Selection of bispecific antibody therapies or CAR-T cell therapy in relapsed lymphomas
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):370-381. doi: 10.1182/hematology.2023000438.ABSTRACTPatients 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 b...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Ajay Major Manali Kamdar Source Type: research
Management of aggressive lymphoma after CAR T-cell therapy failure
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):364-369. doi: 10.1182/hematology.2023000437.ABSTRACTSeveral 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 C...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Loretta J Nastoupil Swetha Kambhampati Source Type: research
Acute leukemias and complicated lymphomas: pearls to optimize management when patients stay local
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):311-317. doi: 10.1182/hematology.2023000430.ABSTRACTHematologic 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 substa...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Dipti Patel-Donnelly Mitul Gandhi Source Type: research
How to manage splanchnic vein thrombosis in patients with liver disease
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):281-288. doi: 10.1182/hematology.2023000481.ABSTRACTLiver 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 vesse...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Nicoletta Riva Walter Ageno Source Type: research
Pyruvate kinase activators: targeting red cell metabolism in thalassemia
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):114-120. doi: 10.1182/hematology.2023000468.ABSTRACTThalassemia 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...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Kevin H M Kuo Source Type: research
CAR T-cell therapy in aggressive lymphomas-identifying prognostic and predictive markers
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):357-363. doi: 10.1182/hematology.2023000436.ABSTRACTWe 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 ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Alberto Mussetti Nicole Fabbri Anna Sureda Source Type: research
Clonal hematopoiesis in frequent whole blood donors
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):299-304. doi: 10.1182/hematology.2023000483.ABSTRACTHealthy 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, clo...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Darja Karpova Source Type: research
Clonal evolution in inherited marrow failure syndromes predicts disease progression
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):125-134. doi: 10.1182/hematology.2023000469.ABSTRACTProgression 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, mutation...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Kristen E Schratz Source Type: research
Understanding differential technologies for detection of MRD and how to incorporate into clinical practice
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):682-690. doi: 10.1182/hematology.2023000454.ABSTRACTPatient- 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, intermedia...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Jacqueline Cloos Lok Lam Ngai Michael Heuser Source Type: research
Are transplant indications changing for myelofibrosis?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):676-681. doi: 10.1182/hematology.2023000453.ABSTRACTMyelofibrosis 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 patie...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Jeanne Palmer Source Type: research
The dos, don'ts, and nuances of thrombophilia testing
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):593-599. doi: 10.1182/hematology.2023000491.ABSTRACTConsiderable 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 ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Thita Chiasakul Kenneth A Bauer Source Type: research
Acute lymphoblastic leukemia in young adults: which treatment?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):587-592. doi: 10.1182/hematology.2023000512.ABSTRACTDespite 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, ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Annabelle Anandappa Emily Curran Source Type: research
Atypical CML: diagnosis and treatment
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):476-482. doi: 10.1182/hematology.2023000448.ABSTRACTAtypical 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 diagno...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Massimo Breccia Source Type: research
Resistance mutations in CML and how we approach them
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):469-475. doi: 10.1182/hematology.2023000447.ABSTRACTAmong 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 resi...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Simona Soverini Source Type: research
Dual-targeted regimens for the frontline treatment of CLL
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):421-426. doi: 10.1182/hematology.2023000506.ABSTRACTThe 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 hav...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Chaitra Ujjani Source Type: research
