional antimyeloma agents allowed the evaluation of continuous therapy compared with fixed duration therapy. In transplant-eligible patients, consolidation therapy with bortezomib or bortezomib-based regimens showed significant progression-free survival (PFS) benefit in cytogenetic standard-risk patients and to a lesser extent, high-risk patients. Continuous therapy with lenalidomide maintenance treatment after autologous stem cell transplantation resulted in a significant survival gain. In transplant noneligible patients, continuous lenalidomide-dexamethasone therapy improved survival over fixed duration melphalan-prednisone-thalidomide. The concept of prolonged treatment in elderly patients is supported by some other studies, but most of them revealed a gain in PFS only. Young patients with unfavorable prognosis show a greater willingness to accept long-term treatment, whereas the readiness to undergo such treatments and the benefits therefrom decline with increasing age and decreasing fitness, rendering fixed duration therapy a suitable option in elderly frail patients.
  • 8.

    【2hr】Controversies in venous thromboembolism: to treat or not to treat superficial vein thrombosis

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    机译 静脉血栓栓塞的争议：治疗或不治疗浅表静脉血栓形成
    • 作者：Jan Beyer-Westendorf
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：The management of superficial vein thrombosis (SVT) is poorly defined and remains controversial overall. SVT has long been considered a benign, self-limited disease, but recent studies show that SVT carries a nonnegligible risk for recurrence, deep vein thrombosis, or pulmonary embolism. Current guidelines recommend the use of low-molecular-weight heparin or fondaparinux, but results of several surveys indicate that the majority of patients with SVT receive nonanticoagulant therapy only, which includes compression stockings or bandages, nonsteroidal anti-inflammatory drugs, topical application of heparin gel, or surgical interventions. However, several recent observational and interventional studies provide better insight into the optimal treatment of patients with SVT who are at different risks for thromboembolic complications. This educational review summarizes the available evidence and aims to provide practical guidance based on a clinical decision pathway.
  • 9.

    【2hr】Should we diagnose and treat distal deep vein thrombosis?

    包量

    机译 我们应该诊断和治疗远端深静脉血栓形成吗？
    摘要：Ultrasound series report that isolated distal deep vein thrombosis (DVT), also known as calf DVT, represents up to 50% of all lower-limb DVTs and, therefore, is a frequent medical condition. Unlike proximal DVT and pulmonary embolism, which have been studied extensively and for which management is well standardized, much less is known about the optimal management of isolated calf DVT. Recent data arising from registries and nonrandomized studies have suggested that most distal DVTs do not extend to the proximal veins and have an uneventful follow-up when left untreated. These data had some impact on the international recommendations that recently stated that ultrasound surveillance instead of systematic therapeutic anticoagulation might be an option for selected low-risk patients. However, robust data from randomized studies are scarce. Only 5 randomized trials assessing the need for anticoagulation for calf DVT have been published. Many of these trials had an open-label design and were affected by methodological limitations. The only randomized placebo-controlled trial included low-risk patients (outpatients without cancer or previous venous thromboembolism [VTE]) and was hampered by limited statistical power. Nevertheless, data from this trial confirmed that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE but is associated with a significantly higher risk of bleeding. Further randomized studies are needed to define the best therapy for high-risk patients (inpatients, patients with active cancer, or patients with previous VTE) and the optimal dose and duration of treatment.
  • 10.

    【2hr】Symptomatic subsegmental pulmonary embolism: to treat or not to treat?

    包量

    机译 有症状的节段性肺栓塞：治疗还是不治疗？
    摘要：The introduction of computed tomographic pulmonary angiography and its recent increasing availability has led to a significant rise in its use to help clinicians diagnose acute pulmonary embolism (PE). This has led to a significant increase in the incidence of PE diagnoses. Simultaneously, the case fatality rate of acute PE has been decreasing and no significant change in its mortality has been noted, suggesting that the additional PE diagnoses are less severe and these patients might not benefit from anticoagulation therapy. This also seems to be correlated with an increase in the diagnosis of PE localized in the subsegmental pulmonary arteries (subsegmental pulmonary embolism [SSPE]). The clinical importance of SSPE is unclear. Whereas some studies have shown that it might be reasonable to manage patients with SSPE without anticoagulation, others have not. Although the current medical literature is limited, it suggests that a subgroup of patients with SSPE might be safely managed without the use of anticoagulant therapy. Current clinical practice guidelines suggest that clinicians take an individualized approach after carefully assessing the risk/benefit ratio for patients with SSPE and negative leg limb ultrasonography results. Prospective studies are ongoing and results are eagerly awaited to help tailor the management of this patient population.
  • 11.

    【2hr】Pediatric leukemia susceptibility disorders: manifestations and management

    包量

    机译 小儿白血病易感性疾病：表现和管理
    摘要：The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.
  • 12.

    【2hr】Crisis management in the treatment of childhood acute lymphoblastic leukemia: putting right what can go wrong (emergency complications of disease and treatment)

    包量

    机译 儿童急性淋巴细胞白血病的治疗中的危机管理：纠正可能出问题的地方（疾病和治疗的紧急并发症）
    • 作者：Rachael HoughAjay Vora
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：The improvement in overall survival in children with acute lymphoblastic leukemia (ALL) over the last 5 decades has been considerable, with around 90% now surviving long term. The risk of relapse has been reduced to such an extent that the risk of treatment-related mortality is now approaching that of mortality caused by relapse. Toxicities may also lead to the suboptimal delivery of chemotherapy (treatment delays, dose reductions, dose omissions), potentially increasing relapse risk, and short- and long-term morbidity, adding to the “burden of therapy” in an increasing number of survivors. Thus, the need to reduce toxicity in pediatric ALL is becoming increasingly important. This work focuses on the risk factors, pathogenesis, clinical features, and emergency management of the life-threatening complications of ALL at presentation and during subsequent chemotherapy, including leucostasis, tumor lysis syndrome, infection, methotrexate encephalopathy, thrombosis, and pancreatitis. Potential strategies to abrogate these toxicities in the future are also discussed.
  • 13.

    【2hr】Incorporation of nonchemotherapeutic agents in pediatric acute lymphoblastic leukemia

    包量

    机译 非化学治疗药物在小儿急性淋巴细胞白血病中的应用
    • 作者：Lewis B. Silverman
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：With current available therapies, the prognosis for most children and adolescents with acute lymphoblastic leukemia (ALL) is favorable. However, the multiagent chemotherapy regimens used to treat newly diagnosed patients are associated with many acute and long-term complications, and therapy for relapsed disease is intensive and suboptimally effective. Over the last decade, several nonchemotherapeutic approaches have been evaluated, with the goal of identifying more effective, less toxic therapies that can be used in conjunction with, or even replace, current regimens. Novel nonchemotherapeutic therapies with activity in ALL include (1) tyrosine kinase inhibitors in high-risk patient subsets in whom potentially targetable alterations have been identified and (2) immunotherapeutic approaches, such as monoclonal antibodies, immunotoxins, bispecific T-cell–engaging antibodies, and chimeric antigen receptor T cells. This review summarizes promising results from recent clinical trials of these novel treatments.
  • 14.

    【2hr】Iron overload in thalassemia: different organs at different rates

    包量

    机译 地中海贫血中的铁超负荷：不同器官的发生率不同
    摘要：Thalassemic disorders lie on a phenotypic spectrum of clinical severity that depends on the severity of the globin gene mutation and coinheritance of other genetic determinants. Iron overload is associated with increased morbidity in both patients with transfusion-dependent thalassemia (TDT) and non–transfusion-dependent thalassemia (NTDT). The predominant mechanisms driving the process of iron loading include increased iron burden secondary to transfusion therapy in TDT and enhanced intestinal absorption secondary to ineffective erythropoiesis and hepcidin suppression in NTDT. Different organs are affected differently by iron overload in TDT and NTDT owing to the underlying iron loading mechanism and rate of iron accumulation. Serum ferritin measurement and noninvasive imaging techniques are available to diagnose iron overload, quantify its extent in different organs, and monitor clinical response to therapy. This chapter discusses the general approach to iron chelation therapy based on organ involvement using the available iron chelators: deferoxamine, deferiprone, and deferasirox. Other novel experimental options for treatment and prevention of complications associated with iron overload in thalassemia are briefly discussed.
  • 15.

    【2hr】Impact of bone disease and pain in thalassemia

    包量

    机译 地中海贫血中骨病和疼痛的影响
    • 作者：Antonio Piga
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Conventional treatment of thalassemia, namely regular blood transfusion and iron chelation, improves perspectives and quality of life; however, successful treatment leads to more time in which long-term complications such as bone disease can develop. Thalassemia bone disease (TBD) is unique: all aspects, from bone anatomy and bone quality to mineral density, may be affected, with important morbidity including osteoporosis, fractures, spinal deformities, nerve compression, and pain. Clinical presentations include growth impairment, rickets-like features, back pain, spinal deformities, any sign of nerve compression, severe osteoporosis, and fragility fractures. Age, history, physical examination, and diagnostic tests support orientation on risk factors. These include bone marrow expansion, toxicity from iron overload and iron chelation, endocrine dysfunctions (hypogonadism, hypohyperparathyroidism, hypothyroidism, growth hormone deficiency, diabetes), and vitamin (D, C, K) and zinc deficiencies. Several of these may coexist in an individual for a long time and at different degrees, making clarification of the relative contribution and selection of the best therapeutic options a challenge. Milestones for prevention of TBD are early and full inhibition of bone marrow hyperplasia and iron toxicity. Empowering patients’ positive resources is key for achieving long-term healthy habits with regard to diet, physical activity, sunlight exposure, and lifestyle. Pain, related or unrelated to bone disease, is frequent in thalassemia. The most important targets for the hematologist include having an expert orientation on disease-related causes of pain, driving differential diagnosis, providing effective pain relief and, where feasible, removing the cause.
  • 16.

    【2hr】New therapeutic targets in transfusion-dependent and -independent thalassemia

    包量

    机译 输血依赖性和非依赖性地中海贫血的新治疗靶点
    摘要：β-Thalassemias are characterized by reduced production of β-globin chain, resulting in α/β-chain unbalance and precipitation of α-globin–heme complexes and determining ineffective erythropoiesis. Ineffective erythropoiesis, chronic hemolytic anemia, and compensatory hematopoietic expansion are the disease hallmarks, and they are related to the severity of the chain unbalance. Several clinical forms of β-thalassemia, including the coinheritance of β-thalassemia with hemoglobin E resulting in hemoglobin E/β-thalassemia, have been described. Clinically, β-thalassemias can be classified as transfusion-dependent thalassemia (TDT) and non–transfusion-dependent thalassemia (NTDT) according to the severity of the phenotype, which is caused by a wide spectrum of mutations in a homozygous or compound heterozygous state. Current treatment of TDT consists of regular transfusions that lead to iron overload, requiring iron chelation to prevent iron-related organ toxicity. NTDT patients do not require transfusions or only occasionally require them; however, they develop iron overload as well because of increased intestinal iron absorption caused by chronic anemia. Hematopoietic stem cell allogenic transplant is the only approved cure for β-thalassemia; however, it is still limited by clinical conditions and the availability of matched donors as well as by potential graft-versus-host disease (GVHD). Gene therapy could avoid the GVHD risk, although hematopoietic stem cells must be genetically modified ex vivo. Epigenetic manipulation and genomic editing are novel experimental approaches. An increased understanding of the pathophysiology that controls the disease process prompted us to explore alternative therapeutic approaches that address the underlying chain unbalance, ineffective erythropoiesis, and iron dysregulation. Molecules, such as JAK2 inhibitors and the activin-receptor ligand trap that target ineffective erythropoiesis, are already in clinical trials with promising results. Other agents aimed to generate iron-restricted erythropoiesis are also under experimental evaluation.
  • 17.

    【2hr】Tailoring front-line therapy in diffuse large B-cell lymphoma: who should we treat differently?

    包量

    机译 在弥漫性大B细胞淋巴瘤中量身定制一线疗法：我们应该对谁进行不同的治疗？
    • 作者：Andrew Davies
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Although there have been significant insights into the biology of diffuse large B-cell lymphoma (DLBCL) over recent years, progress in our therapeutic approach has been disappointing over the same timeframe. This is not for want of trying. In 2017, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the “gold standard,” despite all of our insights into cell-of-origin and other subgroups. We have traditionally used clinical risk factors to tailor our therapies and have tested intensification of chemotherapy with little success. We are now in an era of testing therapies according to the molecular phenotype of the individual’s tumor. Many phase 1/2 studies have looked at adding targeted agents to conventional R-CHOP with some promise. The phase 3 data are now starting to emerge. Are we ready yet to modify our standard of care and have we reached an era of precision medicine in DLBCL? The answer to this is “not yet.” The exception is perhaps patients with the newly defined World Health Organization category of high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, the so-called double- and triple-hit lymphomas. In these tumors there has been a move away from R-CHOP to more intensified regimens, however, has not been based upon rigorous prospective evaluation but review of retrospective datasets. This article will review the molecular subgroups of DLBCL, interventional strategies, and the outcomes of these interventions to date.
  • 18.

    【2hr】Current treatment of double hit and double expressor lymphoma

    包量

    机译 双发和双表达淋巴瘤的当前治疗方法
    摘要：A 60-year-old female presented with abdominal pain and distension. Following computed tomography scans of the abdomen and pelvis, she was taken urgently to the operating room, with the belief that she had appendicitis with perforation. At laparotomy, the findings were consistent with an ovarian carcinoma; there was extensive infiltration of the ovary, bowel, and omental deposits. Cytoreductive surgery was performed including total abdominal hysterectomy and bilateral salpingo-oophorectomy. The final pathology, however, revealed infiltration with medium-sized atypical lymphoid cells positive for CD20, CD10, MYC, BLC2, and BCL6 by immunohistochemistry. MYC and BCL2 translocations were identified by fluorescence in situ hybridization consistent with a diagnosis of high-grade B-cell lymphoma with rearrangements of MYC and BCL2. With the current data available, what is the optimal treatment of this patient?
  • 19.

    【2hr】Primary mediastinal B-cell lymphoma: biology and evolving therapeutic strategies

    包量

    机译 原发性纵隔B细胞淋巴瘤：生物学和不断发展的治疗策略
    • 作者：Kieron Dunleavy
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Primary mediastinal B-cell lymphoma (PMBCL) is recognized as a distinct clinicopathologic entity that predominantly affects adolescents and young adults and is more common in female subjects. Although PMBCL is considered to be a subtype of diffuse large B-cell lymphoma, its clinical, morphologic, and biological characteristics overlap significantly with those of nodular sclerosing Hodgkin lymphoma (NSHL). Over the past few years, the shared biology of these 2 entities has been highlighted in several studies, and mediastinal gray zone lymphoma, with features intermediate between PMBCL and NSHL, has been recognized as a unique molecular entity. Although there is a lack of consensus about the optimal therapeutic strategy for adolescent and young adult patients newly diagnosed with PMCBL, highly curative strategies that obviate the need for mediastinal radiation are favored by most. Progress in understanding the biology of PMBCL and its close relationship to NSHL have helped pave the way for the investigation of novel approaches such as immune checkpoint inhibition. Other strategies such as adoptive T-cell therapy and targeting CD30 are also being studied.
  • 20.

    【2hr】Optimizing therapy for mantle cell lymphoma

    包量

    机译 优化套细胞淋巴瘤的治疗
    • 作者：Peter Martin
    • 刊名：Hematology: the American Society of Hematology Education Program
    • 2017年第1期
    摘要：Most people with mantle cell lymphoma (MCL) present with diffuse adenopathy and benefit from early initiation of rituximab and high-dose cytarabine- or bendamustine-based therapies. Some patients, however, present with primarily nonnodal disease that can follow either an indolent or a rapidly progressive, treatment-resistant clinical course. Rarely, patients present with explosive disease that can be challenging to manage and often involves the central nervous system. New agents with improved therapeutic indices facilitate treatment while maintaining quality of life, but also present new complications at the time of treatment failure. Although uncommon presentations are not new to clinicians who treat MCL, the increasing clarity of underlying biology and prognostic implications may help us develop more specialized treatment strategies.
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