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AL amyloidosis: from molecular mechanisms to targeted therapies.
Authors: Merlini G Abstract 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 preve...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation.
Authors: Brüggemann M, Kotrova M Abstract 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 im...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Current management of Philadelphia chromosome positive ALL and the role of stem cell transplantation.
Authors: Ravandi F Abstract 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, particul...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Progress in adult ALL: incorporation of new agents to frontline treatment.
Authors: Leonard J, Stock W Abstract 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. Addition...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Classification and risk assessment in AML: integrating cytogenetics and molecular profiling.
Authors: Moarii M, Papaemmanuil E Abstract 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. PMID: 29222235 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

How and when to decide between epigenetic therapy and chemotherapy in patients with AML.
Authors: Dombret H, Itzykson R Abstract 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 th...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

The role of targeted therapy in the management of patients with AML.
Authors: Perl AE Abstract 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. PMID: 29222237 [PubMed -...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Clinical implications of somatic mutations in aplastic anemia and myelodysplastic syndrome in genomic age.
Authors: Maciejewski JP, Balasubramanian SK Abstract 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, ...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Aging, hematopoiesis, and the myelodysplastic syndromes.
Authors: Chung SS, Park CY Abstract 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 incre...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Old and new tools in the clinical diagnosis of inherited bone marrow failure syndromes.
Authors: West AH, Churpek JE Abstract 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 outc...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Inherited bone marrow failure syndromes: considerations pre- and posttransplant.
Authors: Alter BP Abstract 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...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Treatment of inherited bone marrow failure syndromes beyond transplantation.
Authors: Calado RT, Clé DV Abstract 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 toxici...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Treatment-free remission in CML: who, how, and why?
Authors: Mahon FX Abstract 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...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Cardiovascular care of patients with chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) therapy.
Authors: Barber MC, Mauro MJ, Moslehi J Abstract 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.&quo...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Novel approaches to therapy in CML.
Authors: Bhatia R Abstract 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...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Incidental venous thromboembolism: is anticoagulation indicated?
Authors: Di Nisio M, Carrier M Abstract 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 arte...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

When can we stop anticoagulation in patients with cancer-associated thrombosis?
Authors: Lee AYY Abstract 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 epidemiolo...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Direct oral anticoagulants: now also for prevention and treatment of cancer-associated venous thromboembolism?
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. PMID: 29222248 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Thrombocytopenia in pregnancy.
Authors: Cines DB, Levine LD Abstract 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...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Iron deficiency in gynecology and obstetrics: clinical implications and management.
Authors: Breymann C, Auerbach M Abstract Iron deficiency is the commonest cause of anemia during pregnancy; however, its prevalence is highly determined by nutritional and socioeconomic status. Oral iron is the frontline therapy, but is often poorly tolerated. Awareness of the available intravenous formulations is essential for management. Before delivery, risk factors such as multiparity and heavy uterine bleeding increase the prevalence of iron deficiency and should be motivation for early diagnosis and treatment. Neonates born with iron deficiency have a statistically significant increment in both cognitive and ...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Preventing venous thromboembolism during pregnancy and postpartum: crossing the threshold.
This article will explore the concept of a risk threshold from clinician and patient perspectives and provide guidance for the use of antepartum and postpartum LMWH prophylaxis in women with a known thrombophilia or prior VTE. Advice for the management of LMWH prophylaxis use around labor and delivery is also reviewed. PMID: 29222251 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Diagnosis and management of postpartum ovarian vein thrombosis.
Authors: Bannow BTS, Skeith L Abstract 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? PMID: 29222252 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

New monogenic disorders identify more pathways to neutropenia: from the clinic to next-generation sequencing.
Authors: Corey SJ, Oyarbide U Abstract 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 fa...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Chronic neutropenia in LGL leukemia and rheumatoid arthritis.
Authors: Gazitt T, Loughran TP Abstract 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. PMID: 29222254 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Non-chemotherapy drug-induced neutropenia: key points to manage the challenges.
Authors: Curtis BR Abstract 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...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Shall we treat smoldering multiple myeloma in the near future?
Authors: Landgren O Abstract 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 rega...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Is molecular remission the goal of multiple myeloma therapy?
Authors: Davies FE Abstract 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...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Fixed duration vs continuous therapy in multiple myeloma.
Authors: Ludwig H, Zojer N Abstract 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 trans...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Controversies in venous thromboembolism: to treat or not to treat superficial vein thrombosis.
Authors: Beyer-Westendorf J Abstract 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, topi...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Should we diagnose and treat distal deep vein thrombosis?
Authors: Robert-Ebadi H, Righini M Abstract 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. T...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Symptomatic subsegmental pulmonary embolism: to treat or not to treat?
Authors: Carrier M, Klok FA Abstract 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 ...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Pediatric leukemia susceptibility disorders: manifestations and management.
Authors: McReynolds LJ, Savage SA Abstract 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 ...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Crisis management in the treatment of childhood acute lymphoblastic leukemia: putting right what can go wrong (emergency complications of disease and treatment).
Authors: Hough R, Vora A Abstract 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 n...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Incorporation of nonchemotherapeutic agents in pediatric acute lymphoblastic leukemia.
Authors: Silverman LB Abstract 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 nonchemot...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Iron overload in thalassemia: different organs at different rates.
Authors: Taher AT, Saliba AN Abstract 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....
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Impact of bone disease and pain in thalassemia.
Authors: Piga A Abstract 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 si...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

New therapeutic targets in transfusion-dependent and -independent thalassemia.
Authors: Cappellini MD, Motta I Abstract 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 descr...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Tailoring front-line therapy in diffuse large B-cell lymphoma: who should we treat differently?
This article will review the molecular subgroups of DLBCL, interventional strategies, and the outcomes of these interventions to date. PMID: 29222268 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Current treatment of double hit and double expressor lymphoma.
Authors: Reagan PM, Davies A Abstract 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 c...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Primary mediastinal B-cell lymphoma: biology and evolving therapeutic strategies.
Authors: Dunleavy K Abstract 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 an...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Optimizing therapy for mantle cell lymphoma.
Authors: Martin P Abstract 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 ...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.
Authors: Liu WR, Shipp MA Abstract Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, ...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Emerging role of novel therapies in Hodgkin lymphoma: proceed with caution.
Authors: Bartlett NL Abstract Based on very high response rates in the relapsed and refractory setting, brentuximab vedotin and the programmed cell death protein 1 (PD-1) inhibitors, nivolumab and pembrolizumab, have quickly been incorporated into clinical trials for first- and second-line therapy of Hodgkin lymphoma. Preliminary data show that brentuximab vedotin alone is not adequate therapy for newly diagnosed Hodgkin lymphoma in older patients, but modestly decreases the risk of relapse when combined with adriamycin, vinblastine, and dacarbazine in patients with previously untreated advanced-stage disease. In s...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management.
Authors: Eichenauer DA, Engert A Abstract Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological and clinical features. Histologically, the disease-defining lymphocyte predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL mostly has a rather indolent course, and patients usually are diagnosed in early stages. The prognosis of early-stage NLPHL is excellent, with progression-free survival and overall s...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

The mutational landscape of chronic lymphocytic leukemia and its impact on prognosis and treatment.
Authors: Gaidano G, Rossi D Abstract The typical genome of chronic lymphocytic leukemia (CLL) carries ∼2000 molecular lesions. Few mutations recur across patients at a frequency>5%, whereas a large number of biologically and clinically uncharacterized genes are mutated at lower frequency. Approximately 80% of CLL patients carry at least 1 of 4 common chromosomal alterations, namely deletion 13q14, deletion 11q22-23, deletion 17p12, and trisomy 12. Knowledge of the CLL genome has translated into the availability of molecular biomarkers for prognosis and treatment prediction. Prognostic biomarkers do not affec...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Optimizing frontline therapy of CLL based on clinical and biological factors.
Authors: Fischer K, Hallek M Abstract The heterogeneity of the clinical course of chronic lymphocytic leukemia (CLL) ranges from an indolent course, where patients do not require therapy for many years, to a very aggressive disease, where treatment is required soon after diagnosis and relapses may occur early. The improved tools for prognostication allow predicting the outcome of patients with increasing reliability. Some markers also allow selecting more specific therapies with improved activity in the presence of certain genetic or clinical features of CLL. Of these markers, TP53 dysfunction, age, the presence of...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

How should we sequence and combine novel therapies in CLL?
Authors: Davids MS Abstract With the recent approval of several effective and well-tolerated novel agents (NAs), including ibrutinib, idelalisib, venetoclax, and obinutuzumab, patients with chronic lymphocytic leukemia (CLL) have more therapeutic options than ever before. The availability of these agents is both an important advance for patients but also a challenge for practicing hematologist/oncologists to learn how best to sequence NAs, both with respect to chemoimmunotherapy (CIT) and to other NAs. The sequencing of NAs in clinical practice should be guided both by an individual patient's prognostic markers, su...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Safety profiles of novel agent therapies in CLL.
Authors: Ahn IE, Davids MS Abstract A 70-year-old man with relapsed/refractory chronic lymphocytic leukemia has multiple comorbidities including atrial fibrillation (on warfarin for anticoagulation), irritable bowel syndrome, and chronic renal insufficiency. Two years ago, he received bendamustine and rituximab as first-line therapy for chronic lymphocytic leukemia and achieved partial response, but now has relapsed. Fluorescence in situ hybridization cytogenetics reveals deletion 17p. Which novel agent would you recommend for this patient? PMID: 29222278 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Follicular lymphoma: are we ready for a risk-adapted approach?
Authors: Kahl BS Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historicall...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Toward personalized treatment in Waldenstr öm macroglobulinemia.
Toward personalized treatment in Waldenström macroglobulinemia. Hematology Am Soc Hematol Educ Program. 2017 Dec 08;2017(1):365-370 Authors: Castillo JJ, Treon SP Abstract Waldenström macroglobulinemia (WM) is a rare lymphoma with 1000 to 1500 new patients diagnosed per year in the United States. Patients with WM can experience prolonged survival times, which seem to have increased in the last decade, but relapse is inevitable. The identification of recurrent mutations in the MYD88 and CXCR4 genes has opened avenues of research to better understand and treat patients with WM. These developmen...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research