Scherber RM, Mesa RA. Managing myelofibrosis (MF) that "blasts" through: advancements in the treatment of relapsed/refractory and blast-phase MF. Hematology Am Soc Hematol Educ Program. 2018;2018:118-126.
Scherber RM, Mesa RA. Managing myelofibrosis (MF) that "blasts" through: advancements in the treatment of relapsed/refractory and blast-phase MF. Hematology Am Soc Hematol Educ Program. 2018;2018:118-126. Hematology Am Soc Hematol Educ Program. 2019 Dec 06;2019(1):630 Authors: PMID: 31808826 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Novel agents and immune invasion in Hodgkin lymphoma.
Authors: Merryman RW, LaCasce A Abstract The approval of brentuximab vedotin (BV) and the PD-1 inhibitors nivolumab and pembrolizumab has dramatically improved outcomes for patients with relapsed or refractory (R/R) classic Hodgkin lymphoma (HL). With the goal of increasing long-term disease control rates and decreasing late toxicities, these agents are currently being tested in earlier phases of treatment in combination with chemotherapy agents. In the R/R setting, our expanding understanding of HL's various mechanisms of immune evasion and treatment resistance has spurred a growing number of rationally designed c...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Patient blood management as the standard of care.
Authors: Murphy MF, Palmer A Abstract Blood transfusion is one of the most common hospital procedures in developed countries. However, inappropriate use of blood transfusion is common, and this is of considerable concern because transfusion is known to be associated with adverse events and is costly. Reductions in blood use have resulted from recent evidence indicating that restrictive use of red blood cell transfusions is associated with similar patient outcomes to liberal strategies and from a focus on patient blood management (PBM), which recognizes the importance of conserving the patient's own blood alongside ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Emerging strategies in peripheral T-cell lymphoma.
Authors: Mehta-Shah N Abstract Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin lymphomas that are less chemosensitive than their B-cell counterparts. Until recently, standard therapy did not distinguish between subtypes, and deeper understanding of the biology of these diseases was lacking. The availability of targeted therapy and more sophisticated subtype classification has translated into the development of novel treatment options for these rare diseases. This includes the development of a brentuximab vedotin-based upfront chemotherapy regimen that confers an overall surviv...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Cause-specific late mortality after allogeneic stem cell transplantation.
Authors: Bhatia S Abstract Conditional on surviving the first 2 to 5 years after allogeneic blood or marrow transplantation (BMT), the 10-year overall survival approaches 80%. Nonetheless, the risk of late mortality remains higher than the age- and sex-matched general population for several years after BMT. The higher mortality rates in transplant recipients translate into shorter projected life expectancies compared with the general population. Risk of relapse-related mortality reaches a plateau within 10 years after BMT. With increasing time from BMT, nonrelapse-related mortality becomes the leading cause of deat...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

New advances in the diagnosis of von Willebrand disease.
Authors: Sharma R, Haberichter SL Abstract von Willebrand disease (VWD) is the most common autosomal inherited bleeding disorder, with an estimated prevalence of 1 in 1000 individuals. VWD is classified into quantitative and qualitative forms. Diagnosis of VWD is complex and requires (1) a personal history of bleeding symptoms, (2) family history of bleeding or VWD, and (3) confirmatory laboratory testing. There are certain bleeding assessment tools to objectively measure bleeding symptoms in patients that have been shown to correlate with the diagnosis as well as the severity of VWD. Laboratory diagnosis requires ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Optimal disease management and health monitoring in adults with sickle cell disease.
Authors: Howard J, Thein SL Abstract In countries with access to organized health care, survival of children with sickle cell disease (SCD) has greatly improved, resulting in a growing population of adults with SCD. Transition from pediatric to adult care presents many challenges for the patient, who now faces the reality of emerging complications in many organs that are cumulative, adding to other age-related nonsickle conditions that interact and add to the disease morbidity. We recommend regular comprehensive annual assessments, monitoring for early signs of organ damage and joint clinics with relevant specialis...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

What to do with minimal residual disease testing in myeloma.
This article reviews a clinical case in which MRD testing, both in bone marrow and in functional imaging, is part of the standard of care. It also reviews the different modalities of MRD testing and current practice guidelines. Finally, patients with myeloma may be tested for MRD after treatment because this is part of the routine response assessment according to International Myeloma Working Group criteria and correlates with clinical outcomes. Important questions such as when to stop therapy for sustained MRD-negative patients or whether to change treatments for patients who go from MRD negative to positive without other...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Improvements in diagnosis and risk assessment of primary and secondary antiphospholipid syndrome.
Authors: Petri M Abstract Classification criteria for antiphospholipid syndrome have not been updated since the revised Sapporo classification criteria were published in 2006. These criteria have limitations in that they omit nonclassical manifestations (hematologic and neurologic), include anticardiolipin and anti-β2-glycoprotein I immunoglobulin (Ig)M isotypes, and do not separately consider primary (no autoimmune disease) or secondary (usually systemic lupus erythematosus) disease. Recent findings in antiphospholipid antibody include fluctuation of antiphospholipid antibodies, recognition that IgA isotypes ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

What we have learned about direct oral anticoagulant reversal.
Authors: Siegal DM Abstract Bleeding is the main complication of oral anticoagulant (OAC) therapy, with major bleeds occurring in about 2% to 4% of OAC-treated patients per year. Although direct oral anticoagulants (DOACs) reduce the risk of major, fatal, and intracranial hemorrhage, major DOAC-related bleeding is associated with substantial morbidity and mortality, with case-fatality rates of 8% to 15% reported. Specific reversal agents for dabigatran (idarucizumab) and factor Xa inhibitors (andexanet) correct laboratory indices of anticoagulant effect. Clinical studies suggest that the majority of patients receiv...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Prognostication with circulating tumor DNA: is it ready for prime time?
This article discusses the methodology for detecting ctDNA in aggressive B-cell lymphomas, including digital polymerase chain reaction, targeted sequencing of immunoglobulin receptors, and targeted next-generation sequencing. The advantages of each of these methods are also compared, with a focus on promising clinical applications. These include identification of molecular subtypes (eg, cell-of-origin and double-hit lymphomas) from pretreatment plasma, molecular response prediction after an initial course of therapy, and early detection of relapsing disease prior to clinical relapse. Finally, this article discusses the cha...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Perioperative management of patients with von Willebrand disease.
Authors: O'Donnell JS, Lavin M Abstract Surgical procedures represent a serious hemostatic challenge for patients with von Willebrand disease (VWD), and careful perioperative management is required to minimize bleeding risk. Risk stratification includes not only the nature of the surgery to be performed but the baseline plasma von Willebrand factor (VWF) levels, bleeding history, and responses to previous challenges. Baseline bleeding scores (BSs) may assist in identification of patients with a higher risk of postsurgical bleeding. There remains a lack of consensus between best practice guidelines as to the therape...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Cure at what (systemic) financial cost? Integrating novel therapies into first-line Hodgkin lymphoma treatment.
Authors: Huntington SF Abstract Classic Hodgkin lymphoma (cHL) stands out as success story in the field of medical oncology, with multiagent chemotherapy with or without radiation leading to durable remission for most patients. Large-scale clinical trials during the past 40 years have sought to minimize toxicities while maintaining strong efficacy, including efforts to reduce the size of radiation fields, minimize alkylator chemotherapy, reduce the number of chemotherapy cycles, and omit radiation in select populations. The last decade has also ushered in novel therapies, including brentuximab vedotin (BV), that ha...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Genetic predisposition to MDS: diagnosis and management.
Authors: Furutani E, Shimamura A Abstract Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by clonal hematopoiesis with a propensity to evolve into acute myeloid leukemia. MDS presenting in children and young adults is associated with features clinically and biologically distinct from MDS arising in older adults. MDS presenting in children and young adults is associated with a higher likelihood of an underlying genetic predisposition; however, genetic predisposition is increasingly recognized in a subset of older adults. The diagnosis of a genetic predisposition to MDS informs cl...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Diagnostic workflow for hereditary erythrocytosis and thrombocytosis.
Authors: McMullin MF Abstract In the patient presenting with an elevated blood count who does not have an acquired clonal disorder causing a myeloproliferative neoplasm, hereditary erythrocytosis or hereditary thrombocytosis needs to be considered as a possible explanation. A young patient and/or those with a family history of myeloproliferative neoplasm should specifically raise this possibility. Among the causes of hereditary erythrocytosis are mutations in the genes in the oxygen sensing pathway and high-affinity hemoglobins. Hereditary thrombocytosis has been shown to be accounted for by mutations in THPO, MPL,...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Roundtable: How I treat a newly diagnosed patient with high-risk myeloma.
Authors: Kaufman JL Abstract Initial management of high-risk myeloma remains a treatment challenge. Risk is defined by a combination of clinical and biological features, with fluorescence in situ hybridization detection of specific cytogenetic abnormalities driving categorization. High-risk abnormalities include t(4;14), t(14;16), t(14;20), del(17p), and +1q. Clinical features such as plasma cell leukemia, presence of 5% to 20% circulating plasma cells, and extramedullary disease all are factors in high-risk presentations. The driving principle of treatment of the high-risk patient is the use of a regimen with the ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Is there a role for immunosuppression in antiphospholipid syndrome?
Authors: Sevim E, Willis R, Erkan D Abstract Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy morbidity, or nonthrombotic manifestations in patients with persistently positive antiphospholipid antibodies (aPL). Conventional APS treatment focuses on antithrombotic strategies, which are usually ineffective for the microvascular and nonthrombotic manifestations of aPL. Using a case-based presentation, this review focuses on the role of immunosuppression in nonobstetric APS, including B-cell inhibition (rituximab, belimumab, and bortezomib), complement inhibition ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Opportunities for immunotherapy in childhood acute myeloid leukemia.
This article reviews the current landscape of antibody-based and cellular immunotherapies under current clinical evaluation with an emphasis on active or soon-to-open phase 1 trials for children with relapsed/refractory AML. PMID: 31808843 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Targeting CD20: teaching an old dog new tricks.
Authors: Sharman JP Abstract Rituximab was the first monoclonal antibody used for the treatment of a malignancy. In the 22 years since initial approval, it has become a vital component of therapy for a multitude of B-cell malignancies. Within the last several years, however, there has been a robust development of novel agents targeting CD20, including second generation anti-CD20 antibodies, biosimilar antibodies, and subcutaneous formulations that have been approved. The era of passive immunotherapy is now yielding to therapeutic approaches that actively engage the immune system. Emerging approaches leverage immuno...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Management of liver complications in sickle cell disease.
Authors: Suddle AR Abstract Liver disease is an important cause of morbidity and mortality in patients with sickle cell disease (SCD). Despite this, the natural history of liver disease is not well characterized and the evidence basis for specific therapeutic intervention is not robust. The spectrum of clinical liver disease encountered includes asymptomatic abnormalities of liver function; acute deteriorations in liver function, sometimes with a dramatic clinical phenotype; and decompensated chronic liver disease. In this paper, the pathophysiology and clinical presentation of patients with acute and chronic liver...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Case-based discussion on the implications of exogenous estrogens in hemostasis and thrombosis: the hematologist's view.
Authors: Ragni MV Abstract In the childbearing years, hormonal therapy or hormonal changes in the menstrual cycle or the puerperium may be complicated by bleeding or thrombosis; however, among women with congenital disorders of hemostasis and thrombosis, the risk of bleeding or thrombosis may be increased. In women with congenital bleeding disorders, heavy menstrual bleeding is the most common bleeding symptom, and postpartum hemorrhage occurs despite treatment. Given the limitations of current therapy and the associated medical and psychological burden in women with bleeding disorders, better treatment approaches ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Clonal evolution and immune evasion in posttransplantation relapses.
Authors: Vago L Abstract Despite the considerable improvements witnessed over the last few decades in the feasibility and safety of allogeneic hematopoietic cell transplantation (allo-HCT) for hematological malignancies, disease relapse continues to represent a frequent occurrence, with largely unsatisfactory salvage options. Recent studies have shed new light on the biology of posttransplantation relapses, demonstrating that they can frequently be explained using an evolutionary perspective: The changes in disease clonal structure and immunogenicity that are often documented at relapse may in fact represent the en...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Management of rare acquired bleeding disorders.
Authors: Menegatti M, Biguzzi E, Peyvandi F Abstract Autoantibodies toward clotting factors may develop in people suffering from autoimmune or neoplastic diseases, after drug intake or even in subjects without apparent conditions. They are more commonly directed against factor VIII (FVIII) or von Willebrand factor leading to acquired hemophilia A or acquired von Willebrand syndrome, respectively. Rarely, autoantibodies develop against other clotting factors, such as fibrinogen, FII, FV, FVII, FX, FXI, and FXIII. The clinical picture of an acquired bleeding disorder includes a wide spectrum of clinical manifestation...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Evidence-Based Minireview: Mortality and thrombosis in patients receiving prothrombin complex concentrates or andexanet alfa for the management of direct oral factor Xa inhibitor-associated major bleeding.
Authors: Kimpton M, Siegal DM Abstract A 77-year-old man with atrial fibrillation and a CHA2DS2Vasc score of 6 for hypertension, age, diabetes, and previous stroke is brought to the emergency department with decreased level of consciousness. He is anticoagulated with rivaroxaban (a direct oral factor Xa inhibitor [FXaI]) and received his last dose about 4 hours before presentation. Urgent computed tomography of the head shows intracerebral hemorrhage. Because of his previous stroke, the patient's family is concerned about treating the bleed with pharmacological agents that may increase the risk of stroke. What are ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

How I treat a refractory myeloma patient who is not eligible for a clinical trial.
Authors: Leng S, Bhutani D, Lentzsch S Abstract Myeloma patients not eligible for clinical trials have many treatment options. Choosing the next best therapy starts with careful assessment of the biology and dynamics of the disease at relapse, as well as the condition and situation of the patient. Fit patients should be considered for triplet regimens, whereas intermediate and frail patients warrant dose-reduced triplets or doublets. An indolent serologic relapse may be treated with dose intensification, especially in a maintenance situation, whereas a rapid relapse requires a more aggressive approach with drug cla...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Optimizing cord blood selection.
Authors: Ruggeri A Abstract Nowadays a donor can be found for virtually all patients in need of an allogeneic stem cell transplantation, and the decision whether to use a matched or mismatched unrelated donor, an unrelated donor for umbilical cord blood transplantation (UCBT), or a haploidentical donor depends not only on the availability of the donor but also on patient-, disease-, and center-related factors. This paper summarizes the recent criteria in the selection of cord blood unit, including the cell dose requirement and the HLA typing for the optimal donor choice. The main strategies to optimize the results ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Beyond JAK-STAT: novel therapeutic targets in Ph-negative MPN.
This article reviews the successes and limitations of JAK-STAT inhibition, surveys the strategies behind emerging therapies, and discusses the challenges that are present in moving beyond JAK-STAT. PMID: 31808852 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Evidence-Based Minireview: Does achieving MRD negativity after initial therapy improve prognosis for high-risk myeloma patients?
Authors: Sidana S, Manasanch E Abstract You are evaluating a 47-year-old man with revised international staging system stage III myeloma who recently underwent an autologous stem cell transplant after receiving 6 cycles of carfilzomib, lenalidomide, and dexamethasone for newly diagnosed disease. Fluorescence in situ hybridization testing at initial presentation also revealed t(4;14). On day 100 evaluation after transplant, he has achieved a stringent complete response. Two-tube, 8-color advanced flow cytometry with a sensitivity of 10-5 shows no minimal residual disease. Whole-body positron emission tomography/comp...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Indolent lymphomas: pushing the pace with novel agents.
Authors: Jacobson CA Abstract Chemoimmunotherapy has been a hallmark of treatment of indolent B-cell non-Hodgkin lymphomas for the past 2 decades, with high response rates seen but relapses nearly inevitable and patients spending, on average, 20 years on and off treatment. Treatment advances, then, should be aimed at maintaining efficacy while minimizing toxicity or at achieving cure. Improved understanding of the genetic and molecular features of these diseases, as well as of the interaction between the tumor cell and its immune microenvironment, has resulted in an accelerated expansion of tolerable treatment opti...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Bleeding in critical care associated with left ventricular assist devices: pathophysiology, symptoms, and management.
Authors: Leebeek FWG, Muslem R Abstract Chronic heart failure (HF) is a growing health problem, and it is associated with high morbidity and mortality. Left ventricular assist devices (LVADs) are nowadays an important treatment option for patients with end-stage HF not only as a bridging tool to heart transplantation but also, as a permanent therapy for end-stage HF (destination therapy). The use of LVAD is associated with a high risk for bleeding complications and thromboembolic events, including pump thrombosis and ischemic stroke. Bleeding is the most frequent complication, occurring in 30% to 60% of patients, b...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Osteonecrosis in sickle cell disease: an update on risk factors, diagnosis, and management.
We present the case of a young woman with bilateral osteonecrosis of the femoral head at varying stages of progression; we also highlight other important comorbid complications (eg, chronic pain requiring long-term opioids, debility, and social isolation) and postoperative outcomes. In this review, partly based on recommendations on osteonecrosis management from the 2014 evidence-based report on sickle cell disease from the National Heart, Lung and Blood Institutes, we also discuss early signs or symptoms of osteonecrosis of the femoral head, radiographic diagnosis and staging criteria, hydroxyurea effect on progression to...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Evidence-Based Minireview: Longitudinal geriatric assessment in quality care for older patients with hematologic malignancies.
Authors: Lin RJ, Klepin HD Abstract A 65-year-old women was diagnosed with acute myeloid leukemia (AML; normal cytogenetics, NPM1 mutated, FLT3-ITD wild type). Preinduction screening geriatric assessment (GA) did not reveal any significant deficit, because she was independent of basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs), had normal cognition, and scored 10 (range 0-12) on the short physical performance battery (SPPB). She underwent standard 7 + 3 induction and achieved a complete remission, although her course was complicated by neutropenic sepsis and bacteremia. Sh...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

What's new in the prevention and treatment of cancer-associated thrombosis?
Authors: Kimpton M, Carrier M Abstract Venous thromboembolism (VTE) is a common complication in ambulatory cancer patients receiving chemotherapy. Current clinical guidelines recommend against the use of routine primary thromboprophylaxis in unselected ambulatory cancer patients. The Khorana score is a risk assessment tool derived and prospectively validated for the identification of cancer patients at high risk of thrombotic complications. Recently, 2 randomized, controlled trials have assessed the use of low-dose direct oral Xa inhibitors, apixaban and rivaroxaban, for the prevention of cancer-associated thrombos...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Myeloma: next generation immunotherapy.
Authors: Cohen AD Abstract The course of multiple myeloma (MM) from initial diagnosis to a relapsed/refractory state is characterized by acquisition of drug resistance as well as progressive immunologic dysfunction. Despite this, however, a number of novel therapies that work in part or solely via immune stimulation are in development for MM, with promising early clinical results. Several new whole-cell or multiepitope vaccine approaches are demonstrating immunologic efficacy in smoldering MM or as posttherapy consolidation, with trials ongoing to see whether this translates into delayed progression or elimination ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Where does transplant fit in the age of targeted therapies?
Authors: Chow VA, Gopal AK Abstract The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Microbiota modification in hematology: still at the bench or ready for the bedside?
Authors: Severyn CJ, Brewster R, Andermann TM Abstract Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we ev...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Minimal residual disease and stem cell transplantation outcomes.
Authors: Cloos J, Ossenkoppele GJ, Dillon R Abstract Risk classification and tailoring of treatment are essential for improving outcome for patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Both patient and leukemia-specific characteristics assessed using morphology, cytogenetics, molecular biology, and multicolor flow cytometry are relevant at diagnosis and during induction, consolidation, and maintenance phases of the treatment. In particular, minimal residual disease (MRD) during therapy has potential as a prognostic factor of outcome, determination of response to therapy, and direction...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Evidence-Based Minireview: What is the optimal timing of anti-PD-1 antibodies in relapsed classical Hodgkin lymphoma?
Authors: Allen PB, LaCasce AS Abstract A 26-year-old woman was initially diagnosed with stage III classical Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for 6 cycles and relapsed 9 months after completing therapy. She was treated with salvage chemotherapy followed by an autologous transplantation and 1 year of brentuximab vedotin (BV) maintenance therapy. She now presents 1 year later with relapsed disease above and below the diaphragm. What treatment would you recommend for this patient? PMID: 31808863 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Complications in pregnant women with sickle cell disease.
Authors: Smith-Whitley K Abstract Pregnancy in women with sickle cell disease (SCD) is associated with increased maternal and fetal morbidity and mortality. Outcomes vary widely owing to methodological limitations of clinical studies, but overall, hypertensive disorders of pregnancy, venothromboembolism, poor fetal growth, and maternal and perinatal mortality are increased globally. Few therapeutic interventions have been explored other than prophylactic and selective transfusion therapy. Unfortunately, existing data are limited, and it remains unclear whether prophylactic use of chronic transfusions will improve p...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Selection of matched unrelated donors moving forward: from HLA allele counting to functional matching.
Authors: Fleischhauer K Abstract Matched unrelated donors (URD) are the most frequent source of stem cells for allogeneic hematopoietic cell transplantation (HCT) to date, with HCT performed mainly under conventional immunosuppression by methotrexate and cyclosporine. In this setting, every single allelic donor-recipient mismatch for HLA-A, -B, -C, -DRB1 (8/8), but not for HLA-DQB1, -DPB1, has a significant negative effect on overall survival (OS). When several 8/8 HLA-matched URD are available, donor age is the most important factor impacting OS. Moving forward from the traditional way of counting the number of do...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Update from the clinic: what's new in the diagnosis of cancer-associated thrombosis?
Authors: Peterson EA, Lee AYY Abstract Malignancy is associated with a high risk of venous thromboembolism (VTE), and treatment with anticoagulant therapy is associated with a high risk of bleeding. Thus, accurate and timely VTE diagnosis in cancer patients is essential for identifying individuals who would benefit from anticoagulant therapy and for avoiding unnecessary treatment that can cause anticoagulant-related bleeding. The approach to the diagnosis of VTE in non-cancer patients involves a stepwise process beginning with an assessment of the pretest probability (PTP) of VTE using a validated clinical predicti...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Relapsed disease and aspects of undetectable MRD and treatment discontinuation.
Authors: Eichhorst B, Fürstenau M, Hallek M Abstract Continuous treatment vs fixed duration of monotherapies and combinations of targeted agents are treatment options in relapsed chronic lymphocytic leukemia. The optimal choice of relapse treatment is dependent on the prior frontline therapy, duration of remission after frontline, genetic markers, and patients' condition, including age and comorbidities. Combination therapies may result in deep responses with undetectable minimal residual disease (uMRD). Although uMRD is an excellent predictive marker for disease progression, it is rarely used in clinical prac...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Gene therapy for hemophilia.
This study has been followed by unparalleled advances in gene therapy for hemophilia A and B, leading to clotting factor activity approaching normal or near-normal levels associated with a "zero bleed rates" in previously severely affected patients following a single administration of AAV vectors. Thus, AAV gene therapies are likely to alter the treatment paradigm for hemophilia A and B. This review explores recent progress and the remaining limitations that need to be overcome for wider availability of this novel treatment of inherited bleeding disorders. PMID: 31808868 [PubMed - in process] (Source: Hematol...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Evidence-Based Minireview: Perioperative management of the VWD patient at elevated thrombotic risk.
Authors: Husseinzadeh HD, Haberichter S PMID: 31808869 [PubMed - in process] (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Case-based discussion on the implications of exogenous estrogens in hemostasis and thrombosis: the obstetrician's view.
Authors: James AH Abstract This is the obstetrician's view on 3 different clinical scenarios involving bleeding and thrombotic disorders. In the first scenario, an 18 year old with a history of heavy menstrual bleeding since menarche presents with abdominal pain and ultrasound findings suggestive of a hemorrhagic ovarian cyst. The association with an underlying bleeding disorder is recognized. The goals of management, which are controlling hemorrhage and preserving fertility, are stated. Ovarian suppression, the most effective method to prevent recurrent hemorrhagic ovarian cysts, is outlined. Long-term management ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Update from the laboratory: mechanistic studies of pathways of cancer-associated venous thrombosis using mouse models.
Authors: Hisada Y, Mackman N Abstract Cancer patients have an increased risk of venous thromboembolism (VTE). The rate of VTE varies with cancer type, with pancreatic cancer having one of the highest rates, suggesting that there are cancer type-specific mechanisms of VTE. Risk assessment scores, such as the Khorana score, have been developed to identify ambulatory cancer patients at high risk of VTE. However, the Khorana score performed poorly in discriminating pancreatic cancer patients at risk of VTE. Currently, thromboprophylaxis is not recommended for cancer outpatients. Recent clinical trials showed that facto...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

The growing landscape of FLT3 inhibition in AML.
Authors: Smith CC Abstract Midostaurin and gilteritinib are FLT3 inhibitors that have been recently approved for use in FLT3-mutant acute myeloid leukemia (AML). These approved drugs represent a new standard of care for patients with FLT3 mutations in both the first-line and salvage settings. The success of midostaurin used in combination with induction chemotherapy has prompted exploration of newer, more potent and targeted inhibitors (including gilteritinib) in the first-line setting in combination with chemotherapy. At the same time, the success of gilteritinib and other newer FLT3 inhibitors as monotherapy in t...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Lowering the boom on lower-risk myelodysplastic syndromes.
Authors: Sekeres MA, Patel BJ Abstract Lower-risk myelodysplastic syndromes are defined using prognostic scoring systems that incorporate data on bone marrow blast percentage, degree and numbers of cytopenias, and cytogenetic abnormalities. Increasingly, these are incorporating molecular abnormalities to further refine risk. Therapy is geared toward predominating cytopenias, with erythropoiesis-stimulating agents luspatercept and lenalidomide used to ameliorate anemia, romiplostim and eltrombopag tackling thrombocytopenia, and hypomethylating agents and antithymocyte globulin palliating pancytopenia. Newer agents o...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Management of iron deficiency.
Authors: Ning S, Zeller MP Abstract Iron deficiency (ID) affects billions of people worldwide and remains the leading cause of anemia with significant negative impacts on health. Our approach to ID and iron deficiency anemia (IDA) involves three steps (I3): (1) identification of ID/IDA, (2) investigation of and management of the underlying etiology of ID, and (3) iron repletion. Iron repletion options include oral and intravenous (IV) iron formulations. Oral iron remains a therapeutic option for the treatment of ID in stable patients, but there are many populations for whom IV iron is more effective. Therefore, IV ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Moving immunotherapy into the front line in ALL.
Authors: Winters A, Gore L Abstract Although almost 90% of children with acute lymphoblastic leukemia (ALL) and ∼60% of children with acute myeloid leukemia are cured with frontline therapy, relapse and chemotherapy resistance are significant challenges that contribute to morbidity and mortality. Even with long-term survival, the acute and chronic burdens of therapy are major issues for patients and families. Long-term side effects occur, including cardiac, endocrinologic, neurcognitive, orthopedic, and psychosocial problems, and healthy survivorship is frequently compromised. With goals of minimizing relapse a...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research