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Journals Hematology - the Education Pro...

Hematology - the Education Program of the American Society of Hematology

https://read.qxmd.com/read/38066921/dual-targeted-regimens-for-the-frontline-treatment-of-cll
#21
JOURNAL ARTICLE
Chaitra Ujjani
The treatment landscape of chronic lymphocytic leukemia (CLL) has evolved considerably over the past decade due to the development of effective novel agents with varying mechanisms of action, including Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) inhibitors. Extrapolating upon the success of anti-CD20-directed chemoimmunotherapy, a dual-targeted approach has been explored in treatment-naive patients with CLL. Anti-CD20 monoclonal antibody combinations with BTK inhibitors as well as BCL2 inhibitors have demonstrated superiority over traditional cytotoxic chemoimmunotherapy regimens such as fludarabine, cyclophosphamide, and rituximab; bendamustine-rituximab; and obinutuzumab-chlorambucil...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066920/resistance-mutations-in-cml-and-how-we-approach-them
#22
REVIEW
Simona Soverini
Among the variety of resistance mechanisms that may underlie a non-optimal response to tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia patients, secondary point mutations in the BCR::ABL1 kinase domain (KD) represent the only actionable one. Each of the 5 ATP-competitive inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) has a well-defined spectrum of resistance mutations. Growing clinical experience will soon allow to also elucidate the full spectrum of mutations conferring resistance to asciminib (that appear not to be confined to the myristate binding pocket)...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066919/atypical-cml-diagnosis-and-treatment
#23
JOURNAL ARTICLE
Massimo Breccia
Atypical chronic myeloid leukemia (aCML) is included in the group of myelodysplastic/myeloproliferative neoplasms by the International Consensus Classification and has been renamed as MDS/MPN with neutrophilia by the fifth edition of World Health Organization classification. It is always characterized by morphologic identification of granulocytic dysplasia with >10% circulating immature myeloid cells, 2 distinguished features that differentiate this disease among the others. Somatic mutations may help to diagnose but are not specifically pathognomonic of the disease, with the most detected including ASXL1, SETBP1, NRAS, KRAS, SRSF2, and TET2 and with low-frequency CBL, CSF3R, JAK2, and ETNK1...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066918/acute-lymphoblastic-leukemia-in-young-adults-which-treatment
#24
JOURNAL ARTICLE
Annabelle Anandappa, Emily Curran
Despite improvements in survival among pediatric patients with acute lymphoblastic leukemia (ALL), survival outcomes for adolescents and young adults (AYAs) with ALL have lagged. The reasons for the inferior outcomes among AYAs are multifactorial, each presenting unique challenges and requiring novel solutions. First, adverse disease biology is more common among AYAs with ALL. Ongoing trials are investigating novel approaches to treatment, such as incorporating JAK inhibitors for Philadelphia chromosome-like ALL, menin inhibitors for KMT2A-rearranged ALL, and BCL2/BCLXL inhibition for T-cell ALL...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066917/the-dos-don-ts-and-nuances-of-thrombophilia-testing
#25
JOURNAL ARTICLE
Thita Chiasakul, Kenneth A Bauer
Considerable progress has been made in elucidating genetic and biologic risk factors for venous thromboembolism (VTE). Despite being able to identify heritable defects in a substantial proportion of patients with VTE, testing has not, in general, proven useful in management. Despite efforts to reduce inappropriate testing, it often falls to the hematologist to consult on patients having undergone thrombophilia testing. Through a series of cases, we discuss how D-dimer testing can be helpful in VTE recurrence risk stratification in younger women as well as how to approach patients with persistently elevated D-dimer levels in the absence of thrombosis...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066916/are-transplant-indications-changing-for-myelofibrosis
#26
REVIEW
Jeanne Palmer
Myelofibrosis is a devastating myeloid malignancy characterized by dysregulation of the JAK-STAT pathway, resulting in splenomegaly, constitutional symptoms, anemia, thrombocytopenia, leukocytosis, and an increased likelihood of progression to acute leukemia. The only curative option is allogeneic stem cell transplantation. The numbers of transplants have been increasing every year, and although there have been improvements in survival, there remain many unanswered questions. In this review, we will evaluate patient selection and appropriate timing for transplantation...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066915/understanding-differential-technologies-for-detection-of-mrd-and-how-to-incorporate-into-clinical-practice
#27
JOURNAL ARTICLE
Jacqueline Cloos, Lok Lam Ngai, Michael Heuser
Patient- and leukemia-specific factors assessed at diagnosis classify patients with acute myeloid leukemia (AML) in risk categories that are prognostic for outcome. The induction phase with intensive chemotherapy in fit patients aims to reach a complete remission (CR) of less than 5% blasts in bone marrow by morphology. To deepen and sustain the response, induction is followed by consolidation treatment. This postremission treatment of patients with AML is graduated in intensity based on this favorable, intermediate, or adverse risk group classification as defined in the European Leukemia Network (ELN) 2022 recommendations...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066914/clonal-evolution-in-inherited-marrow-failure-syndromes-predicts-disease-progression
#28
REVIEW
Kristen E Schratz
Progression to myelodysplastic syndromes (MDS) and acute myeloid leukemia is one of the most serious complications of the inherited bone marrow failure and MDS-predisposition syndromes. Given the lack of predictive markers, this risk can also be a source of great uncertainty and anxiety to patients and their providers alike. Recent data show that some acquired mutations may provide a window into this risk. While maladaptive mechanisms, such as monosomy 7, are associated with a high risk of leukemogenesis, mutations that offset the inherited defect (known as somatic genetic rescue) may attenuate this risk...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066913/clonal-hematopoiesis-in-frequent-whole-blood-donors
#29
JOURNAL ARTICLE
Darja Karpova
Healthy volunteer donors are committed to contributing key medical resources. Repeated, regular donation of whole blood represents a specific trigger of hematopoietic stress. Hematopoietic stem cells (HSCs) are known to respond to environmental triggers by altering their differentiation and/or proliferative behavior. This can manifest in long-term changes in the clonal dynamics of HSCs, such as the age-associated expansion of HSCs carrying somatic mutations in genes associated with hematologic cancers-that is, clonal hematopoiesis (CH)...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066912/car-t-cell-therapy-in-aggressive-lymphomas-identifying-prognostic-and-predictive-markers
#30
JOURNAL ARTICLE
Alberto Mussetti, Nicole Fabbri, Anna Sureda
We discuss different pre-infusion, post-infusion and post-CAR T-cell relapse prognostic factors influencing the outcomes of anti-CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphomas. Despite the overall positive results of anti-CD19 CAR T-cell therapy, a significant percentage of patients relapse. We summarize the efforts made to identify predictive factors for response and durable remissions and survival. In the pre-infusion setting, the patient-related factors discussed include Eastern Cooperative Oncology Group performance status, age, and comorbidities...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066911/pyruvate-kinase-activators-targeting-red-cell-metabolism-in-thalassemia
#31
JOURNAL ARTICLE
Kevin H M Kuo
Thalassemia is an inherited red blood cell disorder whereby the qualitative and/or quantitative imbalance in α- to β-globin ratio results in hemolysis and ineffective erythropoiesis. Oxidative stress, from the precipitated excess globin and free iron, is a major factor that drives hemolysis and ineffective erythropoiesis. Pyruvate kinase activity and adenosine triphosphate availability are reduced due to the overwhelmed cellular antioxidant system from the excessive oxidative stress. Mitapivat, a pyruvate kinase activator in development as a treatment for thalassemia, was shown to increase hemoglobin and reduce hemolysis in a small phase 2 single-arm trial of patients with α- and β-thalassemia...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066910/how-to-manage-splanchnic-vein-thrombosis-in-patients-with-liver-disease
#32
REVIEW
Nicoletta Riva, Walter Ageno
Liver cirrhosis and splanchnic vein thrombosis (SVT) are strictly correlated. Portal vein thrombosis, the most common location of SVT, is frequently diagnosed in liver cirrhosis (pooled incidence 4.6 per 100 patient-years), and liver cirrhosis is a common risk factor for SVT (reported in 24%-28% of SVT patients). In cirrhosis-associated SVT, anticoagulant treatment reduces mortality rates, thrombosis extension, and major bleeding, and increases the rates of recanalization, compared to no treatment. Achieving vessel recanalization improves the prognosis of cirrhotic patients by reducing liver-related complications (such as variceal bleeding, ascites, hepatic encephalopathy)...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066909/acute-leukemias-and-complicated-lymphomas-pearls-to-optimize-management-when-patients-stay-local
#33
JOURNAL ARTICLE
Dipti Patel-Donnelly, Mitul Gandhi
Hematologic malignancies often present acutely with a constellation of infectious complications, pancytopenia, tumor lysis, and renal dysfunction. Acute leukemias and aggressive lymphomas often require hospitalization for rapid diagnostic evaluation, urgent management of complicating presentations, and timely management of intensive systemic therapies. There is an emerging paradigm whereby complex cancer care can be safely and effectively provided in the community, where the majority of cancer is treated. A substantive and effective network between local oncologists and their academic counterparts will enhance care for the patient, advance research, and help bring complicated therapies to local centers, thereby improving access...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066908/management-of-aggressive-lymphoma-after-car-t-cell-therapy-failure
#34
REVIEW
Loretta J Nastoupil, Swetha Kambhampati
Several recent advances have affected the treatment landscape of diffuse large B-cell lymphoma. Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of chemorefractory disease. Two randomized studies in early relapse disease have expanded the label to provide access to CAR T-cell therapy as early as second line for some patients. Despite the durable remissions that have been achieved, many patients will experience relapse. There is a growing population of patients previously treated with CAR T-cell therapy facing dismal outcomes...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066907/selection-of-bispecific-antibody-therapies-or-car-t-cell-therapy-in-relapsed-lymphomas
#35
REVIEW
Ajay Major, Manali Kamdar
Patients with relapsed and refractory (R/R) aggressive B-cell non-Hodgkin lymphomas have historically poor survival outcomes, with chimeric antigen receptor T-cell (CAR-T) therapy now presenting a curative option for a subset of those patients. However, with the approval of several novel bispecific monoclonal antibody (BsAb) therapies with considerable activity in R/R aggressive large B-cell lymphomas (LBCL), patients and oncologists will be faced with decisions regarding how to sequence CAR-T and BsAb therapies based on patient- and disease-related factors...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066906/the-optimal-management-of-relapsed-and-refractory-hodgkin-lymphoma-post-brentuximab-and-checkpoint-inhibitor-failure
#36
JOURNAL ARTICLE
Natalie S Grover, Christopher Dittus, Astha Thakkar, Anne W Beaven
The treatment landscape of classical Hodgkin lymphoma has changed dramatically over the past decade. Relapsed and refractory mainstay therapeutics such as brentuximab vedotin (BV) and checkpoint inhibitors (CPIs) are being moved to earlier lines of therapy. However, the treatment of patients who progress after BV and CPI remains a challenge. Allogeneic stem cell transplantation still plays an important role in this patient population as the only current treatment approach with curative potential. Unfortunately, not all patients are transplant candidates, and many will still relapse afterward...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066905/using-disease-modifying-therapies-in-sickle-cell-disease
#37
JOURNAL ARTICLE
Parul Rai, Kenneth I Ataga
As curative therapy using allogeneic hematopoietic stem cell transplantation as well as gene therapy and gene editing remains inaccessible to most patients with sickle cell disease, the availability of drug therapies that are safe, efficacious, and affordable is highly desirable. Increasing progress is being made in developing drug therapies based on our understanding of disease pathophysiology. Four drugs, hydroxyurea, L-glutamine, crizanlizumab, and voxelotor, are currently approved by the US Food and Drug Administration, with multiple others at various stages of testing...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066904/how-to-diagnose-and-manage-antiphospholipid-syndrome
#38
REVIEW
Anne Hubben, Keith R McCrae
Antiphospholipid antibodies (aPL) are autoimmune antibodies directed toward phospholipids or phospholipid-protein complexes, particularly those containing β2-glycoprotein I (β2GPI). Persistently positive aPL accompanied by arterial or venous thrombosis, or recurrent pregnancy loss, constitutes the antiphospholipid syndrome (APS). Several types of aPL with different specificities have been defined and may be detected in the clinical lab, including lupus anticoagulants (detected using clotting assays) and anticardiolipin, anti-β2GPI and anti-prothrombin/phosphatidylserine antibodies (detected by ELISA); each of the last 3 aPL may be either IgG, IgM, or IgA, though IgA antibodies are not included in criteria for APS...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066903/should-older-patients-with-low-weight-and-ckd-receive-full-dose-doacs-for-treatment-of-acute-proximal-dvt
#39
JOURNAL ARTICLE
Nicolas Gallastegui, Camila Masias
No abstract text is available yet for this article.
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066902/long-term-follow-up-of-cd19-car-t-cell-therapy-in-children-and-young-adults-with-b-all
#40
JOURNAL ARTICLE
Rebecca Epperly, Nirali N Shah
The tremendous successes of CD19-directed CAR T cells in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) has led to the more widespread use of this important treatment modality. With an ability to induce remission and potentially lead to long-term survival in patients with multiply relapsed/chemotherapy refractory disease, more children are now receiving this therapy with the hope of inducing a long-term durable remission (with or without consolidative hematopoietic cell transplantation)...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
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